Arterial Suture in Acute Radiation Sickness - USSR

DTIC Science & Technology

1960-06-30

was surrounded, in the area of the suture, by abundantly developed cicatrical tissue and was tightly adhered to the surrounding tissue. When there...later, the vascular cicatrix represents solid cicatrical tissue, and, on the side of the vascular lumen, is covered with endothelim, Silk threads were

Angiogenesis in tissue engineering: from concept to the vascularization of scaffold construct

NASA Astrophysics Data System (ADS)

Amirah Ishak, Siti; Pangestu Djuansjah, J. R.; Kadir, M. R. Abdul; Sukmana, Irza

2014-06-01

Angiogenesis, the formation of micro-vascular network from the preexisting vascular vessels, has been studied in the connection to the normal developmental process as well as numerous diseases. In tissue engineering research, angiogenesis is also essential to promote micro-vascular network inside engineered tissue constructs, mimicking a functional blood vessel in vivo. Micro-vascular network can be used to maintain adequate tissue oxygenation, nutrient transfer and waste removal. One of the problems faced by angiogenesis researchers is to find suitable in vitro assays and methods for assessing the effect of regulators on angiogenesis and micro-vessel formation. The assay would be reliable and repeatable with easily quantifiable with physiologically relevant. This review aims to highlights recent advanced and future challenges in developing and using an in vitro angiogenesis assay for the application on biomedical and tissue engineering research.

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

PubMed Central

Nguyen, Lonnissa H.; Annabi, Nasim; Nikkhah, Mehdi; Bae, Hojae; Binan, Loïc; Park, Sangwon; Kang, Yunqing

2012-01-01

Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes. PMID:22765012

WOX4 and WOX14 act downstream of the PXY receptor kinase to regulate plant vascular proliferation independently of any role in vascular organisation.

PubMed

Etchells, J Peter; Provost, Claire M; Mishra, Laxmi; Turner, Simon R

2013-05-01

In plants, the cambium and procambium are meristems from which vascular tissue is derived. In contrast to most plant cells, stem cells within these tissues are thin and extremely long. They are particularly unusual as they divide down their long axis in a highly ordered manner, parallel to the tangential axis of the stem. CLAVATA3-LIKE/ESR-RELATED 41 (CLE41) and PHLOEM INTERCALATED WITH XYLEM (PXY) are a multifunctional ligand-receptor pair that regulate vascular cell division, vascular organisation and xylem differentiation in vascular tissue. A transcription factor gene, WUSCHEL HOMEOBOX RELATED 4 (WOX4) has been shown to act downstream of PXY. Here we show that WOX4 acts redundantly with WOX14 in the regulation of vascular cell division, but that these genes have no function in regulating vascular organisation. Furthermore, we identify an interaction between PXY and the receptor kinase ERECTA (ER) that affects the organisation of the vascular tissue but not the rate of cell division, suggesting that cell division and vascular organisation are genetically separable. Our observations also support a model whereby tissue organisation and cell division are integrated via PXY and ER signalling, which together coordinate development of different cell types that are essential for normal stem formation.

Vascularization strategies for tissue engineers.

PubMed

Dew, Lindsey; MacNeil, Sheila; Chong, Chuh Khiun

2015-01-01

All tissue-engineered substitutes (with the exception of cornea and cartilage) require a vascular network to provide the nutrient and oxygen supply needed for their survival in vivo. Unfortunately the process of vascular ingrowth into an engineered tissue can take weeks to occur naturally and during this time the tissues become starved of essential nutrients, leading to tissue death. This review initially gives a brief overview of the processes and factors involved in the formation of new vasculature. It then summarizes the different approaches that are being applied or developed to overcome the issue of slow neovascularization in a range of tissue-engineered substitutes. Some potential future strategies are then discussed.

Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in vivo.

PubMed

Proulx, Steven T; Luciani, Paola; Alitalo, Annamari; Mumprecht, Viviane; Christiansen, Ailsa J; Huggenberger, Reto; Leroux, Jean-Christophe; Detmar, Michael

2013-07-01

Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice with overexpression of vascular endothelial growth factors VEGF-A or -C. Near-infrared dye conjugates were developed to identify a suitable vascular tracer that had a prolonged circulation lifetime and slow leakage into normal tissue after intravenous injection. Dynamic simultaneous imaging of ear skin and a large blood vessel in the leg enabled determination of the intravascular signal (blood volume fraction) from the tissue signal shortly after injection and quantifications of vascular leakage into the extravascular tissue over time. This method allowed for the sensitive detection of increased blood vascularity and leakage rates in K14-VEGF-A transgenic mice and also reliably measured inflammation-induced changes of vascularity and leakage over time in the same mice. Measurements after injection of recombinant VEGF-A surprisingly revealed increased blood vascular leakage and lymphatic clearance in K14-VEGF-C transgenic mice which have an expanded cutaneous lymphatic vessel network, potentially indicating unanticipated effects of lymphatic drainage on vascular leakage. Increased vascular leakage was also detected in subcutaneous tumors, confirming that the method can also be applied to deeper tissues. This new imaging method might facilitate longitudinal investigations of the in vivo effects of drug candidates, including angiogenesis inhibitors, in preclinical disease models.

Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in vivo

PubMed Central

Proulx, Steven T.; Luciani, Paola; Alitalo, Annamari; Mumprecht, Viviane; Christiansen, Ailsa J.; Huggenberger, Reto

2013-01-01

Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice with overexpression of vascular endothelial growth factors VEGF-A or -C. Near-infrared dye conjugates were developed to identify a suitable vascular tracer that had a prolonged circulation lifetime and slow leakage into normal tissue after intravenous injection. Dynamic simultaneous imaging of ear skin and a large blood vessel in the leg enabled determination of the intravascular signal (blood volume fraction) from the tissue signal shortly after injection and quantifications of vascular leakage into the extravascular tissue over time. This method allowed for the sensitive detection of increased blood vascularity and leakage rates in K14-VEGF-A transgenic mice and also reliably measured inflammation-induced changes of vascularity and leakage over time in the same mice. Measurements after injection of recombinant VEGF-A surprisingly revealed increased blood vascular leakage and lymphatic clearance in K14-VEGF-C transgenic mice which have an expanded cutaneous lymphatic vessel network, potentially indicating unanticipated effects of lymphatic drainage on vascular leakage. Increased vascular leakage was also detected in subcutaneous tumors, confirming that the method can also be applied to deeper tissues. This new imaging method might facilitate longitudinal investigations of the in vivo effects of drug candidates, including angiogenesis inhibitors, in preclinical disease models. PMID:23325334

In Vitro Engineering of Vascularized Tissue Surrogates

PubMed Central

Sakaguchi, Katsuhisa; Shimizu, Tatsuya; Horaguchi, Shigeto; Sekine, Hidekazu; Yamato, Masayuki; Umezu, Mitsuo; Okano, Teruo

2013-01-01

In vitro scaling up of bioengineered tissues is known to be limited by diffusion issues, specifically a lack of vasculature. Here, we report a new strategy for preserving cell viability in three-dimensional tissues using cell sheet technology and a perfusion bioreactor having collagen-based microchannels. When triple-layer cardiac cell sheets are incubated within this bioreactor, endothelial cells in the cell sheets migrate to vascularize in the collagen gel, and finally connect with the microchannels. Medium readily flows into the cell sheets through the microchannels and the newly developed capillaries, while the cardiac construct shows simultaneous beating. When additional triple-layer cell sheets are repeatedly layered, new multi-layer construct spontaneously integrates and the resulting construct becomes a vascularized thick tissue. These results confirmed our method to fabricate in vitro vascularized tissue surrogates that overcomes engineered-tissue thickness limitations. The surrogates promise new therapies for damaged organs as well as new in vitro tissue models. PMID:23419835

Stem cell function during plant vascular development

PubMed Central

Miyashima, Shunsuke; Sebastian, Jose; Lee, Ji-Young; Helariutta, Yka

2013-01-01

The plant vascular system, composed of xylem and phloem, evolved to connect plant organs and transport various molecules between them. During the post-embryonic growth, these conductive tissues constitutively form from cells that are derived from a lateral meristem, commonly called procambium and cambium. Procambium/cambium contains pluripotent stem cells and provides a microenvironment that maintains the stem cell population. Because vascular plants continue to form new tissues and organs throughout their life cycle, the formation and maintenance of stem cells are crucial for plant growth and development. In this decade, there has been considerable progress in understanding the molecular control of the organization and maintenance of stem cells in vascular plants. Noticeable advance has been made in elucidating the role of transcription factors and major plant hormones in stem cell maintenance and vascular tissue differentiation. These studies suggest the shared regulatory mechanisms among various types of plant stem cell pools. In this review, we focus on two aspects of stem cell function in the vascular cambium, cell proliferation and cell differentiation. PMID:23169537

Engineering Pre-vascularized Scaffolds for Bone Regeneration.

PubMed

Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

2015-01-01

Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.

The Populus class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems.

PubMed

Robischon, Marcel; Du, Juan; Miura, Eriko; Groover, Andrew

2011-03-01

The secondary growth of a woody stem requires the formation of a vascular cambium at an appropriate position and proper patterning of the vascular tissues derived from the cambium. Class III homeodomain-leucine zipper (HD ZIP) transcription factors have been implicated in polarity determination and patterning in lateral organs and primary vascular tissues and in the initiation and function of shoot apical meristems. We report here the functional characterization of a Populus class III HD ZIP gene, popREVOLUTA (PRE), that demonstrates another role for class III HD ZIPs in regulating the development of cambia and secondary vascular tissues. PRE is orthologous to Arabidopsis (Arabidopsis thaliana) REVOLUTA and is expressed in both the shoot apical meristem and in the cambial zone and secondary vascular tissues. Transgenic Populus expressing a microRNA-resistant form of PRE presents unstable phenotypic abnormalities affecting both primary and secondary growth. Surprisingly, phenotypic changes include abnormal formation of cambia within cortical parenchyma that can produce secondary vascular tissues in reverse polarity. Genes misexpressed in PRE mutants include transcription factors and auxin-related genes previously implicated in class III HD ZIP functions during primary growth. Together, these results suggest that PRE plays a fundamental role in the initiation of the cambium and in regulating the patterning of secondary vascular tissues.

Computer-aided design of microvasculature systems for use in vascular scaffold production.

PubMed

Mondy, William Lafayette; Cameron, Don; Timmermans, Jean-Pierre; De Clerck, Nora; Sasov, Alexander; Casteleyn, Christophe; Piegl, Les A

2009-09-01

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

PubMed

Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

2016-01-01

The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs

PubMed Central

Bertassoni, Luiz E.; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R.; Yang, Yunzhi; Khademhosseini, Ali

2014-01-01

Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photo cross linkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly (ethylene glycol-co-lactide) acrylate (SPELA), poly (ethylene glycol) dimethacrylate (PEGDMA) and poly (ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip. PMID:24860845

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps.

PubMed

Zhang, Qixu; Johnson, Joshua A; Dunne, Lina W; Chen, Youbai; Iyyanki, Tejaswi; Wu, Yewen; Chang, Edward I; Branch-Brooks, Cynthia D; Robb, Geoffrey L; Butler, Charles E

2016-04-15

Using a perfusion decellularization protocol, we developed a decellularized skin/adipose tissue flap (DSAF) comprising extracellular matrix (ECM) and intact vasculature. Our DSAF had a dominant vascular pedicle, microcirculatory vascularity, and a sensory nerve network and retained three-dimensional (3D) nanofibrous structures well. DSAF, which was composed of collagen and laminin with well-preserved growth factors (e.g., vascular endothelial growth factor, basic fibroblast growth factor), was successfully repopulated with human adipose-derived stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs), which integrated with DSAF and formed 3D aggregates and vessel-like structures in vitro. We used microsurgery techniques to re-anastomose the recellularized DSAF into nude rats. In vivo, the engineered flap construct underwent neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant adipose tissue formation at 3months postoperatively. Our results indicate that DSAF co-cultured with hASCs and HUVECs is a promising platform for vascularized soft tissue flap engineering. This platform is not limited by the flap size, as the entire construct can be immediately perfused by the recellularized vascular network following simple re-integration into the host using conventional microsurgical techniques. Significant soft tissue loss resulting from traumatic injury or tumor resection often requires surgical reconstruction using autologous soft tissue flaps. However, the limited availability of qualitative autologous flaps as well as the donor site morbidity significantly limits this approach. Engineered soft tissue flap grafts may offer a clinically relevant alternative to the autologous flap tissue. In this study, we engineered vascularized soft tissue free flap by using skin/adipose flap extracellular matrix scaffold (DSAF) in combination with multiple types of human cells. Following vascular reanastomosis in the recipient site, the engineered products successful regenerated large-scale fat tissue in vivo. This approach may provide a translatable platform for composite soft tissue free flap engineering for microsurgical reconstruction. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparative physiology of mice and rats: radiometric measurement of vascular parameters in rodent tissues.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Ulufatu, Sheila; Bumbaca, Daniela; Cahaya, Hendry S; Majidy, Nicholas; Van Hoy, Marjie; Schweiger, Michelle G; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A

2014-05-05

A solid understanding of physiology is beneficial in optimizing drug delivery and in the development of clinically predictive models of drug disposition kinetics. Although an abundance of data exists in the literature, it is often confounded by the use of various experimental methods and a lack of consensus in values from different sources. To help address this deficiency, we sought to directly compare three important vascular parameters at the tissue level using the same experimental approach in both mice and rats. Interstitial volume, vascular volume, and blood flow were radiometrically measured in selected harvested tissues of both species by extracellular marker infusion, red blood cell labeling, and rubidium chloride bolus distribution, respectively. The latter two parameters were further compared by whole-body autoradiographic imaging. An overall good interspecies agreement was observed for interstitial volume and blood flow on a weight-normalized basis in most tissues. In contrast, the measured vascular volumes of most rat tissues were higher than for mouse. Mice and rats, the two most commonly utilized rodent species in translational drug development, should not be considered as interchangeable in terms of vascular volume per gram of tissue. This will be particularly critical in biodistribution studies of drugs, as the amount of drug in the residual blood of tissues is often not negligible, especially for biologic drugs (e.g., antibodies) having long circulation half-lives. Physiologically based models of drug pharmacokinetics and/or pharmacodynamics also rely on accurate knowledge of biological parameters in tissues. For tissue parameters with poor interspecies agreement, the significance and possible drivers are discussed.

RhBMP-2 loaded 3D-printed mesoporous silica/calcium phosphate cement porous scaffolds with enhanced vascularization and osteogenesis properties

NASA Astrophysics Data System (ADS)

Li, Cuidi; Jiang, Chuan; Deng, Yuan; Li, Tao; Li, Ning; Peng, Mingzheng; Wang, Jinwu

2017-01-01

A major limitation in the development of effective scaffolds for bone regeneration has been the limited vascularization of the regenerating tissue. Here, we propose the development of a novel calcium phosphate cement (CPC)-based scaffold combining the properties of mesoporous silica (MS) with recombinant human bone morphogenic protein-2 (rhBMP-2) to facilitate vascularization and osteogenesis. Specifically, the development of a custom MS/CPC paste allowed the three-dimensional (3D) printing of scaffolds with a defined macroporous structure and optimized silicon (Si) ions release profile to promote the ingrowth of vascular tissue at an early stage after implantation in support of tissue viability and osteogenesis. In addition, the scaffold microstructure allowed the prolonged release of rhBMP-2, which in turn significantly stimulated the osteogenesis of human bone marrow stromal cells in vitro and of bone regeneration in vivo as shown in a rabbit femur defect repair model. Thus, the combination MS/CPC/rhBMP-2 scaffolds might provide a solution to issues of tissue necrosis during the regeneration process and therefore might be able to be readily developed into a useful tool for bone repair in the clinic.

Cell-microenvironment interactions and architectures in microvascular systems

PubMed Central

Bersini, Simone; Yazdi, Iman K.; Talò, Giuseppe; Shin, Su Ryon; Moretti, Matteo; Khademhosseini, Ali

2016-01-01

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models. PMID:27417066

Cell-microenvironment interactions and architectures in microvascular systems.

PubMed

Bersini, Simone; Yazdi, Iman K; Talò, Giuseppe; Shin, Su Ryon; Moretti, Matteo; Khademhosseini, Ali

2016-11-01

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models. Copyright © 2016 Elsevier Inc. All rights reserved.

Initial evaluation of vascular ingrowth into superporous hydrogels.

PubMed

Keskar, Vandana; Gandhi, Milind; Gemeinhart, Ernest J; Gemeinhart, Richard A

2009-08-01

There is a need for new materials and architectures for tissue engineering and regenerative medicine. Based upon our recent results developing novel scaffold architecture, we hypothesized that this new architecture would foster vascularization, a particular need for tissue engineering. We report on the potential of superporous hydrogel (SPH) scaffolds for in vivo cellular infiltration and vascularization. Poly(ethylene glycol) diacrylate (PEGDA) SPH scaffolds were implanted in the dorsum of severe combined immunodeficient (SCID) mice and harvested after 4 weeks of in vivo implantation. The SPHs were visibly red and vascularized, as apparent when compared to the non-porous hydrogel controls, which were macroscopically avascular. Host cell infiltration was observed throughout the SPHs. Blood cells and vascular structures, confirmed through staining for CD34 and smooth muscle alpha-actin, were observed throughout the scaffolds. This novel soft material may be utilized for cell transplantation, tissue engineering and in combination with cell therapies. The neovasularization and limited fibrotic response suggest that the architecture may be conducive to cell survival and rapid vessel development.

Double-filter identification of vascular-expressed genes using Arabidopsis plants with vascular hypertrophy and hypotrophy.

PubMed

Ckurshumova, Wenzislava; Scarpella, Enrico; Goldstein, Rochelle S; Berleth, Thomas

2011-08-01

Genes expressed in vascular tissues have been identified by several strategies, usually with a focus on mature vascular cells. In this study, we explored the possibility of using two opposite types of altered tissue compositions in combination with a double-filter selection to identify genes with a high probability of vascular expression in early organ primordia. Specifically, we generated full-transcriptome microarray profiles of plants with (a) genetically strongly reduced and (b) pharmacologically vastly increased vascular tissues and identified a reproducible cohort of 158 transcripts that fulfilled the dual requirement of being underrepresented in (a) and overrepresented in (b). In order to assess the predictive value of our identification scheme for vascular gene expression, we determined the expression patterns of genes in two unbiased subsamples. First, we assessed the expression patterns of all twenty annotated transcription factor genes from the cohort of 158 genes and found that seventeen of the twenty genes were preferentially expressed in leaf vascular cells. Remarkably, fifteen of these seventeen vascular genes were clearly expressed already very early in leaf vein development. Twelve genes with published leaf expression patterns served as a second subsample to monitor the representation of vascular genes in our cohort. Of those twelve genes, eleven were preferentially expressed in leaf vascular tissues. Based on these results we propose that our compendium of 158 genes represents a sample that is highly enriched for genes expressed in vascular tissues and that our approach is particularly suited to detect genes expressed in vascular cell lineages at early stages of their inception. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ren; Trindade, Alexandre; Instituto Gulbenkian de Ciencia, Oeiras

Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the densitymore » of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.« less

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix

PubMed Central

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

2015-01-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. PMID:26348142

Comparison of tissue processing methods for microvascular visualization in axolotls.

PubMed

Montoro, Rodrigo; Dickie, Renee

2017-01-01

The vascular system, the pipeline for oxygen and nutrient delivery to tissues, is essential for vertebrate development, growth, injury repair, and regeneration. With their capacity to regenerate entire appendages throughout their lifespan, axolotls are an unparalleled model for vertebrate regeneration, but they lack many of the molecular tools that facilitate vascular imaging in other animal models. The determination of vascular metrics requires high quality image data for the discrimination of vessels from background tissue. Quantification of the vasculature using perfused, cleared specimens is well-established in mammalian systems, but has not been widely employed in amphibians. The objective of this study was to optimize tissue preparation methods for the visualization of the microvascular network in axolotls, providing a basis for the quantification of regenerative angiogenesis. To accomplish this aim, we performed intracardiac perfusion of pigment-based contrast agents and evaluated aqueous and non-aqueous clearing techniques. The methods were verified by comparing the quality of the vascular images and the observable vascular density across treatment groups. Simple and inexpensive, these tissue processing techniques will be of use in studies assessing vascular growth and remodeling within the context of regeneration. Advantages of this method include: •Higher contrast of the vasculature within the 3D context of the surrounding tissue •Enhanced detection of microvasculature facilitating vascular quantification •Compatibility with other labeling techniques.

Scaffolding for Three-Dimensional Embryonic Vasculogenesis

NASA Astrophysics Data System (ADS)

Kraehenbuehl, Thomas P.; Aday, Sezin; Ferreira, Lino S.

Biomaterial scaffolds have great potential to support efficient vascular differentiation of embryonic stem cells. Vascular cell fate-specific biochemical and biophysical cues have been identified and incorporated into three-dimensional (3D) biomaterials to efficiently direct embryonic vasculogenesis. The resulting vascular-like tissue can be used for regenerative medicine applications, further elucidation of biophysical and biochemical cues governing vasculogenesis, and drug discovery. In this chapter, we give an overview on the following: (1) developmental cues for directed differentiation of human embryonic stem cells (hESCs) into vascular cells, (2) 3D vascular differentiation in embryoid bodies (EBs), (3) preparation of 3D scaffolds for the vascular differentiation of hESCs, and (4) the most significant studies combining scaffolding and hESCs for development of vascular-like tissue.

Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sevostyanova, V. V., E-mail: sevostyanova.victoria@gmail.com; Khodyrevskaya, Y. I.; Glushkova, T. V.

The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as amore » scaffold for tissue-engineered vascular grafts.« less

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

PubMed

Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

PubMed Central

Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

2013-01-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals. PMID:23213032

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

PubMed

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

2015-11-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. We reported a method for preparing autologous extracellular matrix scaffolds, murine collagen-Ph hydrogels, and demonstrated its suitability for use in supporting human progenitor cell-based formation of 3D vascular networks in vitro and in vivo. Results showed extensive human vascular networks can be generated within 7 days, engineered vascular density inside collagen-Ph constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with existing vasculature to further support the survival of host muscle tissues. Moreover, optimized conditions of cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Model development and experimental validation for analyzing initial transients of irradiation of tissues during thermal therapy using short pulse lasers.

PubMed

Ganguly, Mohit; Miller, Stephanie; Mitra, Kunal

2015-11-01

Short pulse lasers with pulse durations in the range of nanoseconds and shorter are effective in the targeted delivery of heat energy for precise tissue heating and ablation. This photothermal therapy is useful where the removal of cancerous tissue sections is required. The objective of this paper is to use finite element modeling to demonstrate the differences in the thermal response of skin tissue to short-pulse and continuous wave laser irradiation in the initial stages of the irradiation. Models have been developed to validate the temperature distribution and heat affected zone during laser irradiation of excised rat skin samples and live anesthetized mouse tissue. Excised rat skin samples and live anesthetized mice were subjected to Nd:YAG pulsed laser (1,064 nm, 500 ns) irradiation of varying powers. A thermal camera was used to measure the rise in surface temperature as a result of the laser irradiation. Histological analyses of the heat affected zone created in the tissue samples due to the temperature rise were performed. The thermal interaction of the laser with the tissue was quantified by measuring the thermal dose delivered by the laser. Finite element geometries of three-dimensional tissue sections for continuum and vascular models were developed using COMSOL Multiphysics. Blood flow was incorporated into the vascular model to mimic the presence of discrete blood vessels and contrasted with the continuum model without blood perfusion. The temperature rises predicted by the continuum and the vascular models agreed with the temperature rises observed at the surface of the excised rat tissue samples and live anesthetized mice due to laser irradiation respectively. The vascular model developed was able to predict the cooling produced by the blood vessels in the region where the vessels were present. The temperature rise in the continuum model due to pulsed laser irradiation was higher than that due to continuous wave (CW) laser irradiation in the initial stages of the irradiation. The temperature rise due to pulsed and CW laser irradiation converged as the time of irradiation increased. A similar trend was observed when comparing the thermal dose for pulsed and CW laser irradiation in the vascular model. Finite element models (continuum and vascular) were developed that can be used to predict temperature rise and quantify the thermal dose resulting from laser irradiation of excised rat skin samples and live anesthetized mouse tissue. The vascular model incorporating blood perfusion effects predicted temperature rise better in the live animal tissue. The models developed demonstrated that pulsed lasers caused greater temperature rise and delivered a greater thermal dose than CW lasers of equal average power, especially during the initial transients of irradiation. This analysis will be beneficial for thermal therapy applications where maximum delivery of thermal dose over a short period of time is important. © 2015 Wiley Periodicals, Inc.

Vitamins E and C - effects on matrix components in the vascular system

USDA-ARS?s Scientific Manuscript database

The connective tissue in the vascular system, consisting mainly of vascular smooth muscle cells (VSMC) and the interstitial extracellular matrix (ECM), plays important roles in the maintenance of an intact vascular wall as well as in the repair of atherosclerotic lesions during disease development. ...

Cardiovascular Bio-Engineering: Current State of the Art.

PubMed

Simon-Yarza, Teresa; Bataille, Isabelle; Letourneur, Didier

2017-04-01

Despite the introduction of new drugs and innovative devices contributing in the last years to improve patients' quality of life, morbidity and mortality from cardiovascular diseases remain high. There is an urgent need for addressing the underlying problem of the loss of cardiac or vascular tissues and therefore developing new therapies. Autologous vascular transplants are often limited by poor quality of donor sites and heart organ transplantation by donor shortage. Vascular and cardiac tissue engineering, whose aim is to repair or replace cardiovascular tissues by the use of cells, engineering and materials, as well as biochemical and physicochemical factors, appears in this scenario as a promising tool to repair the damaged hearts and vessels. We will present a general overview on the fundamentals in the area of cardiac and vascular tissue engineering as well as on the latest progresses and challenges.

Embryonic exposure to sodium arsenite perturbs vascular development in zebrafish.

PubMed

McCollum, Catherine W; Hans, Charu; Shah, Shishir; Merchant, Fatima A; Gustafsson, Jan-Åke; Bondesson, Maria

2014-07-01

Exposure to arsenic in its inorganic form, arsenite, causes adverse effects to many different organs and tissues. Here, we have investigated arsenite-induced adverse effects on vascular tissues in the model organism zebrafish, Danio rerio. Zebrafish embryos were exposed to arsenite at different exposure windows and the susceptibility to vascular tissue damage was recorded at 72hours post fertilization (hpf). Intersegmental vessel sprouting and growth was most perturbed by exposure to arsenite during the 24-48hpf window, while disruption in the condensation of the caudal vein plexus was more often observed at the 48-72hpf exposure window, reflecting when these structures develop during normal embryogenesis. The vascular growth rate was decreased by arsenite exposure, and deviated from that of control embryos at around 24-26.5hpf. We further mapped changes in expression of key regulators of angiogenesis and vasculogenesis. Downregulation of vascular endothelial growth factor receptor 1/fms-related tyrosine kinase 1 (vegfr1/flt1) expression was evident already at 24hpf, coinciding with the decreased vascular growth rate. At later time points, matrix metalloproteinase 9 (mmp9) expression was upregulated, suggesting that arsenite affects the composition of the extracellular matrix. In total, the expression of eight key factors involved in different aspects of vascularization was significantly altered by arsenic exposure. In conclusion, our results show that arsenite is a potent vascular disruptor in the developing zebrafish embryo, a finding that calls for an evaluation of arsenite as a developmental vascular toxicant in mammalian model systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamics of vascular branching morphogenesis: The effect of blood and tissue flow

NASA Astrophysics Data System (ADS)

Nguyen, Thi-Hanh; Eichmann, Anne; Le Noble, Ferdinand; Fleury, Vincent

2006-06-01

Vascularization of embryonic organs or tumors starts from a primitive lattice of capillaries. Upon perfusion, this lattice is remodeled into branched arteries and veins. Adaptation to mechanical forces is implied to play a major role in arterial patterning. However, numerical simulations of vessel adaptation to haemodynamics has so far failed to predict any realistic vascular pattern. We present in this article a theoretical modeling of vascular development in the yolk sac based on three features of vascular morphogenesis: the disconnection of side branches from main branches, the reconnection of dangling sprouts (“dead ends”), and the plastic extension of interstitial tissue, which we have observed in vascular morphogenesis. We show that the effect of Poiseuille flow in the vessels can be modeled by aggregation of random walkers. Solid tissue expansion can be modeled by a Poiseuille (parabolic) deformation, hence by deformation under hits of random walkers. Incorporation of these features, which are of a mechanical nature, leads to realistic modeling of vessels, with important biological consequences. The model also predicts the outcome of simple mechanical actions, such as clamping of vessels or deformation of tissue by the presence of obstacles. This study offers an explanation for flow-driven control of vascular branching morphogenesis.

Global transcriptome analysis reveals extensive gene remodeling, alternative splicing and differential transcription profiles in non-seed vascular plant Selaginella moellendorffii.

PubMed

Zhu, Yan; Chen, Longxian; Zhang, Chengjun; Hao, Pei; Jing, Xinyun; Li, Xuan

2017-01-25

Selaginella moellendorffii, a lycophyte, is a model plant to study the early evolution and development of vascular plants. As the first and only sequenced lycophyte to date, the genome of S. moellendorffii revealed many conserved genes and pathways, as well as specialized genes different from flowering plants. Despite the progress made, little is known about long noncoding RNAs (lncRNA) and the alternative splicing (AS) of coding genes in S. moellendorffii. Its coding gene models have not been fully validated with transcriptome data. Furthermore, it remains important to understand whether the regulatory mechanisms similar to flowering plants are used, and how they operate in a non-seed primitive vascular plant. RNA-sequencing (RNA-seq) was performed for three S. moellendorffii tissues, root, stem, and leaf, by constructing strand-specific RNA-seq libraries from RNA purified using RiboMinus isolation protocol. A total of 176 million reads (44 Gbp) were obtained from three tissue types, and were mapped to S. moellendorffii genome. By comparing with 22,285 existing gene models of S. moellendorffii, we identified 7930 high-confidence novel coding genes (a 35.6% increase), and for the first time reported 4422 lncRNAs in a lycophyte. Further, we refined 2461 (11.0%) of existing gene models, and identified 11,030 AS events (for 5957 coding genes) revealed for the first time for lycophytes. Tissue-specific gene expression with functional implication was analyzed, and 1031, 554, and 269 coding genes, and 174, 39, and 17 lncRNAs were identified in root, stem, and leaf tissues, respectively. The expression of critical genes for vascular development stages, i.e. formation of provascular cells, xylem specification and differentiation, and phloem specification and differentiation, was compared in S. moellendorffii tissues, indicating a less complex regulatory mechanism in lycophytes than in flowering plants. The results were further strengthened by the evolutionary trend of seven transcription factor families related to vascular development, which was observed among four representative species of seed and non-seed vascular plants, and nonvascular land and aquatic plants. The deep RNA-seq study of S. moellendorffii discovered extensive new gene contents, including novel coding genes, lncRNAs, AS events, and refined gene models. Compared to flowering vascular plants, S. moellendorffii displayed a less complexity in both gene structure, alternative splicing, and regulatory elements of vascular development. The study offered important insight into the evolution of vascular plants, and the regulation mechanism of vascular development in a non-seed plant.

Bioprinting for vascular and vascularized tissue biofabrication.

PubMed

Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

2017-03-15

Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision, which holds a great promise in fabrication of vascular or vascularized tissues for transplantation use. Although a great progress has recently been made on building perfusable tissues and branched vascular network, a comprehensive review on the state-of-the-art in vascular and vascularized tissue bioprinting has not reported so far. This contribution is thus significant because it discusses the use of three major bioprinting modalities in vascular tissue biofabrication for the first time in the literature and compares their strengths and limitations in details. Moreover, the use of scaffold-based and scaffold-free bioprinting is expounded within the domain of vascular tissue fabrication. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The development and endocrine functions of adipose tissue

USDA-ARS?s Scientific Manuscript database

White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body’s fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and...

Insulin resistance, metabolic stress, and atherosclerosis

PubMed Central

Pansuria, Meghana; Xi, Hang; Li, Le; Yang, Xiao-Feng; Wang, Hong

2012-01-01

Atherosclerosis, a pathological process that underlies the development of cardiovascular disease, is the primary cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia and insulin resistance (IR), in which target tissues fail to respond to insulin. Systemic IR is associated with impaired insulin signaling in the metabolic tissues and vasculature. Insulin receptor is highly expressed in the liver, muscle, pancreas, and adipose tissue. It is also expressed in vascular cells. It has been suggested that insulin signaling in vascular cells regulates cell proliferation and vascular function. In this review, we discuss the association between IR, metabolic stress, and atherosclerosis with focus on 1) tissue and cell distribution of insulin receptor and its differential signaling transduction and 2) potential mechanism of insulin signaling impairment and its role in the development of atherosclerosis and vascular function in metabolic disorders including hyperglycemia, hypertension, dyslipidemia, and hyperhomocysteinemia. We propose that insulin signaling impairment is the foremost biochemical mechanism underlying increased cardiovascular morbidity and mortality in atherosclerosis, T2DM, and metabolic syndrome. PMID:22202099

Whole Organ Tissue Vascularization: Engineering the Tree to Develop the Fruits.

PubMed

Pellegata, Alessandro F; Tedeschi, Alfonso M; De Coppi, Paolo

2018-01-01

Tissue engineering aims to regenerate and recapitulate a tissue or organ that has lost its function. So far successful clinical translation has been limited to hollow organs in which rudimental vascularization can be achieved by inserting the graft into flaps of the omentum or muscle fascia. This technique used to stimulate vascularization of the graft takes advantage of angiogenesis from existing vascular networks. Vascularization of the engineered graft is a fundamental requirement in the process of engineering more complex organs, as it is crucial for the efficient delivery of nutrients and oxygen following in-vivo implantation. To achieve vascularization of the organ many different techniques have been investigated and exploited. The most promising results have been obtained by seeding endothelial cells directly into decellularized scaffolds, taking advantage of the channels remaining from the pre-existing vascular network. Currently, the main hurdle we need to overcome is achieving a fully functional vascular endothelium, stable over a long time period of time, which is engineered using a cell source that is clinically suitable and can generate, in vitro , a yield of cells suitable for the engineering of human sized organs. This review will give an overview of the approaches that have recently been investigated to address the issue of vascularization in the field of tissue engineering of whole organs, and will highlight the current caveats and hurdles that should be addressed in the future.

Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

PubMed

Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

2017-08-17

Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

PubMed Central

Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

2017-01-01

Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

Towards organ printing: engineering an intra-organ branched vascular tree.

PubMed

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2010-03-01

Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a 'built in' intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a 'built in' intra-organ branched vascular tree.

Vascular Mechanobiology: Towards Control of In Situ Regeneration

PubMed Central

van Haaften, Eline E.; Bouten, Carlijn V. C.; Kurniawan, Nicholas A.

2017-01-01

The paradigm of regenerative medicine has recently shifted from in vitro to in situ tissue engineering: implanting a cell-free, biodegradable, off-the-shelf available scaffold and inducing the development of functional tissue by utilizing the regenerative potential of the body itself. This approach offers a prospect of not only alleviating the clinical demand for autologous vessels but also circumventing the current challenges with synthetic grafts. In order to move towards a hypothesis-driven engineering approach, we review three crucial aspects that need to be taken into account when regenerating vessels: (1) the structure-function relation for attaining mechanical homeostasis of vascular tissues; (2) the environmental cues governing cell function; and (3) the available experimental platforms to test instructive scaffolds for in situ tissue engineering. The understanding of cellular responses to environmental cues leads to the development of computational models to predict tissue formation and maturation, which are validated using experimental platforms recapitulating the (patho)physiological micro-environment. With the current advances, a progressive shift is anticipated towards a rational and effective approach of building instructive scaffolds for in situ vascular tissue regeneration. PMID:28671618

Vascular Mechanobiology: Towards Control of In Situ Regeneration.

PubMed

van Haaften, Eline E; Bouten, Carlijn V C; Kurniawan, Nicholas A

2017-07-03

The paradigm of regenerative medicine has recently shifted from in vitro to in situ tissue engineering: implanting a cell-free, biodegradable, off-the-shelf available scaffold and inducing the development of functional tissue by utilizing the regenerative potential of the body itself. This approach offers a prospect of not only alleviating the clinical demand for autologous vessels but also circumventing the current challenges with synthetic grafts. In order to move towards a hypothesis-driven engineering approach, we review three crucial aspects that need to be taken into account when regenerating vessels: (1) the structure-function relation for attaining mechanical homeostasis of vascular tissues, (2) the environmental cues governing cell function, and (3) the available experimental platforms to test instructive scaffolds for in situ tissue engineering. The understanding of cellular responses to environmental cues leads to the development of computational models to predict tissue formation and maturation, which are validated using experimental platforms recapitulating the (patho)physiological micro-environment. With the current advances, a progressive shift is anticipated towards a rational and effective approach of building instructive scaffolds for in situ vascular tissue regeneration.

[Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

PubMed

Arens, C; Glanz, H; Voigt-Zimmermann, S

2015-11-01

The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

Towards organ printing: engineering an intra-organ branched vascular tree

PubMed Central

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2013-01-01

Importance of the field Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. Areas covered in this review We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. What the reader will gain The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. Take home message It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a ‘built in’ intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a ‘built in’ intra-organ branched vascular tree. PMID:20132061

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

PubMed Central

Gravesen, Eva; Lerche Mace, Maria; Nordholm, Anders; Hofman-Bang, Jacob; Hruska, Keith; Haagen Nielsen, Carsten; Kjær, Andreas; Olgaard, Klaus

2018-01-01

Hyperphosphatemia and vascular calcification are frequent complications of chronic renal failure and bone morphogenetic protein 7 (BMP7) has been shown to protect against development of vascular calcification in uremia. The present investigation examined the potential reversibility of established uremic vascular calcification by treatment of uremic rats with BMP7. A control model of isogenic transplantation of a calcified aorta from uremic rats into healthy littermates examined whether normalization of the uremic environment reversed vascular calcification. Uremia and vascular calcification were induced in rats by 5/6 nephrectomy, high phosphate diet and alfacalcidol treatment. After 14 weeks severe vascular calcification was present and rats were allocated to BMP7, vehicle or aorta transplantation. BMP7 treatment caused a significant decrease of plasma phosphate to 1.56 ± 0.17 mmol/L vs 2.06 ± 0.34 mmol/L in the vehicle group even in the setting of uremia and high phosphate diet. Uremia and alfacalcidol resulted in an increase in aortic expression of genes related to fibrosis, osteogenic transformation and extracellular matrix calcification, and the BMP7 treatment resulted in a decrease in the expression of profibrotic genes. The total Ca-content of the aorta was however unchanged both in the abdominal aorta: 1.9 ± 0.6 μg/mg tissue in the vehicle group vs 2.2 ± 0.6 μg/mg tissue in the BMP7 group and in the thoracic aorta: 71 ± 27 μg/mg tissue in the vehicle group vs 54 ± 18 μg/mg tissue in the BMP7 group. Likewise, normalization of the uremic environment by aorta transplantation had no effect on the Ca-content of the calcified aorta: 16.3 ± 0.6 μg/mg tissue pre-transplantation vs 15.9 ± 2.3 μg/mg tissue post-transplantation. Aortic expression of genes directly linked to extracellular matrix calcification was not affected by BMP7 treatment, which hypothetically might explain persistent high Ca-content in established vascular calcification. The present results highlight the importance of preventing the development of vascular calcification in chronic kidney disease. Once established, vascular calcification persists even in the setting when hyperphosphatemia or the uremic milieu is abolished. PMID:29304096

Fibrovascular tissue in bilateral juxtafoveal telangiectasis.

PubMed

Park, D; Schatz, H; McDonald, H R; Johnson, R N

1996-09-01

To study the natural history and retinal findings associated with the intraretinal and subretinal fibrovascular tissues that develop in the late phases of bilateral juxtafoveal telangiectasis. The records of 10 patients (11 eyes) with bilateral juxtafoveal telangiectasis who developed these fibrovascular tissues were examined. Throughout the follow-up period (average 44 months), only 2 eyes (18%) lost 2 or more lines of vision; the final visual acuities were similar for the eyes both with and without fibrovascular tissues. Sixty-four percent of fibrovascular tissues showed little to no growth. Eyes with fibrovascular tissue commonly had retinal pigment epithelial hyperplasia (72%), draining retinal venules (82%), and retinal vascular distortion (64%). Fibrovascular tissues of bilateral juxtafoveal telangiectasis have little proliferative potential and minimal effects on visual acuity. Nevertheless, these fibrovascular tissues do remodel over time, leading to retinal vascular distortion. Given these benign findings, the role of laser photocoagulation treatment of these tissues is questionable.

Endoglin (CD105) expression in the development of haemorrhoids.

PubMed

Chung, Y-C; Hou, Y-C; Pan, A C-H

2004-02-01

Conventional pathogenesis of haemorrhoid emphasized the anchoring connective tissue system, whereas the vascular changes were ignored. The aim of this study was to clarify vascular changes of haemorrhoid disease. Forty-six samples of grade III and grade IV haemorrhoid tissue were selected for an in vitro study. We assessed the expressions in endoglin (CD105), an accessory protein in transforming growth factor-beta receptor complex, in CD34 and in vascular endothelial growth factor by using an immunohistochemical method. Microvascular density was calculated to correlate the expression of endoglin. Microvascular density was higher in haemorrhoid tissue than in normal anal and lower rectal tissues. CD34 was demonstrated in whole vessels in the haemorrhoids. However, endoglin, a proliferative marker of neovascularization, was present in only 25 of 46 (54%) haemorrhoidal vessels, and its immunoactivity was prominent in venules larger than 100 micro m. Thrombosis formation and stromal vascular endothelial growth factor was significantly associated with the presence of endoglin immunoactivity. The results of this study suggest that neovascularization is one important phenomenon of haemorrhoid disease, along with conventional venous dilatation and arteriovenous communication. In addition, thrombosis and stromal vascular endothelial growth factor might be important factors in promoting vascular proliferation.

Modelling the development and arrangement of the primary vascular structure in plants.

PubMed

Cartenì, Fabrizio; Giannino, Francesco; Schweingruber, Fritz Hans; Mazzoleni, Stefano

2014-09-01

The process of vascular development in plants results in the formation of a specific array of bundles that run throughout the plant in a characteristic spatial arrangement. Although much is known about the genes involved in the specification of procambium, phloem and xylem, the dynamic processes and interactions that define the development of the radial arrangement of such tissues remain elusive. This study presents a spatially explicit reaction-diffusion model defining a set of logical and functional rules to simulate the differentiation of procambium, phloem and xylem and their spatial patterns, starting from a homogeneous group of undifferentiated cells. Simulation results showed that the model is capable of reproducing most vascular patterns observed in plants, from primitive and simple structures made up of a single strand of vascular bundles (protostele), to more complex and evolved structures, with separated vascular bundles arranged in an ordered pattern within the plant section (e.g. eustele). The results presented demonstrate, as a proof of concept, that a common genetic-molecular machinery can be the basis of different spatial patterns of plant vascular development. Moreover, the model has the potential to become a useful tool to test different hypotheses of genetic and molecular interactions involved in the specification of vascular tissues.

Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues.

PubMed

Shimizu, Tatsuya

2014-01-01

In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.

[Research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering].

PubMed

Zhang, Haifeng; Han, Dong

2014-09-01

To review the application and research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering. The original articles about in vivo bioreactor that can enhance vascularization of tissue engineered bone were extensively reviewed and analyzed. The in vivo bioreactor can be created by periosteum, muscle, muscularis membrane, and fascia flap as well as biomaterials. Using in vivo bioreactor can effectively promote the establishment of a microcirculation in the tissue engineered bones, especially for large bone defects. However, main correlative researches, currently, are focused on animal experiments, more clinical trials will be carried out in the future. With the rapid development of related technologies of bone tissue engineering, the use of in vivo bioreactor will to a large extent solve the bottleneck limitations and has the potential values for clinical application.

Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

PubMed

Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

2015-05-01

During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue ingrowth and remodeling processes of the bone substitute. Extrinsic vessels contribute to faster vascularization and finally anastomose with intrinsic vasculature, allowing microvascular transplantation of the bone substitute after a shorter prevascularization time than using the intrinsic method only. It can be reasonably assumed that the usage of perforated chambers can significantly reduce the time until transplantation of bone constructs. Finally, this study paves the way for further preclinical testing for proof of the concept as a basis for early clinical applicability.

Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

PubMed Central

Yang, Hong; Zhao, Guang-Yue; Zhang, Geng; Lu, Zhi-Hong; Huang, Yan-Hong; Ma, Xiang-Dong; Liu, Hai-Xia; Liang, Sheng-Ru; Yang, Fang; Chen, Bi-Liang

2013-01-01

Objective To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. Methods In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. Results Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. Conclusion We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research. PMID:24278415

The Arteriovenous (AV) Loop in a Small Animal Model to Study Angiogenesis and Vascularized Tissue Engineering.

PubMed

Weigand, Annika; Beier, Justus P; Arkudas, Andreas; Al-Abboodi, Majida; Polykandriotis, Elias; Horch, Raymund E; Boos, Anja M

2016-11-02

A functional blood vessel network is a prerequisite for the survival and growth of almost all tissues and organs in the human body. Moreover, in pathological situations such as cancer, vascularization plays a leading role in disease progression. Consequently, there is a strong need for a standardized and well-characterized in vivo model in order to elucidate the mechanisms of neovascularization and develop different vascularization approaches for tissue engineering and regenerative medicine. We describe a microsurgical approach for a small animal model for induction of a vascular axis consisting of a vein and artery that are anastomosed to an arteriovenous (AV) loop. The AV loop is transferred to an enclosed implantation chamber to create an isolated microenvironment in vivo, which is connected to the living organism only by means of the vascular axis. Using 3D imaging (MRI, micro-CT) and immunohistology, the growing vasculature can be visualized over time. By implanting different cells, growth factors and matrices, their function in blood vessel network formation can be analyzed without any disturbing influences from the surroundings in a well controllable environment. In addition to angiogenesis and antiangiogenesis studies, the AV loop model is also perfectly suited for engineering vascularized tissues. After a certain prevascularization time, the generated tissues can be transplanted into the defect site and microsurgically connected to the local vessels, thereby ensuring immediate blood supply and integration of the engineered tissue. By varying the matrices, cells, growth factors and chamber architecture, it is possible to generate various tissues, which can then be tailored to the individual patient's needs.

Vascular pattern formation in plants.

PubMed

Scarpella, Enrico; Helariutta, Ykä

2010-01-01

Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns. Copyright 2010 Elsevier Inc. All rights reserved.

Impacts of Maternal Nutrition on Vascularity of Nutrient Transferring Tissues during Gestation and Lactation

PubMed Central

Vonnahme, Kimberly A.; Lemley, Caleb O.; Caton, Joel S.; Meyer, Allison M.

2015-01-01

As the demand for food increases with exponential growth in the world population, it is imperative that we understand how to make livestock production as efficient as possible in the face of decreasing available natural resources. Moreover, it is important that livestock are able to meet their metabolic demands and supply adequate nutrition to developing offspring both during pregnancy and lactation. Specific nutrient supplementation programs that are designed to offset deficiencies, enhance efficiency, and improve nutrient supply during pregnancy can alter tissue vascular responses, fetal growth, and postnatal offspring outcomes. This review outlines how vascularity in nutrient transferring tissues, namely the maternal gastrointestinal tract, the utero-placental tissue, and the mammary gland, respond to differing nutritional planes and other specific nutrient supplementation regimes. PMID:25984740

Tissue Bioeffects during Ultrasound-mediated Drug Delivery

NASA Astrophysics Data System (ADS)

Sutton, Jonathan

Ultrasound has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles, or ultrasound contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi, or direct drugs to optimal locations for delivery. These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery. This dissertation addresses a fundamental hypothesis in biomedical ultrasound: ultrasound-mediated drug delivery is capable of increasing the penetration of drugs across different physiologic barriers within the cardiovascular system, such as the vascular endothelium, blood clots, and smooth muscle cells.

Vascular Cambium Development

PubMed Central

Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

2015-01-01

Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.

PubMed

Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M; Jiang, Tao; Wirtel, Anthony J; Deng, Meng; Lv, Qing; Nair, Lakshmi S; Doty, Steven B; Laurencin, Cato T

2008-08-12

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: A combined gene therapy–cell transplantation approach

PubMed Central

Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M.; Jiang, Tao; Wirtel, Anthony J.; Deng, Meng; Lv, Qing; Nair, Lakshmi S.; Doty, Steven B.; Laurencin, Cato T.

2008-01-01

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials. PMID:18678895

A prokineticin-driven epigenetic switch regulates human epicardial cell stemness and fate.

PubMed

Qureshi, Rehana; Kindo, Michel; Boulberdaa, Mounia; von Hunolstein, Jean-Jacques; Steenman, Marja; Nebigil, Canan G

2018-06-06

Epicardial adipose tissues (EAT) and vascular tissues may both belong to the mesoepithelial lineage that develops from epicardium-derived progenitor cells (EPDCs) in developing and injured hearts. Very little is known of the molecular mechanisms of EPDC contribution in EAT development and neovascularization in adult heart, which the topic remains a subject of intense therapeutic interest and scientific debate. Here we studied the epigenetic control of stemness and anti-adipogenic and pro-vasculogenic fate of hEPDCs, through investigating an angiogenic hormone, prokineticin-2 (PK2) signaling via its receptor PKR1. We found that hEPDCs spontaneously undergoes epithelial-to-mesenchymal transformation (EMT), and are not predestined for the vascular lineages. However, PK2 via a histone demethylase KDM6A inhibits EMT, and induces asymmetric division, leading to self-renewal and formation of vascular and epithelial/endothelial precursors with angiogenic potential capable of differentiating into vascular smooth muscle and endothelial cells. PK2 upregulates and activates KDM6A to inhibit repressive histone H3K27me3 marks on promoters of vascular genes (Flk-1 and SM22α) involved in vascular lineage commitment and maturation. In PK2-mediated anti-adipogenic signaling, KDM6A stabilizes and increases cytoplasmic β-catenin levels to repress PPARγ expression and activity. Our findings offer additional molecular targets to manipulate hEPDCs-involved tissue repair/regeneration in cardiometabolic and ischemic heart diseases. This article is protected by copyright. All rights reserved. © 2018 AlphaMed Press.

Regulation of programmed cell death or apoptosis in atherosclerosis.

PubMed

Geng, Y J

1997-01-01

Intimal thickening caused by accumulation of cells, lipids, and connective tissue characterizes atherosclerosis, an arterial disease that leads to cardiac and cerebral infarction. Apoptosis, or genetically programmed cell death, is important for the development and morphogenesis of organs and tissues. As in other tissues, cells of cardiovascular tissues can undergo apoptosis. Increased apoptosis has been found in both human and animal atherosclerotic lesions, mediating tissue turnover and lesion development. In addition to vascular cells, many activated immune cells, mainly macrophages and T cells, are present in atherosclerotic lesions, where these cells produce biologically active substances such as the proinflammatory cytokines tumor necrosis factor, interleukin-1 (IL-1), and interferon-gamma. Simultaneous exposure to these cytokines may trigger apoptosis of vascular smooth muscle cells. The products of death-regulating genes including Fas/Fas ligand, members of IL-1 beta cysteinyl protease (caspase) family, the tumor suppressive gene p53, and the protooncogene c-myc have been found in vascular cells and may participate in the regulation of vascular apoptosis during the development of atherosclerosis. Abnormal occurrence of apoptosis may take place in atherosclerotic lesions, including attenuation or acceleration of the apoptotic death process. The former may cause an increase in the cellularity of the lesions, and the latter can reduce cellular components important for maintaining the integrity and stability of the plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of patients with atherosclerosis and its major complications, heart attack and stroke.

Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

PubMed

Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

2016-12-12

Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

3D bioprinting for vascularized tissue fabrication

PubMed Central

Richards, Dylan; Jia, Jia; Yost, Michael; Markwald, Roger; Mei, Ying

2016-01-01

3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication. PMID:27230253

Microcomputed tomography characterization of neovascularization in bone tissue engineering applications.

PubMed

Young, Simon; Kretlow, James D; Nguyen, Charles; Bashoura, Alex G; Baggett, L Scott; Jansen, John A; Wong, Mark; Mikos, Antonios G

2008-09-01

Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs.

Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine

PubMed Central

Upputuri, Paul Kumar; Sivasubramanian, Kathyayini; Mark, Chong Seow Khoon; Pramanik, Manojit

2015-01-01

Adequate vascularisation is key in determining the clinical outcome of stem cells and engineered tissue in regenerative medicine. Numerous imaging modalities have been developed and used for the visualization of vascularisation in tissue engineering. In this review, we briefly discuss the very recent advances aiming at high performance imaging of vasculature. We classify the vascular imaging modalities into three major groups: nonoptical methods (X-ray, magnetic resonance, ultrasound, and positron emission imaging), optical methods (optical coherence, fluorescence, multiphoton, and laser speckle imaging), and hybrid methods (photoacoustic imaging). We then summarize the strengths and challenges of these methods for preclinical and clinical applications. PMID:25821821

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

PubMed

Ren, Xiangkui; Feng, Yakai; Guo, Jintang; Wang, Haixia; Li, Qian; Yang, Jing; Hao, Xuefang; Lv, Juan; Ma, Nan; Li, Wenzhong

2015-08-07

Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis

PubMed Central

Manetti, Mirko; Guiducci, Serena; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

2010-01-01

Abstract Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem connective tissue disorder affecting the skin and various internal organs. Although the disease is characterized by a triad of widespread microangiopathy, fibrosis and autoimmunity, increasing evidence indicates that vascular damage is a primary event in the pathogenesis of SSc. The progressive vascular injury includes persistent endothelial cell activation/damage and apoptosis, intimal thickening, delamination, vessel narrowing and obliteration. These profound vascular changes lead to vascular tone dysfunction and reduced capillary blood flow, with consequent tissue ischemia and severe clinical manifestations, such as digital ulceration or amputation, pulmonary arterial hypertension and scleroderma renal crisis. The resulting tissue hypoxia induces complex cellular and molecular mechanisms in the attempt to recover endothelial cell function and tissue perfusion. Nevertheless, in SSc patients there is no evidence of significant angiogenesis and the disease evolves towards chronic tissue ischemia, with progressive and irreversible structural changes in multiple vascular beds culminating in the loss of capillaries. A severe imbalance between pro-angiogenic and angiostatic factors may also lead to impaired angiogenic response during SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers and functional defects of bone marrow-derived endothelial progenitor cells may contribute to the vascular pathogenesis of SSc. The purpose of this article is to review the contribution of recent studies to the understanding of the complex mechanisms of impaired vascular repair in SSc. Indeed, understanding the pathophysiology of SSc-associated vascular disease may be the key in dissecting the disease pathogenesis and developing novel therapies. Either angiogenic or vasculogenic mechanisms may potentially become in the future the target of therapeutic strategies to promote capillary regeneration in SSc. PMID:20132409

Vascular system modeling in parallel environment - distributed and shared memory approaches

PubMed Central

Jurczuk, Krzysztof; Kretowski, Marek; Bezy-Wendling, Johanne

2011-01-01

The paper presents two approaches in parallel modeling of vascular system development in internal organs. In the first approach, new parts of tissue are distributed among processors and each processor is responsible for perfusing its assigned parts of tissue to all vascular trees. Communication between processors is accomplished by passing messages and therefore this algorithm is perfectly suited for distributed memory architectures. The second approach is designed for shared memory machines. It parallelizes the perfusion process during which individual processing units perform calculations concerning different vascular trees. The experimental results, performed on a computing cluster and multi-core machines, show that both algorithms provide a significant speedup. PMID:21550891

New insights into insulin action and resistance in the vasculature

PubMed Central

Manrique, Camila; Lastra, Guido; Sowers, James R.

2014-01-01

Two-thirds of adults in the United States are overweight or obese, and another 26 million have type 2 diabetes. Decreased insulin sensitivity in cardiovascular tissue is an underlying abnormality in these individuals. Insulin metabolic signaling increases endothelial cell nitric oxide production. Impaired vascular insulin sensitivity is an early defect leading to impaired vascular relaxation. In overweight and obese persons, as well as in those with hypertension, systemic and vascular insulin resistance often occurs in conjunction with activation of the cardiovascular tissue renin–angiotensin–aldosterone system (RAAS). Activated angiotensin II type 1 receptor and mineralocorticoid receptor signaling promote the development of vascular insulin resistance and impaired endothelial nitric oxide–mediated relaxation. Research in this area has implicated excessive serine phosphorylation and proteasomal degradation of the docking protein insulin receptor substrate and enhanced signaling through hybrid insulin/insulin-like growth factor (IGF-1) receptor as important mechanisms underlying RAAS impediment of downstream vascular insulin metabolic signaling. This review will present recent evidence supporting the notion that RAAS signaling represents a potential pathway for the development of vascular insulin resistance and impaired endothelial-mediated vasodilation. PMID:24650277

Node-controlled allocation of mineral elements in Poaceae.

PubMed

Yamaji, Naoki; Ma, Jian Feng

2017-10-01

Mineral elements taken up by the roots will be delivered to different organs and tissues depending on their requirements. In Poaceae, this selective distribution is mainly mediated in the nodes, which have highly developed and fully organized vascular systems. Inter-vascular transfer of mineral elements from enlarged vascular bundles to diffuse vascular bundles is required for their preferential distribution to developing tissues and reproductive organs. A number of transporters involved in this inter-vascular transfer processes have been identified mainly in rice. They are localized at the different cell layers and form an efficient machinery within the node. Furthermore, some these transporters show rapid response to the environmental changes of mineral elements at the protein level. In addition to the node-based transporters, distinct nodal structures including enlarged xylem area, folded plasma membrane of xylem transfer cells and presence of an apoplastic barrier are also required for the efficient inter-vascular transfer. Manipulation of node-based transporters will provide a novel breeding target to improve nutrient use efficiency, productivity, nutritional value and safety in cereal crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using Digital Image Correlation to Characterize Local Strains on Vascular Tissue Specimens.

PubMed

Zhou, Boran; Ravindran, Suraj; Ferdous, Jahid; Kidane, Addis; Sutton, Michael A; Shazly, Tarek

2016-01-24

Characterization of the mechanical behavior of biological and engineered soft tissues is a central component of fundamental biomedical research and product development. Stress-strain relationships are typically obtained from mechanical testing data to enable comparative assessment among samples and in some cases identification of constitutive mechanical properties. However, errors may be introduced through the use of average strain measures, as significant heterogeneity in the strain field may result from geometrical non-uniformity of the sample and stress concentrations induced by mounting/gripping of soft tissues within the test system. When strain field heterogeneity is significant, accurate assessment of the sample mechanical response requires measurement of local strains. This study demonstrates a novel biomechanical testing protocol for calculating local surface strains using a mechanical testing device coupled with a high resolution camera and a digital image correlation technique. A series of sample surface images are acquired and then analyzed to quantify the local surface strain of a vascular tissue specimen subjected to ramped uniaxial loading. This approach can improve accuracy in experimental vascular biomechanics and has potential for broader use among other native soft tissues, engineered soft tissues, and soft hydrogel/polymeric materials. In the video, we demonstrate how to set up the system components and perform a complete experiment on native vascular tissue.

Vascular tissue engineering: the next generation.

PubMed

Cleary, Muriel A; Geiger, Erik; Grady, Conor; Best, Cameron; Naito, Yuji; Breuer, Christopher

2012-07-01

It is the ultimate goal of tissue engineering: an autologous tissue engineered vascular graft (TEVG) that is immunologically compatible, nonthrombogenic, and can grow and remodel. Currently, native vessels are the preferred vascular conduit for procedures such as coronary artery bypass (CABG) or peripheral bypass surgery. However, in many cases these are damaged, have already been harvested, or are simply unusable. The use of synthetic conduits is severely limited in smaller diameter vessels due to increased incidence of thrombosis, infection, and graft failure. Current research has therefore energetically pursued the development of a TEVG that can incorporate into a patient's circulatory system, mimic the vasoreactivity and biomechanics of the native vasculature, and maintain long-term patency. Copyright © 2012. Published by Elsevier Ltd.

Composite vascular scaffold combining electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves structure.

PubMed

Liu, Yuanyuan; Jiang, Chen; Li, Shuai; Hu, Qingxi

2016-08-01

While the field of tissue engineered vascular grafts has greatly advanced, many inadequacies still exist. Successfully developed scaffolds require mechanical and structural properties that match native vessels and optimal microenvironments that foster cell integration, adhesion and growth. We have developed a small diameter, three-layered composite vascular scaffold which consists of electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves by combining the electrospinning and dip-coating methods. Scaffold morphology and mechanics were assessed, quantified and compared to native vessels. Scaffolds were seeded with Human Umbilical Vein Endothelial Cells (HUVECs), cultured in vitro for 3 days and were evaluated for cell viability and morphology. The results showed that composite scaffolds had adjustable mechanical strength and favorable biocompatibility, which is important in the future clinical application of Tissue-engineered vascular grafts (TEVGs). Copyright © 2016 Elsevier Ltd. All rights reserved.

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

PubMed Central

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-01-01

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds. PMID:26758780

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

NASA Astrophysics Data System (ADS)

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-02-01

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair.

PubMed

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-02-12

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

PubMed

Elomaa, Laura; Yang, Yunzhi Peter

2017-10-01

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

Quickening: Translational design of resorbable synthetic vascular grafts.

PubMed

Stowell, Chelsea E T; Wang, Yadong

2018-08-01

Traditional tissue-engineered vascular grafts have yet to gain wide clinical use. The difficulty of scaling production of these cell- or biologic-based products has hindered commercialization. In situ tissue engineering bypasses such logistical challenges by using acellular resorbable scaffolds. Upon implant, the scaffolds become remodeled by host cells. This review describes the scientific and translational advantages of acellular, synthetic vascular grafts. It surveys in vivo results obtained with acellular synthetics over their fifty years of technological development. Finally, it discusses emerging principles, highlights strategic considerations for designers, and identifies questions needing additional research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

PubMed

Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

2014-02-01

In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

Implanted Cell-Dense Prevascularized Tissues Develop Functional Vasculature That Supports Reoxygenation After Thrombosis

PubMed Central

White, Sean M.; Pittman, Chelsea R.; Hingorani, Ryan; Arora, Rajan; Esipova, Tatiana V.; Vinogradov, Sergei A.; Hughes, Christopher C.W.; Choi, Bernard

2014-01-01

Achieving adequate vascularization within implanted engineered tissues is a significant obstacle to maintaining viability and functionality. In vitro prevascularization of engineered tissues has been explored as a potential solution to this challenge. The traditional paradigm of in vitro prevascularization is to implant an engineered tissue with a preformed vascular network that is perfused after anastomosis with the host circulation. We investigated the efficacy of this strategy by implanting cell-dense prevascularized tissues created via cell-mediated contraction and composed of collagen and a collagen-fibrin mixture into dorsal window chambers surgically prepared on immunocompromised mice. We found that host-implant anastomosis takes place in 2–6 days and that perfusion of vessels within the implants is subsequently restricted by thrombosis. However, by day 7, a functional vascular network composed of host and implant vessels developed. Prevascularization enhanced intra-implant pO2 significantly as early as 2 days postimplantation, reaching a maximum of 55 mmHg by day 8, which was significantly greater than the maximum within cellularized control tissues (18 mmHg). By day 14, collagen tissues supported ∼0.51×109 implanted and host-derived cells per mL. Our findings elucidate key features of in vitro prevascularization that can be used toward the design of larger and more functionally complex engineered tissues. PMID:24593148

Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage.

PubMed

Maes, Christa

2017-02-01

Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification. Copyright © 2016. Published by Elsevier Ltd.

Fabrication and preliminary study of a biomimetic tri-layer tubular graft based on fibers and fiber yarns for vascular tissue engineering.

PubMed

Wu, Tong; Zhang, Jialing; Wang, Yuanfei; Li, Dandan; Sun, Binbin; El-Hamshary, Hany; Yin, Meng; Mo, Xiumei

2018-01-01

Designing a biomimetic and functional tissue-engineered vascular graft has been urgently needed for repairing and regenerating defected vascular tissues. Utilizing a multi-layered vascular scaffold is commonly considered an effective way, because multi-layered scaffolds can easily simulate the structure and function of natural blood vessels. Herein, we developed a novel tri-layer tubular graft consisted of Poly(L-lactide-co-caprolactone)/collagen (PLCL/COL) fibers and Poly(lactide-co-glycolide)/silk fibroin (PLGA/SF) yarns via a three-step electrospinning method. The tri-layer vascular graft consisted of PLCL/COL aligned fibers in inner layer, PLGA/SF yarns in middle layer, and PLCL/COL random fibers in outer layer. Each layer possessed tensile mechanical strength and elongation, and the entire tubular structure provided tensile and compressive supports. Furthermore, the human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) proliferated well on the materials. Fluorescence staining images demonstrated that the axially aligned PLCL/COL fibers prearranged endothelium morphology in lumen and the circumferential oriented PLGA/SF yarns regulated SMCs organization along the single yarns. The outside PLCL/COL random fibers performed as the fixed layer to hold the entire tubular structure. The in vivo results showed that the tri-layer vascular graft supported cell infiltration, scaffold biodegradation and abundant collagen production after subcutaneous implantation for 10weeks, revealing the optimal biocompatibility and tissue regenerative capability of the tri-layer graft. Therefore, the specially designed tri-layer vascular graft will be beneficial to vascular reconstruction. Copyright © 2017. Published by Elsevier B.V.

Dual labeling of neural crest cells and blood vessels within chicken embryos using Chick(GFP) neural tube grafting and carbocyanine dye DiI injection.

PubMed

Delalande, Jean-Marie; Thapar, Nikhil; Burns, Alan J

2015-05-28

All developing organs need to be connected to both the nervous system (for sensory and motor control) as well as the vascular system (for gas exchange, fluid and nutrient supply). Consequently both the nervous and vascular systems develop alongside each other and share striking similarities in their branching architecture. Here we report embryonic manipulations that allow us to study the simultaneous development of neural crest-derived nervous tissue (in this case the enteric nervous system), and the vascular system. This is achieved by generating chicken chimeras via transplantation of discrete segments of the neural tube, and associated neural crest, combined with vascular DiI injection in the same embryo. Our method uses transgenic chick(GFP) embryos for intraspecies grafting, making the transplant technique more powerful than the classical quail-chick interspecies grafting protocol used with great effect since the 1970s. Chick(GFP)-chick intraspecies grafting facilitates imaging of transplanted cells and their projections in intact tissues, and eliminates any potential bias in cell development linked to species differences. This method takes full advantage of the ease of access of the avian embryo (compared with other vertebrate embryos) to study the co-development of the enteric nervous system and the vascular system.

Dual Labeling of Neural Crest Cells and Blood Vessels Within Chicken Embryos Using ChickGFP Neural Tube Grafting and Carbocyanine Dye DiI Injection

PubMed Central

Delalande, Jean-Marie; Thapar, Nikhil; Burns, Alan J.

2015-01-01

All developing organs need to be connected to both the nervous system (for sensory and motor control) as well as the vascular system (for gas exchange, fluid and nutrient supply). Consequently both the nervous and vascular systems develop alongside each other and share striking similarities in their branching architecture. Here we report embryonic manipulations that allow us to study the simultaneous development of neural crest-derived nervous tissue (in this case the enteric nervous system), and the vascular system. This is achieved by generating chicken chimeras via transplantation of discrete segments of the neural tube, and associated neural crest, combined with vascular DiI injection in the same embryo. Our method uses transgenic chickGFP embryos for intraspecies grafting, making the transplant technique more powerful than the classical quail-chick interspecies grafting protocol used with great effect since the 1970s. ChickGFP-chick intraspecies grafting facilitates imaging of transplanted cells and their projections in intact tissues, and eliminates any potential bias in cell development linked to species differences. This method takes full advantage of the ease of access of the avian embryo (compared with other vertebrate embryos) to study the co-development of the enteric nervous system and the vascular system. PMID:26065540

Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

PubMed Central

Young, Simon; Kretlow, James D.; Nguyen, Charles; Bashoura, Alex G.; Baggett, L. Scott; Jansen, John A.; Wong, Mark

2008-01-01

Abstract Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs. PMID:18657028

Human vascular renin-angiotensin system and its functional changes in relation to different sodium intakes.

PubMed

Boddi, M; Poggesi, L; Coppo, M; Zarone, N; Sacchi, S; Tania, C; Neri Serneri, G G

1998-03-01

A growing body of evidence supports the existence of a tissue-based renin-angiotensin system (RAS) in the vasculature, but the functional capacity of vascular RAS was not investigated in humans. In 28 normotensive healthy control subjects, the metabolism of angiotensins through vascular tissue was investigated in normal, low, and high sodium diets by the measurement of arterial-venous gradient of endogenous angiotensin (Ang) I and Ang II in two different vascular beds (forearm and leg), combined with the study of 125I-Ang I and 125I-Ang II kinetics. In normal sodium diet subjects, forearm vascular tissue extracted 36+/-6% of 125I-Ang I and 30+/-5% of 125I-Ang II and added 14.9+/-5.1 fmol x 100 mL(-1) x min(-1) of de novo formed Ang I and 6.2+/-2.8 fmol x 100 mL(-1) x min(-1) of Ang II to antecubital venous blood. Fractional conversion of 125I-Ang I through forearm vascular tissue was about 12%. Low sodium diet increased (P<.01) plasma renin activity, whereas de novo Ang I and Ang II formation by forearm vascular tissue became undetectable. Angiotensin degradation (33+/-7% for Ang I and 30+/-7% for Ang II) was unchanged, and vascular fractional conversion of 125I-Ang I decreased from 12% to 6% (P<.01). In high sodium diet subjects, plasma renin activity decreased, and de novo Ang I and Ang II formation by forearm vascular tissue increased to 22 and 14 fmol x 100 mL(-1) x min(-1), respectively (P<.01). Angiotensin degradation did not significantly change, whereas fractional conversion of 125I-Ang I increased from 12% to 20% (P<.01). Leg vascular tissue functional activities of RAS paralleled those of forearm vascular tissue both at baseline and during different sodium intake. These results provide consistent evidence for the existence of a functional tissue-based RAS in vascular tissue of humans. The opposite changes of plasma renin activity and vascular angiotensin formation indicate that vascular RAS is independent from but related to circulating RAS.

Multimodal imaging of vascular grafts using time-resolved fluorescence and ultrasound

NASA Astrophysics Data System (ADS)

Fatakdawala, Hussain; Griffiths, Leigh G.; Wong, Maelene L.; Humphrey, Sterling; Marcu, Laura

2015-02-01

The translation of engineered tissues into clinic requires robust monitoring of tissue development, both in vitro and in vivo. Traditional methods for the same are destructive, inefficient in time and cost and do not allow time-lapse measurements from the same sample or animal. This study reports on the ability of time-resolved fluorescence and ultrasound measurements for non-destructive characterization of explanted tissue engineered vascular grafts. Results show that TRFS and FLIm are able to assess alterations in luminal composition namely elastin, collagen and cellular (hyperplasia) content via changes in fluorescence lifetime values between normal and grafted tissue. These observations are complemented by structural changes observed in UBM pertaining to graft integration and intimal thickness over the grafted region. These results encourage the future application of a catheter-based technique that combines these imaging modalities for non-destructive characterization of vascular grafts in vivo.

Bioprinting of a functional vascularized mouse thyroid gland construct.

PubMed

Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

2017-08-18

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

Creating Perfused Functional Vascular Channels Using 3D Bio-Printing Technology

PubMed Central

Lee, Vivian K.; Kim, Diana Y.; Ngo, Haygan; Lee, Young; Seo, Lan; Yoo, Seung-Schik; Vincent, Peter A.; Dai, Guohao

2014-01-01

We developed a methodology using 3D bio-printing technology to create a functional in vitro vascular channel with perfused open lumen using only cells and biological matrices. The fabricated vasculature has a tight, confluent endothelium lining, presenting barrier function for both plasma protein and high-molecular weight dextran molecule. The fluidic vascular channel is capable of supporting the viability of tissue up to 5mm in distance at 5 million cells/mL density under the physiological flow condition. In static-cultured vascular channels, active angiogenic sprouting from the vessel surface was observed whereas physiological flow strongly suppressed this process. Gene expression analysis were reported in this study to show the potential of this vessel model in vascular biology research. The methods have great potential in vascularized tissue fabrication using 3D bio-printing technology as the vascular channel is simultaneously created while cells and matrix are printed around the channel in desired 3D patterns. It can also serve as a unique experimental tool for investigating fundamental mechanisms of vascular remodeling with extracellular matrix and maturation process under 3D flow condition. PMID:24965886

Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering.

PubMed

Wang, Martha O; Vorwald, Charlotte E; Dreher, Maureen L; Mott, Eric J; Cheng, Ming-Huei; Cinar, Ali; Mehdizadeh, Hamidreza; Somo, Sami; Dean, David; Brey, Eric M; Fisher, John P

2015-01-07

There is an unmet need for a consistent set of tools for the evaluation of 3D-printed constructs. A toolbox developed to design, characterize, and evaluate 3D-printed poly(propylene fumarate) scaffolds is proposed for vascularized engineered tissues. This toolbox combines modular design and non-destructive fabricated design evaluation, evaluates biocompatibility and mechanical properties, and models angiogenesis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

PubMed

van Kogelenberg, Sylvia; Yue, Zhilian; Dinoro, Jeremy N; Baker, Christopher S; Wallace, Gordon G

2018-05-01

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Smooth muscle architecture within cell-dense vascular tissues influences functional contractility.

PubMed

Win, Zaw; Vrla, Geoffrey D; Steucke, Kerianne E; Sevcik, Emily N; Hald, Eric S; Alford, Patrick W

2014-12-01

The role of vascular smooth muscle architecture in the function of healthy and dysfunctional vessels is poorly understood. We aimed at determining the relationship between vascular smooth muscle architecture and contractile output using engineered vascular tissues. We utilized microcontact printing and a microfluidic cell seeding technique to provide three different initial seeding conditions, with the aim of influencing the cellular architecture within the tissue. Cells seeded in each condition formed confluent and aligned tissues but within the tissues, the cellular architecture varied. Tissues with a more elongated cellular architecture had significantly elevated basal stress and produced more contractile stress in response to endothelin-1 stimulation. We also found a correlation between the contractile phenotype marker expression and the cellular architecture, contrary to our previous findings in non-confluent tissues. Taken with previous results, these data suggest that within cell-dense vascular tissues, smooth muscle contractility is strongly influenced by cell and tissue architectures.

Tie-dyed2 Encodes a Callose Synthase That Functions in Vein Development and Affects Symplastic Trafficking within the Phloem of Maize Leaves12[C][W][OA

PubMed Central

Slewinski, Thomas L.; Baker, R. Frank; Stubert, Adam; Braun, David M.

2012-01-01

The tie-dyed2 (tdy2) mutant of maize (Zea mays) displays variegated green and yellow leaves. Intriguingly, the yellow leaf tissues hyperaccumulate starch and sucrose, the soluble sugar transported long distance through the phloem of veins. To determine the molecular basis for Tdy2 function, we cloned the gene and found that Tdy2 encodes a callose synthase. RNA in situ hybridizations revealed that in developing leaves, Tdy2 was most highly expressed in the vascular tissue. Comparative expression analysis with the vascular marker maize PINFORMED1a-yellow fluorescent protein confirmed that Tdy2 was expressed in developing vein tissues. To ascertain whether the defect in tdy2 leaves affected the movement of sucrose into the phloem or its long-distance transport, we performed radiolabeled and fluorescent dye tracer assays. The results showed that tdy2 yellow leaf regions were defective in phloem export but competent in long-distance transport. Furthermore, transmission electron microscopy of tdy2 yellow leaf regions showed incomplete vascular differentiation and implicated a defect in cell-to-cell solute movement between phloem companion cells and sieve elements. The disruption of sucrose movement in the phloem in tdy2 mutants provides evidence that the Tdy2 callose synthase functions in vascular maturation and that the vascular defects result in impaired symplastic trafficking into the phloem translocation stream. PMID:22932757

The Decay of Stem Cell Nourishment at the Niche

PubMed Central

de Mora, Jaime Font

2013-01-01

Abstract One of the main features of human aging is the loss of adult stem cell homeostasis. Organs that are very dependent on adult stem cells show increased susceptibility to aging, particularly organs that present a vascular stem cell niche. Reduced regenerative capacity in tissues correlates with reduced stem cell function, which parallels a loss of microvascular density (rarefraction) and plasticity. Moreover, the age-related loss of microvascular plasticity and rarefaction has significance beyond metabolic support for tissues because stem cell niches are regulated co-ordinately with the vascular cells. In addition, microvascular rarefaction is related to increased inflammatory signals that may negatively regulate the stem cell population. Thus, the processes of microvascular rarefaction, adult stem cell dysfunction, and inflammation underlie the cycle of physiological decline that we call aging. Observations from new mouse models and humans are discussed here to support the vascular aging theory. We develop a novel theory to explain the complexity of aging in mammals and perhaps in other organisms. The connection between vascular endothelial tissue and organismal aging provides a potential evolutionary conserved mechanism that is an ideal target for the development of therapies to prevent or delay age-related processes in humans. PMID:23937078

Tissue-specific insulin signaling, metabolic syndrome and cardiovascular disease

PubMed Central

Rask-Madsen, Christian; Kahn, C. Ronald

2012-01-01

Summary Impaired insulin signaling is central to the development of the metabolic syndrome and can promote cardiovascular disease indirectly through development of abnormal glucose and lipid metabolism, hypertension and a proinflammatory state. However, insulin action directly on vascular endothelium, atherosclerotic plaque macrophages, and in the heart, kidney, and retina has now been described, and impaired insulin signaling in these locations can alter progression of cardiovascular disease in the metabolic syndrome and affect development of microvascular complications of diabetes. Recent advances in our understanding of the complex pathophysiology of insulin’s effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders. PMID:22895666

Mineralization/Anti-Mineralization Networks in the Skin and Vascular Connective Tissues

PubMed Central

Li, Qiaoli; Uitto, Jouni

2014-01-01

Ectopic mineralization has been linked to several common clinical conditions with considerable morbidity and mortality. The mineralization processes, both metastatic and dystrophic, affect the skin and vascular connective tissues. There are several contributing metabolic and environmental factors that make uncovering of the precise pathomechanisms of these acquired disorders exceedingly difficult. Several relatively rare heritable disorders share phenotypic manifestations similar to those in common conditions, and, consequently, they serve as genetically controlled model systems to study the details of the mineralization process in peripheral tissues. This overview will highlight diseases with mineral deposition in the skin and vascular connective tissues, as exemplified by familial tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, and arterial calcification due to CD73 deficiency. These diseases, and their corresponding mouse models, provide insight into the pathomechanisms of soft tissue mineralization and point to the existence of intricate mineralization/anti-mineralization networks in these tissues. This information is critical for understanding the pathomechanistic details of different mineralization disorders, and it has provided the perspective to develop pharmacological approaches to counteract the consequences of ectopic mineralization. PMID:23665350

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing.

PubMed

Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A; Lin, Charles P; Neville, Craig; Grottkau, Brian

2015-10-01

Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad applicability for evaluating vascularization in other engineered tissues as well.

Decoupling the effect of shear stress and stretch on tissue growth & remodeling in a vascular graft.

PubMed

van Haaften, Eline E; Wissing, Tamar B; Rutten, Marcel; Bulsink, Jurgen A; Gashi, Kujtim; van Kelle, Mathieu A J; Smits, Anthal; Bouten, Carlijn; Kurniawan, Nicholas A

2018-06-07

The success of cardiovascular tissue engineering strategies largely depends on the mechanical environment in which cells develop a neo-tissue via growth and remodeling processes. This mechanical environment is defined by the local scaffold architecture to which cells adhere, i.e., the micro-environment, and by external mechanical cues to which cells respond, i.e., hemodynamic loading. The hemodynamic environment of early-developing blood vessels consists of both shear stress (due to blood flow) and circumferential stretch (due to blood pressure). Experimental platforms that recapitulate this mechanical environment in a controlled and tunable manner are thus critical for investigating cardiovascular tissue engineering. In traditional perfusion bioreactors, however, shear stress and stretch are coupled, hampering a clear delineation of their effects on cell and tissue response. Here, we uniquely designed a bioreactor that independently combines these two types of mechanical cues in eight parallel vascular grafts. The system is computationally and experimentally validated, through finite element analysis and culture of tissue constructs respectively, to distinguish various levels of shear stress (up to 5 Pa) and cyclic stretch (up to 1.10). To illustrate the usefulness of the system, we investigated the relative contribution of cyclic stretch (1.05 at 0.5 Hz) and shear stress (1 Pa) to tissue development. Both types of hemodynamic loading contributed to cell alignment, but the contribution of shear stress overruled stretch-induced cell proliferation and matrix (i.e., collagen and glycosaminoglycan) production. At a macroscopic level, cyclic stretching led to the most linear stress-stretch response, which was not related to the presence of shear stress. In conclusion, we have developed a bioreactor that is particularly suited to further unravel the interplay between hemodynamics and in situ tissue engineering processes. Using the new system, the present work highlights the importance of hemodynamic loading to the study of developing vascular tissues.

Engineering vascularized soft tissue flaps in an animal model using human adipose–derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle

PubMed Central

Zhang, Qixu; Hubenak, Justin; Iyyanki, Tejaswi; Alred, Erik; Turza, Kristin C.; Davis, Greg; Chang, Edward I.; Branch-Brooks, Cynthia D.; Beahm, Elisabeth K.; Butler, Charles E.

2015-01-01

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold–stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model—hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber—provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects. PMID:26410787

Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle.

PubMed

Zhang, Qixu; Hubenak, Justin; Iyyanki, Tejaswi; Alred, Erik; Turza, Kristin C; Davis, Greg; Chang, Edward I; Branch-Brooks, Cynthia D; Beahm, Elisabeth K; Butler, Charles E

2015-12-01

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold-stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model-hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber-provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adipose-Derived Stromal Vascular Fraction Differentially Expands Breast Progenitors in Tissue Adjacent to Tumors Compared to Healthy Breast Tissue

PubMed Central

Chatterjee, Sumanta; Laliberte, Mike; Blelloch, Sarah; Ratanshi, Imran; Safneck, Janice; Buchel, Ed

2015-01-01

Background: Autologous fat grafts supplemented with adipose-derived stromal vascular fraction are used in reconstructive and cosmetic breast procedures. Stromal vascular fraction contains adipose-derived stem cells that are thought to encourage wound healing, tissue regeneration, and graft retention. Although use of stromal vascular fraction has provided exciting perspectives for aesthetic procedures, no studies have yet been conducted to determine whether its cells contribute to breast tissue regeneration. The authors examined the effect of these cells on the expansion of human breast epithelial progenitors. Methods: From patients undergoing reconstructive breast surgery following mastectomies, abdominal fat, matching tissue adjacent to breast tumors, and the contralateral non–tumor-containing breast tissue were obtained. Ex vivo co-cultures using breast epithelial cells and the stromal vascular fraction cells were used to study the expansion potential of breast progenitors. Breast reduction samples were collected as a source of healthy breast cells. Results: The authors observed that progenitors present in healthy breast tissue or contralateral non–tumor-containing breast tissue showed significant and robust expansion in the presence of stromal vascular fraction (5.2- and 4.8-fold, respectively). Whereas the healthy progenitors expanded up to 3-fold without the stromal vascular fraction cells, the expansion of tissue adjacent to breast tumor progenitors required the presence of stromal vascular fraction cells, leading to a 7-fold expansion, which was significantly higher than the expansion of healthy progenitors with stromal vascular fraction. Conclusions: The use of stromal vascular fraction might be more beneficial to reconstructive operations following mastectomies compared with cosmetic corrections of the healthy breast. Future studies are required to examine the potential risk factors associated with its use. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID:26090768

Spatial development of transport structures in apple (Malus × domestica Borkh.) fruit

PubMed Central

Herremans, Els; Verboven, Pieter; Hertog, Maarten L. A. T. M.; Cantre, Dennis; van Dael, Mattias; De Schryver, Thomas; Van Hoorebeke, Luc; Nicolaï, Bart M.

2015-01-01

The void network and vascular system are important pathways for the transport of gases, water and solutes in apple fruit (Malus × domestica Borkh). Here we used X-ray micro-tomography at various spatial resolutions to investigate the growth of these transport structures in 3D during fruit development of “Jonagold” apple. The size of the void space and porosity in the cortex tissue increased considerably. In the core tissue, the porosity was consistently lower, and seemed to decrease toward the end of the maturation period. The voids in the core were more narrow and fragmented than the voids in the cortex. Both the void network in the core and in the cortex changed significantly in terms of void morphology. An automated segmentation protocol underestimated the total vasculature length by 9–12% in comparison to manually processed images. Vascular networks increased in length from a total of 5 m at 9 weeks after full bloom, to more than 20 m corresponding to 5 cm of vascular tissue per cubic centimeter of apple tissue. A high degree of branching in both the void network and vascular system and a complex three-dimensional pattern was observed across the whole fruit. The 3D visualizations of the transport structures may be useful for numerical modeling of organ growth and transport processes in fruit. PMID:26388883

[Soft tissue defects treated with perforator flaps].

PubMed

Weum, Sven; de Weerd, Louis; Klein, Steven; Hage, J Joris

2008-01-31

Treatment of soft tissue defects caused by trauma, tumour surgery or pressure sores is a challenge to the reconstructive surgeon. Although contour and function may be restored by tissue transposition, traditional methods often cause significant donor site morbidity. This article describes how increased understanding of vascular anatomy has led to the development of new techniques. The article is based on textbooks of plastic surgery, selected articles and own clinical experience. Pedicled and free perforator flaps represent the latest development in surgical treatment of soft tissue defects. The use of perforator flaps can considerably reduce the disadvantages that are associated with other surgical methods. The use of perforator flaps demands microsurgical skills, but has many advantages. Reliable vascular supply and a good aesthetical result can be combined with minimal donor site morbidity. In many cases this technique may even give sensibility to the reconstructed area.

Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

PubMed

Vinatier, C; Guicheux, J

2016-06-01

Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Stem Cells and Scaffolds for Vascularizing Engineered Tissue Constructs

NASA Astrophysics Data System (ADS)

Luong, E.; Gerecht, S.

The clinical impact of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties from the molecular level up to organized tissue. Induction and creation of functional vascular networks has been one of the main goals of tissue engineering either in vitro, for the transplantation of prevascularized constructs, or in vivo, for cellular organization within the implantation site. In most cases, tissue engineering attempts to recapitulate certain aspects of normal development in order to stimulate cell differentiation and functional tissue assembly. The induction of tissue growth generally involves the use of biodegradable and bioactive materials designed, ideally, to provide a mechanical, physical, and biochemical template for tissue regeneration. Human embryonic stem cells (hESCs), derived from the inner cell mass of a developing blastocyst, are capable of differentiating into all cell types of the body. Specifically, hESCs have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. Human ESC-derived endothelial progenitor cells (EPCs) and endothelial cells have substantial potential for microvessel formation, in vitro and in vivo. Human adult EPCs are being isolated to understand the fundamental biology of how these cells are regulated as a population and to explore whether these cells can be differentiated and reimplanted as a cellular therapy in order to arrest or even reverse damaged vasculature. This chapter focuses on advances made toward the generation and engineering of functional vascular tissue, focusing on both the scaffolds - the synthetic and biopolymer materials - and the cell sources - hESCs and hEPCs.

Connective Tissue Growth Factor Is Involved in Structural Retinal Vascular Changes in Long-Term Experimental Diabetes

PubMed Central

Van Geest, Rob J.; Leeuwis, Jan Willem; Dendooven, Amélie; Pfister, Frederick; Bosch, Klazien; Hoeben, Kees A.; Vogels, Ilse M.C.; Van der Giezen, Dionne M.; Dietrich, Nadine; Hammes, Hans-Peter; Goldschmeding, Roel; Klaassen, Ingeborg; Van Noorden, Cornelis J.F.

2014-01-01

Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family member CCN2 or connective tissue growth factor (CTGF), a potent inducer of the expression of BL components, is upregulated early in diabetes. Diabetic mice lacking one functional CTGF allele (CTGF+/−) do not show this BL thickening. As early events in DR may be interrelated, we hypothesized that CTGF plays a role in the pathological changes of retinal capillaries other than BL thickening. We studied the effects of long-term (6-8 months) streptozotocin-induced diabetes on retinal capillary BL thickness, numbers of pericytes and the development of acellular capillaries in wild type and CTGF+/− mice. Our results show that an absence of BL thickening of retinal capillaries in long-term diabetic CTGF+/− mice is associated with reduced pericyte dropout and reduced formation of acellular capillaries. We conclude that CTGF is involved in structural retinal vascular changes in diabetic rodents. Inhibition of CTGF in the eye may therefore be protective against the development of DR. PMID:24217924

Tissue bioengineering and artificial organs.

PubMed

Llames, Sara; García, Eva; Otero Hernández, Jesús; Meana, Alvaro

2012-01-01

The scarcity of organs and tissues for transplant and the need of immunosuppressive drugs to avoid rejection constitute two reasons that justify organ and tissue production in the laboratory. Tissue engineering based tissues (TE) could allow to regenerate the whole organ from a fragment or even to produce several organs from an organ donor for grafting purposes. TE is based in: (1) the ex vivo expansion of cells, (2) the seeding of these expanded cells in tridimensional structures that mimic physiological conditions and, (3) grafting the prototype. In order to graft big structures it is necessary that the organ or tissue produced "ex vivo" bears a vascular tree to ensure the nutrition of its deep layers. At present, no technology has been developed to provide this vascular tree to TE derived products. Thus, these tissues must be thin enough to acquire nutrients during the first days by diffusion from surrounding tissues. This fact constitutes nowadays the greatest limitation of technologies for organ development in the laboratory.In this chapter, all these problems and their possible solutions are commented. Also, the present status of TE techniques in the regeneration of different organ systems is reviewed.

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

PubMed Central

Wang, Bo; Patnaik, Sourav S.; Brazile, Bryn; Butler, J. Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2016-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications. PMID:27480586

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

PubMed

Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2015-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

Adipose Tissue Angiogenesis: Impact on Obesity and Type-2 Diabetes

PubMed Central

Corvera, Silvia; Gealekman, Olga

2013-01-01

The growth and function of tissues is critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in turn increases type-2 diabetes risk. In addition, genetic and developmental factors involved in vascular patterning may define the size and expandability of diverse adipose tissue depots, which are also associated with type-2 diabetes risk. Moreover, the adipose tissue vasculature appears to be the niche for pre-adipocyte precursors, and factors that affect angiogenesis may directly impact the generation of new adipocytes. Here we review recent advances on the basic mechanisms of angiogenesis, and on the role of angiogenesis in adipose tissue development and obesity. A substantial amount of data point to a deficit in adipose tissue angiogenesis as a contributing factor to insulin resistance and metabolic disease in obesity. These emerging findings support the concept of the adipose tissue vasculature as a source of new targets for metabolic disease therapies. PMID:23770388

Tissue engineering therapy for cardiovascular disease.

PubMed

Nugent, Helen M; Edelman, Elazer R

2003-05-30

The present treatments for the loss or failure of cardiovascular function include organ transplantation, surgical reconstruction, mechanical or synthetic devices, or the administration of metabolic products. Although routinely used, these treatments are not without constraints and complications. The emerging and interdisciplinary field of tissue engineering has evolved to provide solutions to tissue creation and repair. Tissue engineering applies the principles of engineering, material science, and biology toward the development of biological substitutes that restore, maintain, or improve tissue function. Progress has been made in engineering the various components of the cardiovascular system, including blood vessels, heart valves, and cardiac muscle. Many pivotal studies have been performed in recent years that may support the move toward the widespread application of tissue-engineered therapy for cardiovascular diseases. The studies discussed include endothelial cell seeding of vascular grafts, tissue-engineered vascular conduits, generation of heart valve leaflets, cardiomyoplasty, genetic manipulation, and in vitro conditions for optimizing tissue-engineered cardiovascular constructs.

Development and validation of a LC-MS method for quantitation of ergot alkaloids in lateral saphenous vein tissue

USDA-ARS?s Scientific Manuscript database

A liquid chromatography-mass spectrometry (LC/MS) method for simultaneous quantitation of seven ergot alkaloids (lysergic acid, ergonovine, ergovaline, ergocornine, ergotamine, ergocryptine and ergocrystine) in vascular tissue was developed and validated. Reverse-phase chromatography, coupled to an...

Harnessing Sphingosine-1-Phosphate Signaling and Nanotopographical Cues To Regulate Skeletal Muscle Maturation and Vascularization.

PubMed

Tsui, Jonathan H; Janebodin, Kajohnkiart; Ieronimakis, Nicholas; Yama, David M P; Yang, Hee Seok; Chavanachat, Rakchanok; Hays, Aislinn L; Lee, Haeshin; Reyes, Morayma; Kim, Deok-Ho

2017-12-26

Despite possessing substantial regenerative capacity, skeletal muscle can suffer from loss of function due to catastrophic traumatic injury or degenerative disease. In such cases, engineered tissue grafts hold the potential to restore function and improve patient quality of life. Requirements for successful integration of engineered tissue grafts with the host musculature include cell alignment that mimics host tissue architecture and directional functionality, as well as vascularization to ensure tissue survival. Here, we have developed biomimetic nanopatterned poly(lactic-co-glycolic acid) substrates conjugated with sphingosine-1-phosphate (S1P), a potent angiogenic and myogenic factor, to enhance myoblast and endothelial maturation. Primary muscle cells cultured on these functionalized S1P nanopatterned substrates developed a highly aligned and elongated morphology and exhibited higher expression levels of myosin heavy chain, in addition to genes characteristic of mature skeletal muscle. We also found that S1P enhanced angiogenic potential in these cultures, as evidenced by elevated expression of endothelial-related genes. Computational analyses of live-cell videos showed a significantly improved functionality of tissues cultured on S1P-functionalized nanopatterns as indicated by greater myotube contraction displacements and velocities. In summary, our study demonstrates that biomimetic nanotopography and S1P can be combined to synergistically regulate the maturation and vascularization of engineered skeletal muscles.

[Characteristics of porcine thoracic arteries fixed with polyepoxy compound].

PubMed

Yu, Xi-Xun; Chen, Huai-Qing

2005-09-01

To investigate the characteristics of porcine thoracic arteries fixed with ethylene glycol diglycidyl ether (EX-810) and to provide the proper scaffold materials for tissue-engineered blood vessel. The porcine thoracic arteries were respectively treated with 40 ml/L EX-810 and 6.25 g/L glutaraldehyde, and then they were examined with naked-eye, light microscope and scanning electron microscope. The fixation index determination, the amino acid analysis and the biomechanics test were also performed. The antigenicity of vascular tissues can be diminished by EX-810 through getting rid of cell in the vascular tissues or reducing the level of free amino groups in the vascular tissues. The structural integrity of vascular tissues can be preserved after treatment with EX-810. It was also found that the EX-810-fixed porcine vascular tissues appeared more similar to the natural vascular tissues in color and mechanical properties, and were more pliable than the glutaraldehyde-fixed tissues. The EX-810-fixed porcine thoracic arteries with low cytotoxicity and low antigenicity showed favorable characteristic similar to those of natural vessel, and it should be a promising material for fabricating scaffold of tissue-engineered blood vessel.

[Vascular crisis after multiple tissue transplantation for thumb and other finger reconstruction by toe-to-hand transfer].

PubMed

Zhang, Jian; Huang, Jian; Pan, Jiadong; Zhou, Danya; Yin, Shanqing; Li, Junjie; Wang, Xin

2017-03-01

To explore the causes of vascular crisis after thumb and other finger reconstruction by toe-to-hand transfer and effective treatment methods so as to improve the survival rate of transplanted tissues. Between February 2012 and October 2015, 59 cases of thumb and other finger defects were repaired with different hallux nail flaps with the same vascular pedicle flap to reconstruct thumb and other fingers and repair skin defect. The donor site was repaired by a perforator flap. A total of 197 free tissues were involved. There were 46 males and 13 females with the average age of 30.6 years (range, 18-42 years). Vascular crisis occurred in 21 free tissues (10.7%) of 17 patients, including 9 arterial crisis (4.6%) of 8 cases, and 12 venous crisis (6.1%) of 10 cases. Conservative treatment was performed first; in 8 free tissues of 7 cases after failure of conservative treatment, anastomotic thrombosis was found in 5 free tissues of 4 cases, twisted vascular pedicle in 1 free tissue of 1 case, surrounding hematoma in 1 free tissue of 1 case, and anastomotic thrombosis associated with hematoma in 1 free tissue of 1 case, which underwent clearing hematoma, resecting embolization, regulating vascular tension, re-anastomosis or vascular transplantation. In 8 cases of arterial crisis, 5 free tissues of 5 cases survived after conservative treatment; partial necrosis occurred in 1 free tissue (1 case) of 4 free tissues (3 cases) undergoing surgical exploration. In 10 cases of venous crisis, 1 free tissue necrosis and 1 free tissue partial necrosis occurred in 8 free tissues (6 cases) undergoing conservative treatment; partial necrosis occurred in 1 free tissue of 4 free tissues (4 cases) undergoing surgical exploration. Free flap and skin graft were performed on 2 free tissues of 4 cases having flap necrosis respectively. Vascular crisis is complex and harmful to survival of transplanted tissue in reconstruction of the thumb and other fingers. Immediate intervention is helpful to obtain a higher survival rate.

Stromal vascular cells and adipogenesis: Cells within adipose depots regulate adipogenesis

USDA-ARS?s Scientific Manuscript database

A collection of investigations indicate the importance of adipose tissue stromal/stem cells to vasculogenesis and angiogenesis during adipogenesis. Early in development the stromal-vascular (S-V) elements control and dictate the extent of adipogenesis in a depot dependent manner. For instance, the...

Heparin Stimulates Elastogenesis: Application to Silk-Based Vascular Grafts

PubMed Central

Baughman, Cassandra; Kaplan, David L.; Castellot, John J.

2013-01-01

With over 500,000 coronary artery bypass grafts (CABG) performed annually in the United States alone, there is a significant clinical need for a small diameter tissue engineered vascular graft. A principle goal in tissue engineering is to develop materials and growth conditions that encourage appropriate re-cellularization and extracellular matrix formation in vivo. A particular challenge in vascular tissue engineering results from the inability of adult cells to produce elastin, as its expression is developmentally limited. We investigated factors to stimulate elastogenesis in vitro, and found that heparin treatment of adult human vascular smooth muscle cells promoted the formation of elastic fibers. This effect was heparin-specific, and dependent on cell density and growth state. We then applied this information to a silk-based construct, and found that immobilized heparin showed essentially identical biological effects to that of soluble heparin. These findings indicate that heparinized vascular grafts may promote elastin formation and regulate restenosis, in addition to heparin’s well-established antithrombotic properties. Given the increase in elastin mRNA level and the increase in extracellular elastin present, our data suggests that there may be multiple levels of elastin regulation that are mediated by heparin treatment. PMID:21600981

Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 Regulates Xylem Development and Growth by a Conserved Mechanism That Modulates Hormone Signaling1[W][OPEN

PubMed Central

Grienenberger, Etienne; Douglas, Carl J.

2014-01-01

Despite a strict conservation of the vascular tissues in vascular plants (tracheophytes), our understanding of the genetic basis underlying the differentiation of secondary cell wall-containing cells in the xylem of tracheophytes is still far from complete. Using coexpression analysis and phylogenetic conservation across sequenced tracheophyte genomes, we identified a number of Arabidopsis (Arabidopsis thaliana) genes of unknown function whose expression is correlated with secondary cell wall deposition. Among these, the Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 (VUP1) gene encodes a predicted protein of 24 kD with no annotated functional domains but containing domains that are highly conserved in tracheophytes. Here, we show that the VUP1 expression pattern, determined by promoter-β-glucuronidase reporter gene expression, is associated with vascular tissues, while vup1 loss-of-function mutants exhibit collapsed morphology of xylem vessel cells. Constitutive overexpression of VUP1 caused dramatic and pleiotropic developmental defects, including severe dwarfism, dark green leaves, reduced apical dominance, and altered photomorphogenesis, resembling brassinosteroid-deficient mutants. Constitutive overexpression of VUP homologs from multiple tracheophyte species induced similar defects. Whole-genome transcriptome analysis revealed that overexpression of VUP1 represses the expression of many brassinosteroid- and auxin-responsive genes. Additionally, deletion constructs and site-directed mutagenesis were used to identify critical domains and amino acids required for VUP1 function. Altogether, our data suggest a conserved role for VUP1 in regulating secondary wall formation during vascular development by tissue- or cell-specific modulation of hormone signaling pathways. PMID:24567189

Enzymatic regulation of functional vascular networks using gelatin hydrogels

PubMed Central

Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

2015-01-01

To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:25749296

Sucrose-Metabolizing Enzymes in Transport Tissues and Adjacent Sink Structures in Developing Citrus Fruit 1

PubMed Central

Lowell, Cadance A.; Tomlinson, Patricia T.; Koch, Karen E.

1989-01-01

Juice tissues of citrus lack phloem; therefore, photosynthates enroute to juice sacs exit the vascular system on the surface of each segment. Areas of extensive phloem unloading and transport (vascular bundles + segment epidermis) can thus be separated from those of assimilate storage (juice sacs) and adjacent tissues where both processes occur (peel). Sugar composition, dry weight accumulation, and activities of four sucrose-metabolizing enzymes (soluble and cell-wall-bound acid invertase, alkaline invertase, sucrose synthase, and sucrose phosphate synthase) were measured in these transport and sink tissues of grapefruit (Citrus paradisi Macf.) to determine more clearly whether a given enzyme appeared to be more directly associated with assimilate transport versus deposition or utilization. Results were compared at three developmental stages. Activity of sucrose (per gram fresh weight and per milligram protein) extracted from zones of extensive phloem unloading and transport was significantly greater than from adjacent sink tissues during the stages (II and III) when juice sacs grow most rapidly. In stage II fruit, activity of sucrose synthase also significantly surpassed that of all other sucrose-metabolizing enzymes in extracts from the transport tissues (vascular bundles + segment epidermis). In contrast, sucrose phosphate synthase and alkaline invertase at this stage of growth were the most active enzymes from adjacent, rapidly growing, phloem-free sink tissues (juice sacs). Activity of these two enzymes in extracts from juice sacs was significantly greater than that form the transport tissues (vascular bundles + segment epidermis). Soluble acid invertase was the most active enzyme in extracts from all tissues of very young fruit (stage I), including nonvascular regions, but nearly disappeared prior to the onset of juice sac sugar accumulation. The physiological function of high sucrose synthase activity in the transport tissues during rapid sucrose import remains to be determined. PMID:16666942

Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles

PubMed Central

Bible, Ellen; Qutachi, Omar; Chau, David Y.S.; Alexander, Morgan R.; Shakesheff, Kevin M.; Modo, Michel

2012-01-01

Replacing the tissue lost after a stroke potentially provides a new neural substrate to promote recovery. However, significant neurobiological and biotechnological challenges need to be overcome to make this possibility into a reality. Human neural stem cells (hNSCs) can differentiate into mature brain cells, but require a structural support that retains them within the cavity and affords the formation of a de novo tissue. Nevertheless, in our previous work, even after a week, this primitive tissue is void of a vasculature that could sustain its long-term viability. Therefore, tissue engineering strategies are required to develop a vasculature. Vascular endothelial growth factor (VEGF) is known to promote the proliferation and migration of endothelial cells during angio- and arteriogenesis. VEGF by itself here did not affect viability or differentiation of hNSCs, whereas growing cells on poly(D,L-lactic acid-co-glycolic acid) (PLGA) microparticles, with or without VEGF, doubled astrocytic and neuronal differentiation. Secretion of a burst and a sustained delivery of VEGF from the microparticles in vivo attracted endothelial cells from the host into this primate tissue and in parts established a neovasculature, whereas in other parts endothelial cells were merely interspersed with hNSCs. There was also evidence of a hypervascularization indicating that further work will be required to establish an adequate level of vascularization. It is therefore possible to develop a putative neovasculature within de novo tissue that is forming inside a tissue cavity caused by a stroke. PMID:22818980

Fluorescence and photodynamic effects of bacteriochlorin a observed in vivo in 'sandwich' observation chambers.

PubMed Central

van Leengoed, H. L.; Schuitmaker, J. J.; van der Veen, N.; Dubbelman, T. M.; Star, W. M.

1993-01-01

Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an effective photosensitiser in vitro and in vivo. BCA has a major absorption peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensitivity. The tissue localising and photodynamic properties of BCA were studied using isogeneic RMA mammary tumours, transplanted into subcutaneous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administration of 20 mg kg-1 BCA was assessed in blood vessels, tumour and normal tissue. Subsequently, the development of vascular- and tissue damage after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fifteen minutes post injection (p.i.), the fluorescence of BCA in the tumour reached a plateau value of 2.5 times the fluorescence in the normal tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed that of the normal tissue. Following photodynamic therapy (PDT), 24 h p.i., complete vascular stasis was observed 2 h post treatment in the tumour only, with subsequent recovery. The presence of viable tumour cells following PDT was assessed by histology and re-transplantation of treated tumour tissue from the chamber into the flank immediately or 7 days after treatment. In both cases tumour regrowth was observed. BCA-PDT (20 mg kg-1, 760 nm, 100 J cm-2) 1 h after BCA administration, an interval which gives the optimal differential between tumour and normal tissue, was sufficient to prevent tumour regrowth. However, this only occurred when re-transplantation was performed 7 days after PDT. During PDT, 1 h p.i., vascular damage in tumour and normal tissue was considerable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation damage was associated with vascular spasm and occlusion probably due to thrombi formation. Oedema was notable, especially following PDT with 600 J cm-2 at 24 h p.i. Images Figure 1 PMID:8494722

Pathophysiological consequences of VEGF-induced vascular permeability

NASA Astrophysics Data System (ADS)

Weis, Sara M.; Cheresh, David A.

2005-09-01

Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.

Vascular tissue engineering by computer-aided laser micromachining.

PubMed

Doraiswamy, Anand; Narayan, Roger J

2010-04-28

Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

PubMed

Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

2011-09-01

Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (< 6 mm) vessel replacements. While synthetic polymer alternatives to date have failed to meet the performance of autogenous conduits, tissue-engineered replacement vessels represent an ideal solution to this clinical problem. Ongoing progress requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

Interaction of Vascular Smooth Muscle Cells Under Low Shear Stress

NASA Technical Reports Server (NTRS)

Seidel, Charles L.

1998-01-01

The blood vessel wall consists of three cellular layers, an outer adventitial, a middle medial and an inner intimal layer. When the blood vessel forms in the embryo it begins as a tube composed of a single cell type called endothelial cells. Over time, other cells are recruited from the surrounding tissue to form additional layers on the outer surface of the endothelial tube. The cells that are recruited are called mesenchymal cells. Mesenchymal cells are responsible for the production of connective tissue that holds the blood vessel together and for developing into vascular smooth muscle cells that are responsible for regulating the diameter of the vessel (1) and therefore, blood flow. In a fully developed blood vessel, the endothelial cells make- up the majority of cells in the intimal layer while the mesenchymal cells make-up the majority of cells in the medial and adventitial layers. Within the medial layer of a mature vessel, cells are organized into multiple circular layers of alternating bands of connective tissue and cells. The cell layer is composed of a mixture of mesenchymal cells that have not developed into smooth muscle cells and fully developed smooth muscle cells (2). The assembly and organization of complex tissues is directed in part by a signaling system composed of proteins on the cell surface called adhesion molecules. Adhesion molecules enable cells to recognize each other as well as the composition of the connective tissue in which they reside (3). It was hypothesized that the different cell types that compose the vascular wall possess different adhesion molecules that enable them to recognize each other and through this recognition system, form the complex layered organization of the vascular wall. In other words, the layered organization is an intrinsic property of the cells. If this hypothesis is correct then the different cells that make up the vessel wall, when mixed together, should organize themselves into a layered structure resembling an intact blood vessel. Experiments described below were designed to test this hypothesis.

Diabetic retinopathy: retina-specific methods for maintenance of diabetic rodents and evaluation of vascular histopathology and molecular abnormalities

PubMed Central

Veenstra, Alexander; Liu, Haitao; Lee, Chieh Allen; Du, Yunpeng; Tang, Jie; Kern, Timothy S.

2015-01-01

Diabetic retinopathy is a major cause of visual impairment, which continues to increase in prevalence as more and more people develop diabetes. Despite the importance of vision, the retina is one of the smallest tissues in the body, and specialized techniques to study the retinopathy have been developed. This chapter will summarize several methods used to (i) induce diabetes, (ii) maintain the diabetic animals throughout the months required for the development of typical vascular histopathology, (iii) evaluate vascular histopathology of diabetic retinopathy, and (iv) quantitate abnormalities implicated in the development of the retinopathy. PMID:26331759

Effect of Prevascularization on In Vivo Vascularization of Poly(Propylene fumarate)/Fibrin Scaffolds

PubMed Central

Mishra, Ruchi; Roux, Brianna M.; Posukonis, Megan; Bodamer, Emily; Brey, Eric M.; Fisher, John P.; Dean, David

2016-01-01

The importance of vascularization in the field of bone tissue engineering has been established by previous studies. The present work proposes a novel poly(propylene fumarate) (PPF)/fibrin composite scaffold for the development of vascularized neobone tissue. The effect of prevascularization (i.e., in vitro pre-culture prior to implantation) with human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on in vivo vascularization of scaffolds was determined. Five conditions were studied: no pre-culture (NP), 1 week preculture (1P), 2 week pre-culture (2P), 3 week pre-culture (3P), and scaffolds without cells (control, C). Scaffolds were implanted subcutaneously in a severe combined immunodeficiency (SCID) mice model for 9 days. During in vitro studies, CD31 staining showed a significant increase in vascular network area over 3 weeks of culture. Vascular density was significantly higher in vivo when comparing NP to 3P groups. Immunohistochemical staining of human CD-31 expression indicated spreading of vascular networks with increasing pre-culture time. These vascular networks were perfused with mouse blood indicated by perfused lectin staining in human CD-31 positive vessels. Our results demonstrate that in vitro prevascularization supports in vivo vascularization in PPF/fibrin scaffolds. PMID:26606451

ECM-Based Materials in Cardiovascular Applications: Inherent Healing Potential and Augmentation of Native Regenerative Processes

PubMed Central

Piterina, Anna V.; Cloonan, Aidan J.; Meaney, Claire L.; Davis, Laura M.; Callanan, Anthony; Walsh, Michael T.; McGloughlin, Tim M.

2009-01-01

The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the progress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment. PMID:20057951

Periosteum tissue engineering in an orthotopic in vivo platform.

PubMed

Baldwin, J G; Wagner, F; Martine, L C; Holzapfel, B M; Theodoropoulos, C; Bas, O; Savi, F M; Werner, C; De-Juan-Pardo, E M; Hutmacher, D W

2017-03-01

The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated. In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs. Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Fabrication of viable and functional pre-vascularized modular bone tissues by coculturing MSCs and HUVECs on microcarriers in spinner flasks.

PubMed

Zhang, Songjie; Zhou, Min; Ye, Zhaoyang; Zhou, Yan; Tan, Wen-Song

2017-08-01

Slow vascularization often impedes the viability and function of engineered bone replacements. Prevascularization is a promising way to solve this problem. In this study, a new process was developed by integrating microcarrier culture and coculture to fabricate pre-vascularized bone microtissues with mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs). Initially, coculture medium and cell ratio between MSCs and HUVECs were optimized in tissue culture plates concerning cell proliferation, osteogenesis and angiogenesis. Subsequently, cells were seeded onto CultiSpher S microcarriers in spinner flasks and subjected to a two-stage (proliferative-osteogenic) culture process for four weeks. Both cells proliferated and functioned well in chosen medium and a 1 : 1 ratio between MSCs and HUVECs was chosen for better angiogenesis. After four weeks of culture in spinner flasks, the microtissues were formed with high cellularity, evenly distributed cells and tube formation ability. While coculture with HUVECs exerted an inhibitory effect on osteogenic differentiation of MSCs, with downregulated alkaline phosphatase activity, mineralization and gene expression of COLI, RUNX2 and OCN, this could be attenuated by employing a delayed seeding strategy of HUVECs against MSCs during the microtissue fabrication process. Collectively, this work established an effective method to fabricate pre-vascularized bone microtissues, which would lay a solid foundation for subsequent development of vascularized tissue grafts for bone regeneration. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of perivascular adipose tissue in vascular smooth muscle cell growth

PubMed Central

Miao, Chao-Yu; Li, Zhi-Yong

2012-01-01

Adipose tissue is the largest endocrine organ, producing various adipokines and many other substances. Almost all blood vessels are surrounded by perivascular adipose tissue (PVAT), which has not received research attention until recently. This review will discuss the paracrine actions of PVAT on the growth of underlying vascular smooth muscle cells (VSMCs). PVAT can release growth factors and inhibitors. Visfatin is the first identified growth factor derived from PVAT. Decreased adiponectin and increased tumour necrosis factor-α in PVAT play a pathological role for neointimal hyperplasia after endovascular injury. PVAT-derived angiotensin II, angiotensin 1–7, reactive oxygen species, complement component 3, NO and H2S have a paracrine action on VSMC contraction, endothelial or fibroblast function; however, their paracrine actions on VSMC growth remain to be directly verified. Factors such as monocyte chemoattractant protein-1, interleukin-6, interleukin-8, leptin, resistin, plasminogen activator inhibitor type-1, adrenomedullin, free fatty acids, glucocorticoids and sex hormones can be released from adipose tissue and can regulate VSMC growth. Most of them have been verified for their secretion by PVAT; however, their paracrine functions are unknown. Obesity, vascular injury, aging and infection may affect PVAT, causing adipocyte abnormality and inflammatory cell infiltration, inducing imbalance of PVAT-derived growth factors and inhibitors, leading to VSMC growth and finally resulting in development of proliferative vascular disease, including atherosclerosis, restenosis and hypertension. In the future, using cell-specific gene interventions and local treatments may provide definitive evidence for identification of key factor(s) involved in PVAT dysfunction-induced vascular disease and thus may help to develop new therapies. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21470202

Regeneration of Tissues and Organs Using Autologous Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthony Atala, M D

2012-10-11

The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bearmore » on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat conditions where other approaches have failed.« less

Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology.

PubMed

Augustin, Hellmut G; Koh, Gou Young

2017-08-25

Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed-specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Open Problems in Computational Vascular Biomechanics: Hemodynamics and Arterial Wall Mechanics

PubMed Central

Taylor, C.A.; Humphrey, J.D.

2009-01-01

The vasculature consists of a complex network of vessels ranging from large arteries to arterioles, capillaries, venules, and veins. This network is vital for the supply of oxygen and nutrients to tissues and the removal of carbon dioxide and waste products from tissues. Because of its primary role as a pressure-driven chemomechanical transport system, it should not be surprising that mechanics plays a vital role in the development and maintenance of the normal vasculature as well as in the progression and treatment of vascular disease. This review highlights some past successes of vascular biomechanics, but emphasizes the need for research that synthesizes complementary advances in molecular biology, biomechanics, medical imaging, computational methods, and computing power for purposes of increasing our understanding of vascular physiology and pathophysiology as well as improving the design of medical devices and clinical interventions, including surgical procedures. That is, computational mechanics has great promise to contribute to the continued improvement of vascular health. PMID:20161129

Medical adhesive-related skin injuries associated with vascular access.

PubMed

Hitchcock, Jan; Savine, Louise

2017-04-27

Establishing vascular access and preventing infection, both at insertion and during ongoing care is generally the top priority; the maintenance of optimal skin integrity is often a distant secondary consideration. Skin can react to different types of dressings or adhesives, or problems can arise relating to the securement of lines or the development of sensitivities to cleaning solutions. Clearly, these scenarios are not limited to the securement of vascular access devices; however, a patient with a long-term vascular access device may not have other options for vascular access, which makes this a very important and yet largely unrecognised area. A review of the limited literature that existed up to March 2015 showed it was typically concerned with skin tears connected with dressings and removal, and contact irritant dermatitis. The tissue viability team and vascular access team reviewed the current products associated with a typical vascular access dressing to ensure it was fit for purpose and where at all possible had good scientific literature for validation. The team worked proactively to recognise those patients at risk with the early identification of potential medical adhesive-related skin injuries (MARSI). To facilitate this an algorithm was developed that offers a step-by-step approach, clearly outlining what to do to prevent MARSI and its treatment should it develop. These reactions can result from other factors than the dressing alone, and an increase in these kinds of skin reaction in patients who are on chemotherapy regimens is being explored further. Through the implementation of an algorithm, education for both staff and patients and collaborative working between vascular access and tissue viability teams, a reduction in these phenomena has been seen despite an increasing number of at-risk patients.

In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

PubMed Central

Sekine, Hidekazu; Shimizu, Tatsuya; Sakaguchi, Katsuhisa; Dobashi, Izumi; Wada, Masanori; Yamato, Masayuki; Kobayashi, Eiji; Umezu, Mitsuo; Okano, Teruo

2013-01-01

In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications. PMID:23360990

A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering.

PubMed

Backman, Daniel E; LeSavage, Bauer L; Shah, Shivem B; Wong, Joyce Y

2017-06-01

In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm-PDMS substrates optimal for VSMC attachment. To allow long-term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm-PDMS surfaces were further modified with 3-aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single-layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single-layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First step toward near-infrared continuous glucose monitoring: in vivo evaluation of antibody coupled biomaterials

PubMed Central

Gellynck, Karolien; Kodeck, Valérie; Van De Walle, Elke; Kersemans, Ken; De Vos, Filip; Declercq, Heidi; Dubruel, Peter; Vlaminck, Lieven

2015-01-01

Continuous glucose monitoring (CGM) is crucial in diabetic care. Long-term CGM systems however require an accurate sensor as well as a suitable measuring environment. Since large intravenous sensors are not feasible, measuring inside the interstitial fluid is considered the best alternative. This option, unfortunately, has the drawback of a lag time with blood glucose values. A good strategy to circumvent this is to enhance tissue integration and enrich the peri-implant vasculature. Implants of different optically transparent biomaterials (poly(methyl-methacrylate) [PMMA] and poly(dimethylsiloxane) [PDMS]) – enabling glucose monitoring in the near-infrared (NIR) spectrum – were surface-treated and subsequently implanted in goats at various implantation sites for up to 3 months. The overall in vivo biocompatibility, tissue integration, and vascularization at close proximity of the surfaces of these materials were assessed. Histological screening showed similar tissue reactions independent of the implantation site. No significant inflammation reaction was observed. Tissue integration and vascularization correlated, to some extent, with the biomaterial composition. A modification strategy, in which a vascular endothelial-cadherin antibody was coupled to the biomaterials surface through a dopamine layer, showed significantly enhanced vascularization 3 months after subcutaneous implantation. Our results suggest that the developed strategy enables the creation of tissue interactive NIR transparent packaging materials, opening the possibility of continuous glucose monitoring. PMID:25304314

Exploring the potential of polyurethane-based soft foam as cell-free scaffold for soft tissue regeneration.

PubMed

Gerges, Irini; Tamplenizza, Margherita; Martello, Federico; Recordati, Camilla; Martelli, Cristina; Ottobrini, Luisa; Tamplenizza, Mariacaterina; Guelcher, Scott A; Tocchio, Alessandro; Lenardi, Cristina

2018-06-01

Reconstructive treatment after trauma and tumor resection would greatly benefit from an effective soft tissue regeneration. The use of cell-free scaffolds for adipose tissue regeneration in vivo is emerging as an attractive alternative to tissue-engineered constructs, since this approach avoids complications due to cell manipulation and lack of synchronous vascularization. In this study, we developed a biodegradable polyurethane-based scaffold for soft tissue regeneration, characterized by an exceptional combination between softness and resilience. Exploring the potential as a cell-free scaffold required profound understanding of the impact of its intrinsic physico-chemical properties on the biological performance in vivo. We investigated the effect of the scaffold's hydrophilic character, degradation kinetics, and internal morphology on (i) the local inflammatory response and activation of MGCs (foreign body response); (ii) its ability to promote rapid vascularisation, cell infiltration and migration through the scaffold over time; and (iii) the grade of maturation of the newly formed tissue into vascularized soft tissue in a murine model. The study revealed that soft tissue regeneration in vivo proceeded by gradual infiltration of undifferentiated mesenchymal cells though the periphery toward the center of the scaffold, where the rapid formation of a functional and well-formed vascular network supported cell viability overtime. Exploring the potential of polyurethane-based soft foam as cell-free scaffold for soft tissue regeneration. In this work, we address the unmet need for synthetic functional soft tissue substitutes that provide adequate biological and mechanical support to soft tissue. We developed a series of flexible cross-linked polyurethane copolymer scaffolds with remarkable fatigue-resistance and tunable physico-chemical properties for soft tissue regeneration in vivo. Accordingly, we could extend the potential of this class of biomaterials, which was so far confined for bone and osteochondral tissue regeneration, to other types of connective tissue. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

PubMed

Freeman, Fiona E; McNamara, Laoise M

2017-04-01

Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for bone tissue graft.

Effects of vascularization on cancer nanochemotherapy outcomes

NASA Astrophysics Data System (ADS)

Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

2016-08-01

Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules.

PubMed

Zhang, Wujie; Choi, Jung K; He, Xiaoming

2017-02-01

Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. This approach provides an alternative and promising method for constructing vascularized tissues.

Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

NASA Astrophysics Data System (ADS)

Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

2013-06-01

Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

PubMed

Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

2017-05-01

Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tissue engineering human small-caliber autologous vessels using a xenogenous decellularized connective tissue matrix approach: preclinical comparative biomechanical studies.

PubMed

Heine, Jörg; Schmiedl, Andreas; Cebotari, Serghei; Karck, Matthias; Mertsching, Heike; Haverich, Axel; Kallenbach, Klaus

2011-10-01

Suggesting that bioartificial vascular scaffolds cannot but tissue-engineered vessels can withstand biomechanical stress, we developed in vitro methods for preclinical biological material testings. The aim of the study was to evaluate the influence of revitalization of xenogenous scaffolds on biomechanical stability of tissue-engineered vessels. For measurement of radial distensibility, a salt-solution inflation method was used. The longitudinal tensile strength test (DIN 50145) was applied on bone-shaped specimen: tensile/tear strength (SigmaB/R), elongation at maximum yield stress/rupture (DeltaB/R), and modulus of elasticity were determined of native (NAs; n = 6), decellularized (DAs; n = 6), and decellularized carotid arteries reseeded with human vascular smooth muscle cells and human vascular endothelial cells (RAs; n = 7). Radial distensibility of DAs was significantly lower (113%) than for NAs (135%) (P < 0.001) or RAs (127%) (P = 0.018). At levels of 120 mm Hg and more, decellularized matrices burst (120, 160 [n = 2] and 200 mm Hg). Although RAs withstood levels up to 300 mm Hg, ANOVA revealed a significant difference from NA (P = 0.018). Compared with native vessels (NAs), SigmaB/R values were lower in DAs (44%; 57%) (P = 0.014 and P = 0.002, respectively) and were significantly higher in RAs (71%; 83%) (both P < 0.001). Similarly, DeltaB/R values were much higher in DAs compared with NAs (94%; 88%) (P < 0.001) and RAs (87%; 103%) (P < 0.001), but equivalent in NAs and RAs. Modulus of elasticity (2.6/1.1/3.7 to 16.6 N/mm(2)) of NAs, DAs, RAs was comparable (P = 0.088). Using newly developed in vitro methods for small-caliber vascular graft testing, this study proved that revitalization of decellularized connective tissue scaffolds led to vascular graft stability able to withstand biomechanical stress mimicking the human circulation. This tissue engineering approach provides a sufficiently stable autologized graft. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Ex vivo method to visualize and quantify vascular networks in native and tissue engineered skin.

PubMed

Egaña, José Tomás; Condurache, Alexandru; Lohmeyer, Jörn Andreas; Kremer, Mathias; Stöckelhuber, Beate M; Lavandero, Sergio; Machens, Hans-Günther

2009-03-01

Neovascularization plays a pivotal role in tissue engineering and tissue regeneration. However, reliable technologies to visualize and quantify blood vessel networks in target tissue areas are still pending. In this work, we introduce a new method which allows comparing vascularization levels in normal and tissue-engineered skin. Normal skin was isolated, and vascular dermal regeneration was analyzed based on tissue transillumination and computerized digital segmentation. For tissue-engineered skin, a bilateral full skin defect was created in a nude mouse model and then covered with a commercially available scaffold for dermal regeneration. After 3 weeks, the whole skin (including scaffold for dermal regeneration) was harvested, and vascularization levels were analyzed. The blood vessel network in the skin was better visualized by transillumination than by radio-angiographic studies, the gold standard for angiographies. After visualization, the whole vascular network was digitally segmented showing an excellent overlapping with the original pictures. Quantification over the digitally segmented picture was performed, and an index of vascularization area (VAI) and length (VLI) of the vessel network was obtained in target tissues. VAI/VLI ratio was calculated to obtain the vessel size index. We present a new technique which has several advantages compared to others, as animals do not require intravascular perfusions, total areas of interest can be quantitatively analyzed at once, and the same target tissue can be processed for further experimental analysis.

Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development.

PubMed

Lange, Clemens A K; Luhmann, Ulrich F O; Mowat, Freya M; Georgiadis, Anastasios; West, Emma L; Abrahams, Sabu; Sayed, Haroon; Powner, Michael B; Fruttiger, Marcus; Smith, Alexander J; Sowden, Jane C; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

2012-07-01

Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature.

The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes

PubMed Central

Poth, Jens M.; Fini, Mehdi A.; Olschewski, Andrea; El Kasmi, Karim C.; Stenmark, Kurt R.

2014-01-01

Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop “out-of-proportion” severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines (“second hit”) antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease. PMID:25416383

MicroRNAs in vascular tissue engineering and post-ischemic neovascularization☆

PubMed Central

Caputo, Massimo; Saif, Jaimy; Rajakaruna, Cha; Brooks, Marcus; Angelini, Gianni D.; Emanueli, Costanza

2015-01-01

Increasing numbers of paediatric patients with congenital heart defects are surviving to adulthood, albeit with continuing clinical needs. Hence, there is still scope for revolutionary new strategies to correct vascular anatomical defects. Adult patients are also surviving longer with the adverse consequences of ischemic vascular disease, especially after acute coronary syndromes brought on by plaque erosion and rupture. Vascular tissue engineering and therapeutic angiogenesis provide new hope for these patients. Both approaches have shown promise in laboratory studies, but have not yet been able to deliver clear evidence of clinical success. More research into biomaterials, molecular medicine and cell and molecular therapies is necessary. This review article focuses on the new opportunities offered by targeting microRNAs for the improved production and greater empowerment of vascular cells for use in vascular tissue engineering or for increasing blood perfusion of ischemic tissues by amplifying the resident microvascular network. PMID:25980937

Nestin in the epididymis is expressed in vascular wall cells and is regulated during postnatal development and in case of testosterone deficiency.

PubMed

Reckmann, Ansgar N; Tomczyk, Claudia U M; Davidoff, Michail S; Michurina, Tatyana V; Arnhold, Stefan; Müller, Dieter; Mietens, Andrea; Middendorff, Ralf

2018-01-01

Vascular smooth muscle cells (SMCs), distinguished by the expression of the neuronal stem cell marker nestin, may represent stem cell-like progenitor cells in various organs including the testis. We investigated epididymal tissues of adult nestin-GFP mice, rats after Leydig cell depletion via ethane dimethane sulfonate (EDS), rats and mice during postnatal development and human tissues. By use of Clarity, a histochemical method to illustrate a three-dimensional picture, we could demonstrate nestin-GFP positive cells within the vascular network. We localized nestin in the epididymis in proliferating vascular SMCs by colocalization with both smooth muscle actin and PCNA, and it was distinct from CD31-positive endothelial cells. The same nestin localization was found in the human epididymis. However, nestin was not found in SMCs of the epididymal duct. Nestin expression is high during postnatal development of mouse and rat and down-regulated towards adulthood when testosterone levels increase. Nestin increases dramatically in rats after Leydig cell ablation with EDS and subsequently low testosterone levels. Interestingly, during this period, the expression of androgen receptor in the epididymis is low and increases until nestin reaches normal levels of adulthood. Here we show that nestin, a common marker for neuronal stem cells, is also expressed in the vasculature of the epididymis. Our results give new insights into the yet underestimated role of proliferating nestin-expressing vascular SMCs during postnatal development and repair of the epididymis.

Induction of angiogenesis and neovascularization in adjacent tissue of plasma-collagen-coated silicone implants.

PubMed

Ring, Andrej; Langer, Stefan; Tilkorn, Daniel; Goertz, Ole; Henrich, Lena; Stricker, Ingo; Steinau, Hans-Ulrich; Steinstraesser, Lars; Hauser, Joerg

2010-09-28

Formation of encapsulating, avascular fibrous tissue is deemed to decrease implant's biocompatibility and versatility. We investigated whether plasma-mediated collagen coating possesses the ability to enhance neovascularization in the vicinity of silicone implants. Plasma-treated collagen-I-coated silicone samples were placed into the dorsal skinfold chambers of female balb/c mice (n = 10). Conventional silicone served as control (n = 10). Intravital microscopy was performed within implant's surrounding tissue on days 1, 5, and 10. Functional vessel density, intervascular distance, vessel diameter, microvascular permeability, red blood cell velocity, and leukocyte-endothelium interaction were determined. Enhanced angiogenesis in the tissue surrounding plasma-pretreated collagen-coated implants was noted. Significant increase of functional vessel density due to vascular new development was observed (t test, P < .05). Analyses of microvascular permeability and red blood cell velocity displayed stable perfusion of the vascular network neighboring the surface-modified implants. Intensified vascularity due to induced angiogenesis and neovascularization in the tissue surrounding plasma-collagen-coated samples were observed. These results indicate that plasma-mediated collagen coating might be a promising technology in order to improve the biocompatibility and versatility of silicone implants.

Induction of Angiogenesis and Neovascularization in Adjacent Tissue of Plasma-Collagen–Coated Silicone Implants

PubMed Central

Ring, Andrej; Langer, Stefan; Tilkorn, Daniel; Goertz, Ole; Henrich, Lena; Stricker, Ingo; Steinau, Hans-Ulrich; Steinstraesser, Lars; Hauser, Joerg

2010-01-01

Objective: Formation of encapsulating, avascular fibrous tissue is deemed to decrease implant's biocompatibility and versatility. We investigated whether plasma-mediated collagen coating possesses the ability to enhance neovascularization in the vicinity of silicone implants. Methods: Plasma-treated collagen-I–coated silicone samples were placed into the dorsal skinfold chambers of female balb/c mice (n = 10). Conventional silicone served as control (n = 10). Intravital microscopy was performed within implant's surrounding tissue on days 1, 5, and 10. Functional vessel density, intervascular distance, vessel diameter, microvascular permeability, red blood cell velocity, and leukocyte-endothelium interaction were determined. Results: Enhanced angiogenesis in the tissue surrounding plasma-pretreated collagen-coated implants was noted. Significant increase of functional vessel density due to vascular new development was observed (t test, P < .05). Analyses of microvascular permeability and red blood cell velocity displayed stable perfusion of the vascular network neighboring the surface-modified implants. Conclusion: Intensified vascularity due to induced angiogenesis and neovascularization in the tissue surrounding plasma-collagen–coated samples were observed. These results indicate that plasma-mediated collagen coating might be a promising technology in order to improve the biocompatibility and versatility of silicone implants. PMID:20936137

Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics.

PubMed

Jang, Jinah; Park, Ju Young; Gao, Ge; Cho, Dong-Woo

2018-02-01

Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next-generation therapeutics and diagnostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

A FSI computational framework for vascular physiopathology: A novel flow-tissue multiscale strategy.

PubMed

Bianchi, Daniele; Monaldo, Elisabetta; Gizzi, Alessio; Marino, Michele; Filippi, Simonetta; Vairo, Giuseppe

2017-09-01

A novel fluid-structure computational framework for vascular applications is herein presented. It is developed by combining the double multi-scale nature of vascular physiopathology in terms of both tissue properties and blood flow. Addressing arterial tissues, they are modelled via a nonlinear multiscale constitutive rationale, based only on parameters having a clear histological and biochemical meaning. Moreover, blood flow is described by coupling a three-dimensional fluid domain (undergoing physiological inflow conditions) with a zero-dimensional model, which allows to reproduce the influence of the downstream vasculature, furnishing a realistic description of the outflow proximal pressure. The fluid-structure interaction is managed through an explicit time-marching approach, able to accurately describe tissue nonlinearities within each computational step for the fluid problem. A case study associated to a patient-specific aortic abdominal aneurysmatic geometry is numerically investigated, highlighting advantages gained from the proposed multiscale strategy, as well as showing soundness and effectiveness of the established framework for assessing useful clinical quantities and risk indexes. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Effect of fibroin sponge coating on in vivo performance of knitted silk small diameter vascular grafts

PubMed Central

Fukayama, Toshiharu; Ozai, Yusuke; Shimokawadoko, Haruka; Aytemiz, Derya; Tanaka, Ryou; Machida, Noboru; Asakura, Tetsuo

2015-01-01

ABSTRACT Vascular grafts under 5 mm or less in diameter are not developed due to a problem caused by early thrombus formation, neointimal hyperplasia, etc. Bombyx mori silk fibroin (SF) which has biodegradability and tissue infiltration is focused as tube and coating material of vascular grafts. Coating is an important factor to maintain the strength of the anastomotic region of vascular grafts, and to prevent the blood leak from the vascular grafts after implantation. Therefore, in this research, we focused on the SF concentration of the coating solution, and tissue infiltration and remodeling were compared among each SF concentration. Silk poly (-ethylene) glycol diglycidyl ether (PGDE) coating with concentrations of 1.0%, 2.5%, 5.0%, and 7.5% SF were applied for the double-raschel knitted small-sized vessel with 1.5 mm diameter and 1cm in length. The grafts were implanted in the rat abdominal aorta and removed after 3 weeks or 3 months. Vascular grafts patency was monitored by ultrasound, and morphological evaluation was performed by histopathological examination. SF concentration had no significant effects on the patency rate. However, tissue infiltration was significantly higher in the sample of 2.5% SF in 3 weeks, and 1.0% and 2.5% SF in 3 months. Also, in comparison of length inside of the graft, stenosis were not found in 3 weeks, however, found with 5.0% and 7.5% in 3 months. From these results, it is clear that 2.5% SF coating is the most suitable concentration, based on the characteristics of less stenosis, early tissue infiltration, and less neointimal hyperplasia. PMID:26496652

Sites and Regulation of Polyamine Catabolism in the Tobacco Plant. Correlations with Cell Division/Expansion, Cell Cycle Progression, and Vascular Development1

PubMed Central

Paschalidis, Konstantinos A.; Roubelakis-Angelakis, Kalliopi A.

2005-01-01

We previously gave a picture of the homeostatic characteristics of polyamine (PA) biosynthesis and conjugation in tobacco (Nicotiana tabacum) plant organs during development. In this work, we present the sites and regulation of PA catabolism related to cell division/expansion, cell cycle progression, and vascular development in the tobacco plant. Diamine oxidase (DAO), PA oxidase (PAO), peroxidases (POXs), and putrescine N-methyltransferase expressions follow temporally and spatially discrete patterns in shoot apical cells, leaves (apical, peripheral, and central regions), acropetal and basipetal petiole regions, internodes, and young and old roots in developing plants. DAO and PAO produce hydrogen peroxide, a plant signal molecule and substrate for POXs. Gene expression and immunohistochemistry analyses reveal that amine oxidases in developing tobacco tissues precede and overlap with nascent nuclear DNA and also with POXs and lignification. In mature and old tissues, flow cytometry indicates that amine oxidase and POX activities, as well as pao gene and PAO protein levels, coincide with G2 nuclear phase and endoreduplication. In young versus the older roots, amine oxidases and POX expression decrease with parallel inhibition of G2 advance and endoreduplication, whereas putrescine N-methyltransferase dramatically increases. In both hypergeous and hypogeous tissues, DAO and PAO expression occurs in cells destined to undergo lignification, suggesting a different in situ localization. DNA synthesis early in development and the advance in cell cycle/endocycle are temporally and spatially related to PA catabolism and vascular development. PMID:16040649

Patterning vascular networks in vivo for tissue engineering applications.

PubMed

Chaturvedi, Ritika R; Stevens, Kelly R; Solorzano, Ricardo D; Schwartz, Robert E; Eyckmans, Jeroen; Baranski, Jan D; Stapleton, Sarah Chase; Bhatia, Sangeeta N; Chen, Christopher S

2015-05-01

The ultimate design of functionally therapeutic engineered tissues and organs will rely on our ability to engineer vasculature that can meet tissue-specific metabolic needs. We recently introduced an approach for patterning the formation of functional spatially organized vascular architectures within engineered tissues in vivo. Here, we now explore the design parameters of this approach and how they impact the vascularization of an engineered tissue construct after implantation. We used micropatterning techniques to organize endothelial cells (ECs) into geometrically defined "cords," which in turn acted as a template after implantation for the guided formation of patterned capillaries integrated with the host tissue. We demonstrated that the diameter of the cords before implantation impacts the location and density of the resultant capillary network. Inclusion of mural cells to the vascularization response appears primarily to impact the dynamics of vascularization. We established that clinically relevant endothelial sources such as induced pluripotent stem cell-derived ECs and human microvascular endothelial cells can drive vascularization within this system. Finally, we demonstrated the ability to control the juxtaposition of parenchyma with perfused vasculature by implanting cords containing a mixture of both a parenchymal cell type (hepatocytes) and ECs. These findings define important characteristics that will ultimately impact the design of vasculature structures that meet tissue-specific needs.

WNT5A-JNK regulation of vascular insulin resistance in human obesity.

PubMed

Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

2016-12-01

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

WNT5A-JNK regulation of vascular insulin resistance in human obesity

PubMed Central

Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

2017-01-01

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m2) and five metabolically normal non-obese (BMI 26±2 kg/m2) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. PMID:27688298

An examination of the genetic control of Douglas-fir vascular tissue phytochemicals: implications for black bear foraging.

Treesearch

Bruce A. Kimball; G.R. Johnson; Dale L. Nolte; Doreen L. Griffin

1999-01-01

Silvicultural practices can influence black bear (Ursus americanus) foraging preferences for Douglas-fir (Pseudotsuga menziesii) cambial-zone vascular tissues, but little is known about the role of genetics. To study the impact of genetic selection, vascular tissue samples were collected from Douglas-fir trees in six half-sib families from five...

FGF-dependent metabolic control of vascular development

PubMed Central

Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

FGF-dependent metabolic control of vascular development.

PubMed

Yu, Pengchun; Wilhelm, Kerstin; Dubrac, Alexandre; Tung, Joe K; Alves, Tiago C; Fang, Jennifer S; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G; Hirschi, Karen K; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-05-11

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context. Here we identify FGF receptor (FGFR) signalling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signalling inputs results in decreased glycolysis, leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/Fgfr3 double mutant mice, while HK2 overexpression partly rescues the defects caused by suppression of FGF signalling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development.

Engineering clinically relevant volumes of vascularized bone

PubMed Central

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-01-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. PMID:25877690

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos

USGS Publications Warehouse

Toomey, B.H.; Bello, S.; Hahn, M.E.; Cantrell, S.; Wright, P.; Tillitt, D.E.; Di Giulio, R.T.

2001-01-01

Fundulus heteroclitus embryos were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early development using nanoinjection or water bath exposure. TCDD caused developmental abnormalities that included hemorrhaging, loss of vascular integrity, edema, stunted development and death. The LC50 and LD50 of TCDD for Fundulus embryos were ???19.7??9.5 pg TCDD/??l (water bath) and 0.25??0.09 ng TCDD/g embryo (nanoinjection). To identify a possible cause for these developmental abnormalities we analyzed the effects of TCDD on apoptotic cell death and cytochrome P4501A (CYP1A) expression in the embryos. TCDD exposure increased apoptotic cell death in several tissues including brain, eye, gill, kidney, tail, intestine, heart, and vascular tissue. CYP1A expression was also increased in the TCDD-exposed embryos predominantly in liver, kidney, gill, heart, intestine, and in vascular tissues throughout the embryo. There was co-occurrence of TCDD-induced apoptosis and CYP1A expression in some, but not all, cell types. In addition the dose response relationships for apoptosis and mortality were similar, while CYP1A expression appeared more sensitive to TCDD induction. Copyright ?? 2001 Elsevier Science B.V.

Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

PubMed Central

Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

2016-01-01

We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

Vascular repair strategies in type 2 diabetes: novel insights

PubMed Central

Kuschnerus, Kira; Landmesser, Ulf

2015-01-01

Impaired functions of vascular cells are responsible for the majority of complications in patients with type 2 diabetes (T2D). Recently a better understanding of mechanisms contributing to development of vascular dysfunction and the role of systemic inflammatory activation and functional alterations of several secretory organs, of which adipose tissue has more recently been investigated, has been achieved. Notably, the progression of vascular disease within the context of T2D appears to be driven by a multitude of incremental signaling shifts. Hence, successful therapies need to target several mechanisms in parallel, and over a long time period. This review will summarize the latest molecular strategies and translational developments of cardiovascular therapy in patients with T2D. PMID:26543824

Multiparametric evaluation of hindlimb ischemia using time-series indocyanine green fluorescence imaging.

PubMed

Guang, Huizhi; Cai, Chuangjian; Zuo, Simin; Cai, Wenjuan; Zhang, Jiulou; Luo, Jianwen

2017-03-01

Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time-series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time-series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post-ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time-varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time-series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo-perfused tissues from well-perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis. The estimated perfusion rate and vascular perfusion density maps (left) and the time-varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel Mammary Fat Pad Transplantation Technique to Visualize the Vessel Generation of Vascular Endothelial Stem Cells.

PubMed

Yu, Qing Cissy; Song, Wenqian; Lai, Dengwen; Zeng, Yi Arial

2017-08-03

Endothelial cells (ECs) are the fundamental building blocks of the vascular architecture and mediate vascular growth and remodeling to ensure proper vessel development and homeostasis. However, studies on endothelial lineage hierarchy remain elusive due to the lack of tools to gain access as well as to directly evaluate their behavior in vivo. To address this shortcoming, a new tissue model to study angiogenesis using the mammary fat pad has been developed. The mammary gland develops mostly in the postnatal stages, including puberty and pregnancy, during which robust epithelium proliferation is accompanied by extensive vascular remodeling. Mammary fat pads provide space, matrix, and rich angiogenic stimuli from the growing mammary epithelium. Furthermore, mammary fat pads are located outside the peritoneal cavity, making them an easily accessible grafting site for assessing the angiogenic potential of exogenous cells. This work also describes an efficient tracing approach using fluorescent reporter mice to specifically label the targeted population of vascular endothelial stem cells (VESCs) in vivo. This lineage tracing method, coupled with subsequent tissue whole-mount microscopy, enable the direct visualization of targeted cells and their descendants, through which the proliferation capability can be quantified and the differentiation commitment can be fate-mapped. Using these methods, a population of bipotent protein C receptor (Procr) expressing VESCs has recently been identified in multiple vascular systems. Procr + VESCs, giving rise to both new ECs and pericytes, actively contribute to angiogenesis during development, homeostasis, and injury repair. Overall, this manuscript describes a new mammary fat pad transplantation and in vivo lineage tracing techniques that can be used to evaluate the stem cell properties of VESCs.

Dual ECM Biomimetic Scaffolds for Dental Pulp Regenerative Applications

PubMed Central

Huang, Chun-Chieh; Narayanan, Raghuvaran; Warshawsky, Noah; Ravindran, Sriram

2018-01-01

Dental pulp is a highly vascularized and innervated tissue that provides sensitivity and vitality to the tooth. Chronic caries results in an infected pulp tissue prone to necrosis. Existing clinical treatments replace the living pulp tissue with a non-responsive resin filling resulting in loss of tooth vitality. Tissue engineering approaches to dental pulp tissue regeneration have been investigated to preserve tooth vitality and function. However, a critical criterion is the choice of growth factors that may promote mesenchymal stem cell differentiation and more importantly, vascularization. But, the problems associated with growth factor dosage, delivery, safety, immunological and ectopic complications affect their translatory potential severely. The purpose of this study is to develop, characterize and evaluate a biomimetic native extracellular matrix (ECM) derived dual ECM scaffold that consists of a pulp-specific ECM to promote MSC attachment, proliferation and differentiation and an endothelial ECM to promote migration of host endothelial cells and eventual vascularization in vivo. Our results show that the dual ECM scaffolds possess similar properties as a pulp-ECM scaffold to promote MSC attachment and odontogenic differentiation in vitro. Additionally, when implanted subcutaneously in a tooth root slice model in vivo, the dual ECM scaffolds promoted robust odontogenic differentiation of both dental pulp and bone marrow derived MSCs and also extensive vascularization when compared to respective controls. These scaffolds are mass producible for clinical use and hence have the potential to replace root canal therapy as a treatment for chronic dental caries. PMID:29887803

Comprehensive mechanical characterization of PLA fabric combined with PCL to form a composite structure vascular graft.

PubMed

Li, Chaojing; Wang, Fujun; Douglas, Graeham; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-05-01

Vascular grafts made by tissue engineering processes are prone to buckling and twisting, which can impede blood flow and lead to collapse of the vessel. These vascular conduits may suffer not only from insufficient tensile strength, but also from vulnerabilities related to compression, torsion, and pulsatile pressurization. Aiming to develop a tissue engineering-inspired blood conduit, composite vascular graft (cVG) prototypes were created by combining a flexible polylactic acid (PLA) knitted fabric with a soft polycaprolactone (PCL) matrix. The graft is to be populated in-situ with cellular migration and proliferation into the device. Comprehensive characterizations probed the relationship between structure and mechanical properties of the different cVG prototypes. The composite grafts exhibited major improvements in mechanical characteristics compared to single-material devices, with particular improvement in compression and torsional resistance. A commercial expanded polytetrafluoroethylene (ePTFE) vascular graft was used as a control against the proposed composite vascular grafts. CVG devices showed high tensile strength, high bursting strength, and improved suture retention. Compression, elastic recovery, and compliance were similar to those for the ePTFE graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advanced life systems hardware development for future missions

NASA Technical Reports Server (NTRS)

1975-01-01

An examination of the pulse formation in an externalized vessel suggests that the vessel does not behave as a simple visco-elastic tube. Pressure-pulse waveform transducers are sensitive either to the pressure present at the vessel wall or to the volume of blood filling a region of tissue. Results of comparisons between intra-and extra-vascular pressure recordings suggest that changes in vasomotor tone and transducer-vessel pressures may be the greatest contributors to the divergence of extra-vascular waveforms from intra-vascular waveforms.

Generating favorable growth factor and protease release profiles to enable extracellular matrix accumulation within an in vitro tissue engineering environment.

PubMed

Zhang, Xiaoqing; Battiston, Kyle G; Labow, Rosalind S; Simmons, Craig A; Santerre, J Paul

2017-05-01

Tissue engineering (particularly for the case of load-bearing cardiovascular and connective tissues) requires the ability to promote the production and accumulation of extracellular matrix (ECM) components (e.g., collagen, glycosaminoglycan and elastin). Although different approaches have been attempted in order to enhance ECM accumulation in tissue engineered constructs, studies of underlying signalling mechanisms that influence ECM deposition and degradation during tissue remodelling and regeneration in multi-cellular culture systems have been limited. The current study investigated vascular smooth muscle cell (VSMC)-monocyte co-culture systems using different VSMC:monocyte ratios, within a degradable polyurethane scaffold, to assess their influence on ECM generation and degradation processes, and to elucidate relevant signalling molecules involved in this in vitro vascular tissue engineering system. It was found that a desired release profile of growth factors (e.g. insulin growth factor-1 (IGF-1)) and hydrolytic proteases (e.g. matrix-metalloproteinases 2, 9, 13 and 14 (MMP2, MMP9, MMP13 and MMP14)), could be achieved in co-culture systems, yielding an accumulation of ECM (specifically for 2:1 and 4:1 VSMC:monocyte culture systems). This study has significant implications for the tissue engineering field (including vascular tissue engineering), not only because it identified important cytokines and proteases that control ECM accumulation/degradation within synthetic tissue engineering scaffolds, but also because the established culture systems could be applied to improve the development of different types of tissue constructs. Sufficient extracellular matrix accumulation within cardiovascular and connective tissue engineered constructs is a prerequisite for their appropriate function in vivo. This study established co-culture systems with tissue specific cells (vascular smooth muscle cells (VSMCs)) and defined ratios of immune cells (monocytes) to investigate extracellular matrix (ECM) generation and degradation processes, revealing important mechanisms underlying ECM turnover during vascular tissue regeneration/remodelling. A specific growth factor (IGF-1), as well as hydrolytic proteases (e.g. MMP2, MMP9, MMP13 and MMP14), were identified as playing important roles in these processes. ECM accumulation was found to be dependent on achieving a desired release profile of these ECM-promoting and ECM-degrading factors within the multi-cellular microenvironment. The findings enhance our understanding of ECM deposition and degradation during in vitro tissue engineering and would be applicable to the repair or regeneration of a variety of tissues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Prefabricated microvascular autograft in tracheal reconstruction.

PubMed

Fayad, J; Kuriloff, D B

1994-10-01

Tracheal reconstruction continues to be a challenge in head and neck surgery. Numerous techniques, including the use of alloplasts, composite grafts, and staged laryngotracheal troughs, have met with limited success because of implant exposure, infection, persistent granulation tissue, and eventual restenosis. With recently introduced techniques for soft-tissue molding, bone induction with bone morphogenetic protein, and microvascular free tissue transfer, a rodent model was developed to create a well-vascularized tracheal autograft. In this model, a rigid tube having the same dimensions and flexibility as the native trachea was created by wrapping a cylindrical silicone tracheal mold with a layer of vascularized adductor thigh muscle pedicled on the femoral vessels in the groin. Tracheal rings were created by filing transverse troughs in the muscle bed with bone morphogenetic protein-primed demineralized bone matrix before wrapping around the silicone mold. Grafts harvested at 2 weeks demonstrated rigid skeletal support provided by heterotopic bone formation in the form of rings and a smooth inner lining produced by fibroplasia. Bone transformation was controlled and restricted to the muscle troughs, allowing intervening regions of soft tissue and thus producing a flexible neotrachia. With this model, a homologous, vascularized tracheal autograft capable of microvascular free tissue transfer was fabricated based on the femoral vessels. Prefabrication of composite grafts, through the use of soft-tissue molding, bone induction, and subsequent free tissue transfer, has an unlimited potential for use in head and neck reconstruction.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.

PubMed

Ball, Owen; Nguyen, Bao-Ngoc B; Placone, Jesse K; Fisher, John P

2016-12-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

PubMed Central

Ball, Owen; Nguyen, Bao-Ngoc B.; Placone, Jesse K.; Fisher, John P.

2016-01-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID:27272210

Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

PubMed

Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

2011-11-01

Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine

DOE PAGES

Martino, Mikael M.; Brkic, Sime; Bovo, Emmanuela; ...

2015-04-01

In this study, blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular,more » the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.« less

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briquez, Priscilla S.; Hubbell, Jeffrey A.; Martino, Mikaël M.

2015-08-01

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localizationmore » of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.« less

Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martino, Mikael M.; Brkic, Sime; Bovo, Emmanuela

In this study, blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular,more » the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.« less

Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martino, Mikael M.; Brkic, Sime; Bovo, Emmanuela

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localizationmore » of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.« less

Biomechanics of selected arborescent and shrubby monocotyledons

PubMed Central

Haushahn, Tobias; Fink, Samuel; Speck, Thomas

2016-01-01

Main aims of the study are a deepened understanding of the mechanically relevant (ultra-)structures and the mechanical behaviour of various arborescent and shrubby monocotyledons and obtaining the structure–function relationships of different structurally conspicuous parts in Dracaena marginata stems. The stems of five different “woody” monocotyledon species were dissected and the mechanical properties of the most noticeable tissues in the five monocotyledons and, additionally, of individual vascular bundles in D. marginata, were tested under tensile stress. Results for Young’s moduli and density of these tissues were assessed as well as the area, critical strain, Young’s modulus and tensile strength of the vascular bundles in Dracaena marginata. These analyses allowed for generating a model for the mechanical interaction of tissues and vascular bundles of the stem in D. marginata as well as filling major “white spots” in property charts for biological materials. Additionally we shortly discuss the potential significance of such studies for the development of branched and unbranched bio-inspired fibre-reinforced materials and structures with enhanced properties. PMID:28144511

[Application and development of free composite tissue flap in plastic surgery].

PubMed

Lu, Kaihua; Han, Yan; Guo, Shuzhong

2007-09-01

To summarize and review the development and experience of anastomosis vascular pedicle free composite tissue flap. From July 1987 to March 2007, 321 patients with complete records were treated. Fourteen tissue flaps were applied for the repair of trauma or tumor excision defects of the body, and for organ reconstruction. Vascular crisis occurred in 20 patients within 48 hours postoperatively. Necrosis occurred at flap end in 6 patients. The total survival rate was 94.8%. The main experience was: (1) Training to grasp the basic micro-vascular anastomosis technique was very important starting up period for surgeons. The basic technique should be often practiced to ensure the safty of clinical application. (2) Restoring appearance and function were equally important in practice. (3) Utilizing the minimal invasive methods and decreasing the loss of function of donor site were important for improvement of reconstruction quality. The purpose was to achieve functional and esthetic restoration in the condition of lowest donor site scarification. The application of free composite tissue flap is important for the development of plastic surgery. There are extensive applications for free flap, especially for those critical patients. The application of free flap could decrease the mobility rate, shorten the treatment period, ease the pain of patients and improve the reconstruction effect. The experience of donor site selection, the strategy of poor recipient site condition, the advantages and disadvantages of muscle flap, the applications time, infections wound treatment and application, are helpful for the future application.

TAM receptor signaling in development.

PubMed

Burstyn-Cohen, Tal

2017-01-01

TYRO3, AXL and MERTK comprise the TAM family of receptor protein tyrosine kinases. Activated by their ligands, protein S (PROS1) and growth-arrest-specific 6 (GAS6), they mediate numerous cellular functions throughout development and adulthood. Expressed by a myriad of cell types and tissues, they have been implicated in homeostatic regulation of the immune, nervous, vascular, bone and reproductive systems. The loss-of-function of TAM signaling in adult tissues culminates in the destruction of tissue homeostasis and diseased states, while TAM gain-of-function in various tumors promotes cancer phenotypes. Combinatorial ligand-receptor interactions may elicit different molecular and cellular responses. Many of the TAM regulatory functions are essentially developmental, taking place both during embryogenesis and postnatally. This review highlights current knowledge on the role of TAM receptors and their ligands during these developmental processes in the immune, nervous, vascular and reproductive systems.

Tissue Engineered Skin and Wound Healing: Current Strategies and Future Directions.

PubMed

Bhardwaj, Nandana; Chouhan, Dimple; Mandal, Biman B

2017-01-01

The global volume of skin damage or injuries has major healthcare implications and, accounts for about half of the world's annual expenditure in the healthcare sector. In the last two decades, tissue-engineered skin constructs have shown great promise in the treatment of various skin-related disorders such as deep burns and wounds. The treatment methods for skin replacement and repair have evolved from utilization of autologous epidermal sheets to more complex bilayered cutaneous tissue engineered skin substitutes. However, inadequate vascularization, lack of flexibility in drug/growth factors loading and inability to reconstitute skin appendages such as hair follicles limits their utilization for restoration of normal skin anatomy on a routine basis. Recent advancements in cutting-edge technology from stem cell biology, nanotechnology, and various vascularization strategies have provided a tremendous springboard for researchers in developing and manipulating tissue engineered skin substitutes for improved skin regeneration and wound healing. This review summarizes the overview of skin tissue engineering and wound healing. Herein, developments and challenges of various available biomaterials, cell sources and in vitro skin models (full thickness and wound healing models) in tissue-engineered skin research are discussed. Furthermore, central to the discussion is the inclusion of various innovative strategies starting from stem cells, nanotechnology, vascularization strategies, microfluidics to three dimensional (3D) bioprinting based strategies for generation of complex skin mimics. The review then moves on to highlight the future prospects of advanced construction strategies of these bioengineered skin constructs and their contribution to wound healing and skin regeneration on current practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular controls of arterial morphogenesis

PubMed Central

Simons, Michael; Eichmann, Anne

2015-01-01

Formation of arterial vasculature, here termed arteriogenesis, is a central process in embryonic vascular development as well as in adult tissues. While the process of capillary formation, angiogenesis, is relatively well understood, much remains to be learned about arteriogenesis. Recent discoveries point to the key role played by vascular endothelial growth factor receptor 2 (VEGFR2) in control of this process and to newly identified control circuits that dramatically influence its activity. The latter can present particularly attractive targets for a new class of therapeutic agents capable of activation of this signaling cascade in a ligand-independent manner, thereby promoting arteriogenesis in diseased tissues. PMID:25953926

Tissue adaptations to gravitational stress - Newborn versus adult giraffes

NASA Technical Reports Server (NTRS)

Hargens, Alan R; Gershuni, David H.; Danzig, Larry A.; Millard, Ronald W.; Pettersson, Knut

1988-01-01

Preliminary results on developmental alterations in load-bearing tissues of newborn and adult giraffes are presented. Attention is focused on vascular wall thickness in relation to local blood pressure, and on meniscal adaptations to increased load bearing in the developing giraffe. It is believed that the developing giraffe provides an excellent model for investigations of adaptive mechanisms of increased weight bearing.

Microvascular development and growth of uterine tissue during the estrous cycle in mares.

PubMed

Ferreira-Dias, G M; Serrão, P M; Durão, J F; Silva, J R

2001-04-01

To document uterine growth and microvascular development in the endometrium of uteri with differing degrees of fibrosis as well as uterine growth throughout the estrous cycle of mares. 30 mares. Uterine tissue was obtained during the breeding season from a slaughter facility. Stage of estrous cycle of the mares was assessed on the basis of ovarian structures and plasma progesterone concentrations. Endometrium was characterized by use of light microscopy, and blood vessel walls were marked by histochemical techniques. Microvascular development was evaluated by a computerized image analysis system. Growth of uterine tissue was based on cellular content of DNA and RNA, RNA:DNA, and protein:DNA. Significant differences in vascular density were not observed in the endometrium of uteri obtained from mares euthanatized during the follicular or luteal phase of the estrous cycle, regardless of whether endometrial classification of degree of fibrosis was considered. There was a 3-fold increase in amount of DNA and RNA of endometrial cells in the follicular phase when compared to myometrium. Hypertrophy of endometrial tissue during the luteal phase was reflected by a significant increase in cell protein content and protein:DNA. Endometrial growth of vascular tissues during the estrous cycle may be coordinated with development of nonvascular tissue. Estrogen and progesterone may play a role in regulation of uterine growth and angiogenesis.

Exploiting passive nanomedicine accumulation at sites of enhanced vascular permeability for non-cancerous applications.

PubMed

Durymanov, Mikhail; Kamaletdinova, Tatiana; Lehmann, Sarah E; Reineke, Joshua

2017-09-10

Over the past few decades, enhanced permeability of tumor vasculature was actively exploited for targeted delivery of anticancer nanomedicines resulting in numerous pharmaceutical products. Formation of new immature and leaky vessels along with inflammatory remodeling of existing vessels accompany development of numerous diseases beyond cancer and present an opportunity for passive accumulation of intravenously administered nanomedicines in many pathological tissues. To date, applications of non-cancerous enhanced permeation have been relatively unexploited as target tissues and may create new therapy and prevention technologies for many disorders. Herein, we summarize the current knowledge on the nature of enhanced vascular permeability in multiple non-cancerous pathological tissues. We also discuss the clinical status of nanotherapeutics with selectivity based on passive accumulation in non-cancerous target tissues, their challenges, and prospects. Copyright © 2017 Elsevier B.V. All rights reserved.

Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution.

PubMed

Gaudiello, Emanuele; Melly, Ludovic; Cerino, Giulia; Boccardo, Stefano; Jalili-Firoozinezhad, Sasan; Xu, Lifen; Eckstein, Friedrich; Martin, Ivan; Kaufmann, Beat A; Banfi, Andrea; Marsano, Anna

2017-12-01

Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D-cell constructs. It is found that collagen sponges, which poorly bind VEGF, prevent the formation of localized hot spots of excessive concentration, therefore, precluding the development of aberrant angiogenesis despite uncontrolled expression by a genetically engineered population of adipose tissue-derived stromal cells. On the contrary, after seeding on VEGF-binding egg-white scaffolds, the same cell population caused aberrantly enlarged vascular structures after 14 d. Collagen-based engineered tissues also induced a safe and efficient angiogenesis in both the patch itself and the underlying myocardium in rat models. These findings open new perspectives on the control and the delivery of proangiogenic stimuli, and are fundamental for the vascularization of engineered tissues/organs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.

PubMed

Yamaguchi, Yukie; Kuwana, Masataka

2013-02-01

New blood vessel formation is critical, not only for organ development and tissue regeneration, but also for various pathologic processes, such as tumor development and vasculopathy. The maintenance of the postnatal vascular system requires constant remodeling, which occurs through angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is mediated by the de novo differentiation of mature endothelial cells from endothelial progenitor cells (EPCs). Early studies provided evidence that bone marrow-derived CD14⁺ monocytes can serve as a subset of EPCs because of their expression of endothelial markers and ability to promote neovascularization in vitro and in vivo. However, the current consensus is that monocytic cells do not give rise to endothelial cells in vivo, but function as support cells, by promoting vascular formation and repair through their immediate recruitment to the site of vascular injury, secretion of proangiogenic factors, and differentiation into mural cells. These monocytes that function in a supporting role in vascular repair are now termed monocytic pro-angiogenic hematopoietic cells (PHCs). Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis and microvasculopathy, along with poor vascular formation and repair. We recently showed that in patients with SSc, circulating monocytic PHCs increase dramatically and have enhanced angiogenic potency. These effects may be induced in response to defective vascular repair machinery. Since CD14⁺ monocytes can also differentiate into fibroblast-like cells that produce extracellular matrix proteins, here we propose a new hypothesis that aberrant monocytic PHCs, once mobilized into circulation, may also contribute to the fibrotic process of SSc.

Flow cytometry on the stromal-vascular fraction of white adipose tissue

USDA-ARS?s Scientific Manuscript database

Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow c...

Fusion of uniluminal vascular spheroids: a model for assembly of blood vessels

PubMed Central

Fleming, Paul A.; Argraves, W. Scott; Gentile, Carmine; Neagu, Adrian; Forgacs, Gabor; Drake, Christopher J.

2010-01-01

Here, we evaluated the self-assembly properties of uniluminal vascular spheroids having outer layers of vascular smooth muscle cells and a contiguous inner layer of endothelial cells lining a central lumen. We showed that while pairs of uniluminal vascular spheroids suspended in culture medium fused to form a larger diameter spheroidal structure, spheroids in collagen hydrogels formed elongated structures. These findings highlight the potential use of uniluminal vascular spheroids as modules to engineer blood vessels. We also demonstrate that uniluminal vascular spheroid fusion conforms to models describing the coalescence of liquid drops. Furthermore, the fusion of uniluminal vascular spheroids in vitro closely resembled the in vivo process by which the descending aorta forms from the fusion of the paired dorsal aortae during embryonic development. Together, the findings indicate that tissue liquidity underlies uniluminal vascular spheroid fusion and that in vivo anastomosis of blood vessels may involve a similar mechanism. PMID:19918756

Modeling of flow-induced shear stress applied on 3D cellular scaffolds: Implications for vascular tissue engineering.

PubMed

Lesman, Ayelet; Blinder, Yaron; Levenberg, Shulamit

2010-02-15

Novel tissue-culture bioreactors employ flow-induced shear stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex three-dimensional (3D) microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100, and 125 microm. Four inlet velocities (0.5, 1, 1.5, and 2 cm/s) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness, and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in vitro. 2009 Wiley Periodicals, Inc.

PANCREATIC TRANSPLANTATIONS IN THE SPLEEN

PubMed Central

Pratt, Joseph H.; Murphy, Fred T.

1913-01-01

Pancreatic tissue implanted in the spleen and separated from its original vascular and nervous connections can live and functionate for months. A small nodule of pancreatic tissue composed of acini without demonstrable islands of Langerhans prevented the development of diabetes. Death occurred 187 days after the extirpation of the pancreas. PMID:19867642

Role of Connective Tissue Growth Factor in the Retinal Vasculature during Development and Ischemia

PubMed Central

Pi, Liya; Xia, Huiming; Liu, Jianwen; Shenoy, Anitha K.; Hauswirth, William W.; Scott, Edward W.

2011-01-01

Purpose. To investigate the function of connective tissue growth factor (CTGF), a matricellular protein of the CCN (Cyr61/CTGF/Nov) family, in retinal vasculature during development and ischemia. Methods. CTGF expression was determined using RT-PCR, immunohistochemistry, and transgenic mice carrying CTGF promoter-driven-GFP. CTGF antibody was intraocularly injected into neonates at postnatal day (P)2, and its effect on retinal angiogenesis was analyzed at P4. Transgenic animals expressing GFP regulated by the glial fibrillary acidic protein promoter were used for astrocyte visualization. Retinal vascular occlusion was introduced by rose Bengal and laser photocoagulation on chimeric mice that were reconstituted with GFP+ bone marrow cells. Vascular repair in response to VEGF-A and CTGF was analyzed. Results. A temporal increase in CTGF at both mRNA and protein levels was observed in the ganglion cell layer and inner nuclear layer during development. Endothelial cells and pericytes were identified as the main cellular sources of CTGF during retinal angiogenesis. CTGF stimulated the migration of astrocytes, retinal endothelial cells, and pericytes in vitro. Inhibition of CTGF by specific antibody affected vascular filopodial extension, growth of the superficial vascular plexus, and astrocyte remodeling. In adult mice, CTGF was prominently expressed in the perivascular cells of arteries. CTGF activated bone marrow-derived perivascular cells and promoted fibrovascular membrane formation in the laser-induced adult retinopathy model. Conclusions. CTGF is expressed in vascular beds and acts on multiple cell types. It is important for vessel growth during early retinal development and promotes the fibrovascular reaction in murine retinal ischemia after laser injury. PMID:21969300

Converging roads: evidence for an adult hemangioblast.

PubMed

Bailey, Alexis S; Fleming, William H

2003-11-01

Classical studies of the developing embryo first suggested the existence of the hemangioblast, a precursor cell with the potential to differentiate into both blood and blood vessels. Several lines of investigation demonstrated that many of the genes activated during early hematopoietic development are also expressed in the vascular endothelium. Gene-targeting studies using embryonic stem cells have identified Flk-1, SCL, and Runx-1 as important regulatory molecules that specify both hematopoietic and vascular outcomes. Although it was anticipated that the hemangioblast would be present only during the earliest stages of vascular development in the yolk sac, accumulating evidence now indicates that hematopoietic cells with hemangioblast activity persist into adulthood. In the adult, bone marrow-derived, circulating endothelial progenitors contribute to postnatal neovascularization and enhance vascular repair following ischemic injury. Highly purified populations of hematopoietic stem cells from humans and mice can differentiate into both blood cells and vascular tissue at the single cell level. These recent findings suggest that bone marrow-derived hematopoietic stem cells or their progeny may contribute to the maintenance and repair of both the hematopoietic and the vascular systems during adult life.

A comparative study of vascular injection fluids in fresh-frozen and embalmed human cadaver forearms.

PubMed

Doomernik, D E; Kruse, R R; Reijnen, M M P J; Kozicz, T L; Kooloos, J G M

2016-10-01

Over the years, various vascular injection products have been developed to facilitate anatomical dissections. This study aimed to compare the most commonly used vascular injection products in fresh-frozen and formalin-embalmed cadaver specimens. An overview of the properties, advantages and limitations of each substance was given, and a comparison of vascular infusion procedures in both preservation methods was made. A literature search was performed in order to identify the most commonly used vascular injection products. Acrylic paint, latex, gelatin, silicone, Araldite F and Batson's No. 17 were selected for the study. One fresh-frozen and one embalmed cadaver forearm were infused with each injection product according to a uniform protocol. The curing time, skin- and subcutaneous tissue penetration, degree of filling of the arterial tree, extravasations, consistency of the injected vessels during dissection, and the costs of each injection fluid were noted. There was a large variation between the injection fluids in processing- and curing time, colour intensity, flexibility, fragility, elasticity, strength, toxicity and costs. All fluids were suitable for infusion. The penetration of injection fluid into the skin and subcutaneous tissue was significantly better in fresh-frozen specimens (P = 0.002 and P = 0.009, respectively), with significantly smaller branches casted (P = 0.004). Vascular infusion of fresh-frozen cadaver specimens results in a significantly better filled coloured arterial tree, enabling more detail to be achieved and smaller branches casted. The biomechanical properties of fresh-frozen soft tissues are less affected compared with formalin fixation. All the injection fluids studied are suitable for vascular infusion, but their different properties ensure that certain products and procedures are more suitable for specific study purposes. © 2016 Anatomical Society.

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink.

PubMed

Jia, Weitao; Gungor-Ozkerim, P Selcan; Zhang, Yu Shrike; Yue, Kan; Zhu, Kai; Liu, Wanjun; Pi, Qingment; Byambaa, Batzaya; Dokmeci, Mehmet Remzi; Shin, Su Ryon; Khademhosseini, Ali

2016-11-01

Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(ethylene glycol)-tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also have significant potentials in engineering large-scale vascularized tissue constructs towards applications in organ transplantation and repair. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Stem and progenitor cells in biostructure of blood vessel walls].

PubMed

Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

2013-09-18

Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

The pars intermedia: an anatomic basis for a coordinated vascular response to female genital arousal.

PubMed

Shih, Cheryl; Cold, Christopher J; Yang, Claire C

2013-06-01

The pars intermedia is an area of the vulva that has been inconsistently described in the literature. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Histologic ultrastructural description of the pars intermedia. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. © 2012 International Society for Sexual Medicine.

Caffeine's Vascular Mechanisms of Action

PubMed Central

Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

2010-01-01

Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

Engineering clinically relevant volumes of vascularized bone.

PubMed

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-05-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A PEGylated platelet free plasma hydrogel based composite scaffold enables stable vascularization and targeted cell delivery for volumetric muscle loss.

PubMed

Aurora, Amit; Wrice, Nicole; Walters, Thomas J; Christy, Robert J; Natesan, Shanmugasundaram

2018-01-01

Extracellular matrix (ECM) scaffolds are being used for the clinical repair of soft tissue injuries. Although improved functional outcomes have been reported, ECM scaffolds show limited tissue specific remodeling response with concomitant deposition of fibrotic tissue. One plausible explanation is the regression of blood vessels which may be limiting the diffusion of oxygen and nutrients across the scaffold. Herein we develop a composite scaffold as a vasculo-inductive platform by integrating PEGylated platelet free plasma (PFP) hydrogel with a muscle derived ECM scaffold (m-ECM). In vitro, adipose derived stem cells (ASCs) seeded onto the composite scaffold differentiated into two distinct morphologies, a tubular network in the hydrogel, and elongated structures along the m-ECM scaffold. The composite scaffold showed a high expression of ITGA5, ITGB1, and FN and a synergistic up-regulation of ang1 and tie-2 transcripts. The in vitro ability of the composite scaffold to provide extracellular milieu for cell adhesion and molecular cues to support vessel formation was investigated in a rodent volumetric muscle loss (VML) model. The composite scaffold delivered with ASCs supported robust and stable vascularization. Additionally, the composite scaffold supported increased localization of ASCs in the defect demonstrating its ability for localized cell delivery. Interestingly, ASCs were observed homing in the injured muscle and around the perivascular space possibly to stabilize the host vasculature. In conclusion, the composite scaffold delivered with ASCs presents a promising approach for scaffold vascularization. The versatile nature of the composite scaffold also makes it easily adaptable for the repair of soft tissue injuries. Decellularized extracellular matrix (ECM) scaffolds when used for soft tissue repair is often accompanied by deposition of fibrotic tissue possibly due to limited scaffold vascularization, which limits the diffusion of oxygen and nutrients across the scaffold. Although a variety of scaffold vascularization strategies has been investigated, their limitations preclude rapid clinical translation. In this study we have developed a composite scaffold by integrating bi-functional polyethylene glycol modified platelet free plasma (PEGylated PFP) with adipose derived stem cells (ASCs) along with a muscle derived ECM scaffold (m-ECM). The composite scaffold provides a vasculo-inductive and an effective cell delivery platform for volumetric muscle loss. Copyright © 2017 Acta Materialia Inc. All rights reserved.

Vascular Endothelial Cell-Specific Connective Tissue Growth Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary Hypertension.

PubMed

Pi, Liya; Fu, Chunhua; Lu, Yuanquing; Zhou, Junmei; Jorgensen, Marda; Shenoy, Vinayak; Lipson, Kenneth E; Scott, Edward W; Bryant, Andrew J

2018-01-01

Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown. In this study, we generated a transgenic mouse line in which the Ctgf gene was floxed and deleted in vascular endothelial cells that expressed Cre recombinase under the control of VE-Cadherin promoter (eCTGF KO mice). Lack of vascular endothelial-derived CTGF protected against the development of PH secondary to chronic hypoxia, as well as in another model of bleomycin-induced pulmonary hypertension. Importantly, attenuation of PH was associated with a decrease in infiltrating inflammatory cells expressing CD11b or integrin α M (ITGAM), a known adhesion receptor for CTGF, in the lungs of hypoxia-exposed eCTGF KO mice. Moreover, these pathological changes were associated with activation of-Rho GTPase family member-cell division control protein 42 homolog (Cdc42) signaling, known to be associated with alteration in endothelial barrier function. These data indicate that endothelial-specific deletion of CTGF results in protection against development of chronic-hypoxia induced PH. This protection is conferred by both a decrease in inflammatory cell recruitment to the lung, and a reduction in lung Cdc42 activity. Based on our studies, CTGF inhibitor treatment should be investigated in patients with PH associated with chronic hypoxia secondary to chronic lung disease.

MR-guided endovascular interventions: a comprehensive review on techniques and applications.

PubMed

Kos, Sebastian; Huegli, Rolf; Bongartz, Georg M; Jacob, Augustinus L; Bilecen, Deniz

2008-04-01

The magnetic resonance (MR) guidance of endovascular interventions is probably one of the greatest challenges of clinical MR research. MR angiography is not only an imaging tool for the vasculature but can also simultaneously depict high tissue contrast, including the differentiation of the vascular wall and perivascular tissues, as well as vascular function. Several hurdles had to be overcome to allow MR guidance for endovascular interventions. MR hardware and sequence design had to be developed to achieve acceptable patient access and to allow real-time or near real-time imaging. The development of interventional devices, both applicable and safe for MR imaging (MRI), was also mandatory. The subject of this review is to summarize the latest developments in real-time MRI hardware, MRI, visualization tools, interventional devices, endovascular tracking techniques, actual applications and safety issues.

Genetic and hormonal regulation of cambial development.

PubMed

Ursache, Robertas; Nieminen, Kaisa; Helariutta, Ykä

2013-01-01

The stems and roots of most dicot plants increase in diameter by radial growth, due to the activity of secondary meristems. Two types of meristems function in secondary plant body formation: the vascular cambium, which gives rise to secondary xylem and phloem, and the cork cambium, which produces a bark layer that replaces the epidermis and protects the plant stem from mechanical damage and pathogens. Cambial development, the initiation and activity of the vascular cambium, leads to an accumulation of wood, the secondary xylem tissue. The thick, cellulose-rich cell walls of wood provide a source of cellulose and have the potential to be used as a raw material for sustainable and renewable energy production. In this review, we will discuss what is known about the mechanisms regulating the cambium and secondary tissue development. Copyright © Physiologia Plantarum 2012.

The chicken chorioallantoic membrane model in biology, medicine and bioengineering

PubMed Central

Nowak-Sliwinska, Patrycja; Segura, Tatiana; Iruela-Arispe, M. Luisa

2015-01-01

The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has been shared by specialists working in bioengineering, development, morphology, biochemistry, transplant biology, cancer research and drug development. The tissue composition and accessibility of the CAM for experimental manipulation, makes it an attractive preclinical in vivo model for drug screening and / or for studies of vascular growth. In this article we provide a detailed review of the use of the CAM to study vascular biology and response of blood vessels to a variety of agonists. We also present distinct cultivation protocols discussing their advantages and limitations and provide a summarized update on the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and toxicology. PMID:25138280

Bioreactor-induced mesenchymal progenitor cell differentiation and elastic fiber assembly in engineered vascular tissues.

PubMed

Lin, Shigang; Mequanint, Kibret

2017-09-01

In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components similar to native arteries. To this end, the aim of the current study was to fabricate 4mm inner diameter vascular tissues using mesenchymal progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating either in perfusion or pulsatile perfusion mode was used to generate physiological-like stimuli to promote progenitor cell differentiation, extracellular elastin production, and tissue maturation. Our data demonstrated that pulsatile forces and perfusion of 3D tubular constructs from both the lumenal and ablumenal sides with culture media significantly improved tissue assembly, effectively inducing mesenchymal progenitor cell differentiation to SMCs with contemporaneous elastin production. With bioreactor cultivation, progenitor cells differentiated toward smooth muscle lineage characterized by the expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly, pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin and its extracellular cross-linking into elastic fiber compared with static culture controls. Taken together, the current study demonstrated progenitor cell differentiation and vascular tissue assembly, and provides insights into elastin synthesis and assembly to fibers. Incorporation of elastin into engineered vascular tissues represents a critical design goal for both mechanical and biological functions. In the present study, we seeded porous tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by bioreactor not only induced mesenchymal progenitor cell differentiation to vascular smooth muscle lineage but also actively promoted elastin synthesis and fiber assembly. Gene expression and protein synthesis analyses coupled with histological and immunofluorescence staining revealed that elastin-containing vascular tissues were fabricated. More importantly, co-localization and co-immunoprecipitation experiments demonstrated that elastin and fibrillin-1 were abundant throughout the cross-section of the tissue constructs suggesting a process of elastin protein crosslinking. This study paves a way forward to engineer elastin-containing functional vascular substitutes from multipotent progenitor cells in a bioreactor. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Regulation of plant vascular stem cells by endodermis-derived EPFL-family peptide hormones and phloem-expressed ERECTA-family receptor kinases.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2013-12-01

Plant vasculatures are complex tissues consisting of (pro)cambium, phloem, and xylem. The (pro)cambium serves as vascular stem cells that produce all vascular cells. The Arabidopsis ERECTA (ER) receptor kinase is known to regulate the architecture of inflorescence stems. It was recently reported that the er mutation enhances a vascular phenotype induced by a mutation of TDR/PXY, which plays a significant role in procambial proliferation, suggesting that ER participates in vascular development. However, detailed molecular mechanisms of the ER-dependent vascular regulation are largely unknown. Here, this work found that ER and its paralogue, ER-LIKE1, were redundantly involved in procambial development of inflorescence stems. Interestingly, their activity in the phloem was sufficient for vascular regulation. Furthermore, two endodermis-derived peptide hormones, EPFL4 and EPFL6, were redundantly involved in such regulation. It has been previously reported that EPFL4 and EPFL6 act as ligands of phloem-expressed ER for stem elongation. Therefore, these findings indicate that cell-cell communication between the endodermis and the phloem plays an important role in procambial development as well as stem elongation. Interestingly, similar EPFL-ER modules control two distinct developmental events by slightly changing their components: the EPFL4/6-ER module for stem elongation and the EPFL4/6-ER/ERL1 module for vascular development.

3D bioprinting of biomimetic aortic vascular constructs with self-supporting cells.

PubMed

Kucukgul, Can; Ozler, S Burce; Inci, Ilyas; Karakas, Ezgi; Irmak, Ster; Gozuacik, Devrim; Taralp, Alpay; Koc, Bahattin

2015-04-01

Cardiovascular diseases are the leading cause of deaths throughout the world. Vascular diseases are mostly treated with autografts and blood vessel transplantations. However, traditional grafting methods have several problems including lack of suitable harvest sites, additional surgical costs for harvesting procedure, pain, infection, lack of donors, and even no substitutes at all. Recently, tissue engineering and regenerative medicine approaches are used to regenerate damaged or diseased tissues. Most of the tissue engineering investigations have been based on the cell seeding into scaffolds by providing a suitable environment for cell attachment, proliferation, and differentiation. Because of the challenges such as difficulties in seeding cells spatially, rejection, and inflammation of biomaterials used, the recent tissue engineering studies focus on scaffold-free techniques. In this paper, the development of novel computer aided algorithms and methods are developed for 3D bioprinting of scaffold-free biomimetic macrovascular structures. Computer model mimicking a real human aorta is generated using imaging techniques and the proposed computational algorithms. An optimized three-dimensional bioprinting path planning are developed with the proposed self-supported model. Mouse embryonic fibroblast (MEF) cell aggregates and support structures (hydrogels) are 3D bioprinted layer-by-layer according to the proposed self-supported method to form an aortic tissue construct. © 2014 Wiley Periodicals, Inc.

Non-contact hematoma damage and healing assessment using reflectance photoplethysmographic imaging

NASA Astrophysics Data System (ADS)

Amelard, Robert; Pfisterer, Kaylen J.; Clausi, David A.; Wong, Alexander

2016-03-01

Impact trauma may cause a hematoma, which is the leakage of venous blood into surrounding tissues. Large hematomas can be dangerous as they may inhibit local blood ow. Hematomas are often diagnosed visually, which may be problematic if the hematoma leaks deeper than the visible penetration depth. Furthermore, vascular wound healing is often monitored at home without the aid of a clinician. We therefore investigated the use of near infrared (NIR) re ectance photoplethysmographic imaging (PPGI) to assess vascular damage resulting from a hematoma, and monitor the healing process. In this case study, the participant experienced internal vascular damage in the form of a hematoma. Using a PPGI system with dual-mode temporally coded illumination for ambient-agnostic data acquisition and mounted optical elements, the tissue was illuminated with a spatially uniform irradiance pattern of 850 nm wavelength light for increased tissue penetration and high oxy-to-deoxyhemoglobin absorption ratio. Initial and follow-up PPGI data collection was performed to assess vascular damage and healing. The tissue PPGI sequences were spectrally analyzed, producing spectral maps of the tissue area. Experimental results show that spatial differences in spectral information can be observed around the damaged area. In particular, the damaged site exhibited lower pulsatility than the surrounding healthy tissue. This pulsatility was largely restored in the follow-up data, suggesting that the tissue had undergone vascular healing. These results indicate that hematomas can be assessed and monitored in a non-contact visual manner, and suggests that PPGI can be used for tissue health assessment, with potential extensions to peripheral vascular disease.

Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts?

PubMed

Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Karayannopoulou, Georgia; Buron, Fannie; Dubois, Valérie; Thaunat, Olivier; Badet, Lionel; Morelon, Emmanuel

2016-04-01

Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection.

Thermal Inkjet Printing in Tissue Engineering and Regenerative Medicine

PubMed Central

Cui, Xiaofeng; Boland, Thomas; D’Lima, Darryl D.; Lotz, Martin K.

2013-01-01

With the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the desired 2D and 3D locations, bioprinting has great potential to develop promising approaches in translational medicine and organ replacement. The most recent advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review. Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction. With layer-by-layer assembly, 3D tissues with complex structures can be printed using scanned CT or MRI images. Vascular or nerve systems can be enabled simultaneously during the organ construction with digital control. Therefore, bioprinting is the only solution to solve this critical issue in thick and complex tissues fabrication with vascular system. Collectively, bioprinting based on thermal inkjet has great potential and broad applications in tissue engineering and regenerative medicine. This review article introduces some important patents related to bioprinting living systems and the bioprinting in tissue engineering field. PMID:22436025

Molecular controls of arterial morphogenesis.

PubMed

Simons, Michael; Eichmann, Anne

2015-05-08

Formation of arterial vasculature, here termed arteriogenesis, is a central process in embryonic vascular development as well as in adult tissues. Although the process of capillary formation, angiogenesis, is relatively well understood, much remains to be learned about arteriogenesis. Recent discoveries point to the key role played by vascular endothelial growth factor receptor 2 in control of this process and to newly identified control circuits that dramatically influence its activity. The latter can present particularly attractive targets for a new class of therapeutic agents capable of activation of this signaling cascade in a ligand-independent manner, thereby promoting arteriogenesis in diseased tissues. © 2015 American Heart Association, Inc.

Estimates of plasma, packed cell and total blood volume in tissues of the rainbow trout (Salmo gairdneri)

USGS Publications Warehouse

Gingerich, W.H.; Pityer, R.A.; Rach, J.J.

1987-01-01

1. Total blood volume and relative blood volumes in selected tissues were determined in non-anesthetized, confined rainbow trout by using 51Cr-labelled trout erythrocytes as a vascular space marker.2. Mean total blood volume was estimated to be 4.09 ± 0.55 ml/100 g, or about 75% of that estimated with the commonly used plasma space marker Evans blue dye.3. Relative tissue blood volumes were greatest in highly perfused tissues such as kidney, gills, brain and liver and least in mosaic muscle.4. Estimates of tissue vascular spaces, made using radiolabelled erythrocytes, were only 25–50% of those based on plasma space markers.5. The consistently smaller vascular volumes obtained with labelled erythrocytes could be explained by assuming that commonly used plasma space markers diffuse from the vascular compartment.

Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels

PubMed Central

Somo, Sami I.; Akar, Banu; Bayrak, Elif S.; Larson, Jeffery C.; Appel, Alyssa A.; Mehdizadeh, Hamidreza; Cinar, Ali

2015-01-01

Rapid and controlled vascularization within biomaterials is essential for many applications in regenerative medicine. The extent of vascularization is influenced by a number of factors, including scaffold architecture. While properties such as pore size and total porosity have been studied extensively, the importance of controlling the interconnectivity of pores has received less attention. A sintering method was used to generate hydrogel scaffolds with controlled pore interconnectivity. Poly(methyl methacrylate) microspheres were used as a sacrificial agent to generate porous poly(ethylene glycol) diacrylate hydrogels with interconnectivity varying based on microsphere sintering conditions. Interconnectivity levels increased with sintering time and temperature with resultant hydrogel structure showing agreement with template structure. Porous hydrogels with a narrow pore size distribution (130–150 μm) and varying interconnectivity were investigated for their ability to influence vascularization in response to gradients of platelet-derived growth factor-BB (PDGF-BB). A rodent subcutaneous model was used to evaluate vascularized tissue formation in the hydrogels in vivo. Vascularized tissue invasion varied with interconnectivity. At week 3, higher interconnectivity hydrogels had completely vascularized with twice as much invasion. Interconnectivity also influenced PDGF-BB transport within the scaffolds. An agent-based model was used to explore the relative roles of steric and transport effects on the observed results. In conclusion, a technique for the preparation of hydrogels with controlled pore interconnectivity has been developed and evaluated. This method has been used to show that pore interconnectivity can independently influence vascularization of biomaterials. PMID:25603533

The structure-mechanical relationship of palm vascular tissue.

PubMed

Wang, Ningling; Liu, Wangyu; Huang, Jiale; Ma, Ke

2014-08-01

The structure-mechanical relationship of palm sheath is studied with numerical and experimental methods. The cellular structure of the vascular tissue is rebuilt with an image-based reconstruction method and used to create finite element models. The validity of the models is firstly verified with the results from the tensile tests. Then, the cell walls inside each of the specific regions (fiber cap, vessel, xylem, etc.) are randomly removed to obtain virtually imperfect structures. By comparing the magnitudes of performance degradation in the different imperfect structures, the influences of each region on the overall mechanical performances of the vascular tissue are discussed. The longitudinal stiffness and yield strength are sensitive to the defects in the vessel regions. While in the transverse directions (including the radial and tangential directions), the parenchymatous tissue determines the mechanical properties of the vascular tissue. Moreover, the hydraulic, dynamic response and energy absorption behavior of the vascular tissue are numerically explored. The flexibility of natural palm tissue enhances its impact resistance. Under the quasi-static compression, the cell walls connecting the fiber cap and the vessel dissipate more energy. The dominant role of the fiber cap in the plastic energy dissipation under high-speed impact is observed. And the radially-arranged fiber cap also allows the palm tissue to improve its tangential mechanical performances under hydraulic pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bronchus-associated Lymphoid Tissue in Pulmonary Hypertension Produces Pathologic Autoantibodies

PubMed Central

Colvin, Kelley L.; Cripe, Patrick J.; Ivy, D. Dunbar; Stenmark, Kurt R.

2013-01-01

Rationale: Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. Objectives: We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. Methods: We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Measurements and Main Results: Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3+ T cells over a core of CD45RA+ B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1+ high endothelial venules and vascular cell adhesion molecule–positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Conclusions: Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue–directed therapies may be beneficial in treating pulmonary hypertension. PMID:24093638

A Computational Model Predicting Disruption of Blood Vessel Development

EPA Science Inventory

Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a varie...

Design of tissue engineering scaffolds based on hyperbolic surfaces: structural numerical evaluation.

PubMed

Almeida, Henrique A; Bártolo, Paulo J

2014-08-01

Tissue engineering represents a new field aiming at developing biological substitutes to restore, maintain, or improve tissue functions. In this approach, scaffolds provide a temporary mechanical and vascular support for tissue regeneration while tissue in-growth is being formed. These scaffolds must be biocompatible, biodegradable, with appropriate porosity, pore structure and distribution, and optimal vascularization with both surface and structural compatibility. The challenge is to establish a proper balance between porosity and mechanical performance of scaffolds. This work investigates the use of two different types of triple periodic minimal surfaces, Schwarz and Schoen, in order to design better biomimetic scaffolds with high surface-to-volume ratio, high porosity and good mechanical properties. The mechanical behaviour of these structures is assessed through the finite element method software Abaqus. The effect of two parametric parameters (thickness and surface radius) is also evaluated regarding its porosity and mechanical behaviour. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice

PubMed Central

Agrawal, Vijayendra; Maharjan, Sony; Kim, Kyeojin; Kim, Nam-Jung; Son, Jimin; Lee, Keunho; Choi, Hyun-Jung; Rho, Seung-Sik; Ahn, Sunjoo; Won, Moo-Ho; Ha, Sang-Jun; Koh, Gou Young; Kim, Young-Myeong; Suh, Young-Ger; Kwon, Young-Guen

2014-01-01

Tumor blood vessels are leaky and immature, which causes inadequate blood supply to tumor tissues resulting in hypoxic microenvironment and promotes metastasis. Here we have explored tumor vessel modulating activity of Sac-1004, a recently developed molecule in our lab, which directly potentiates VE-cadherin-mediated endothelial cell junction. Sac-1004 could enhance vascular junction integrity in tumor vessels and thereby inhibit vascular leakage and enhance vascular perfusion. Improved perfusion enabled Sac-1004 to have synergistic anti-tumor effect on cisplatin-mediated apoptosis of tumor cells. Interestingly, characteristics of normalized blood vessels namely reduced hypoxia, improved pericyte coverage and decreased basement membrane thickness were readily observed in tumors treated with Sac-1004. Remarkably, Sac-1004 was also able to inhibit lung and lymph node metastasis in MMTV and B16BL6 tumor models. This was in correlation with a reduction in epithelial-to-mesenchymal transition of tumor cells with considerable diminution in expression of related transcription factors. Moreover, cancer stem cell population dropped substantially in Sac-1004 treated tumor tissues. Taken together, our results showed that direct restoration of vascular junction could be a significant strategy to induce normalization of tumor blood vessels and reduce metastasis. PMID:24811731

Auxin Influx Carriers Control Vascular Patterning and Xylem Differentiation in Arabidopsis thaliana

PubMed Central

Siligato, Riccardo; Alonso, Jose M.; Swarup, Ranjan; Bennett, Malcolm J.; Mähönen, Ari Pekka; Caño-Delgado, Ana I.; Ibañes, Marta

2015-01-01

Auxin is an essential hormone for plant growth and development. Auxin influx carriers AUX1/LAX transport auxin into the cell, while auxin efflux carriers PIN pump it out of the cell. It is well established that efflux carriers play an important role in the shoot vascular patterning, yet the contribution of influx carriers to the shoot vasculature remains unknown. Here, we combined theoretical and experimental approaches to decipher the role of auxin influx carriers in the patterning and differentiation of vascular tissues in the Arabidopsis inflorescence stem. Our theoretical analysis predicts that influx carriers facilitate periodic patterning and modulate the periodicity of auxin maxima. In agreement, we observed fewer and more spaced vascular bundles in quadruple mutants plants of the auxin influx carriers aux1lax1lax2lax3. Furthermore, we show AUX1/LAX carriers promote xylem differentiation in both the shoot and the root tissues. Influx carriers increase cytoplasmic auxin signaling, and thereby differentiation. In addition to this cytoplasmic role of auxin, our computational simulations propose a role for extracellular auxin as an inhibitor of xylem differentiation. Altogether, our study shows that auxin influx carriers AUX1/LAX regulate vascular patterning and differentiation in plants. PMID:25922946

Stem development through vascular tissues: EPFL-ERECTA family signaling that bounces in and out of phloem.

PubMed

Tameshige, Toshiaki; Ikematsu, Shuka; Torii, Keiko U; Uchida, Naoyuki

2017-01-01

Plant cells communicate with each other using a variety of signaling molecules. Recent studies have revealed that various types of secreted peptides, as well as phytohormones known since long ago, mediate cell-cell communication in diverse contexts of plant life. These peptides affect cellular activities, such as proliferation and cell fate decisions, through their perception by cell surface receptors located on the plasma membrane of target cells. ERECTA (ER), an Arabidopsis thaliana receptor kinase gene, was first identified as a stem growth regulator, and since then an increasing number of studies have shown that ER is involved in a wide range of developmental and physiological processes. In particular, molecular functions of ER have been extensively studied in stomatal patterning. Furthermore, the importance of ER signaling in vascular tissues of inflorescence stems, especially in phloem cells, has recently been highlighted. In this review article, first we briefly summarize the history of ER research including studies on stomatal development, then introduce ER functions in vascular tissues, and discuss its interactions with phytohormones and other receptor kinase signaling pathways. Future questions and challenges will also be addressed. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Design and evaluation of a novel subatmospheric pressure bioreactor for the preconditioning of tissue-engineered vascular constructs.

PubMed

Coakley, Daniel N; Shaikh, Faisal M; O'Sullivan, Kathleen; Kavanagh, Eamon G; Grace, Pierce A; McGloughlin, Tim M

2016-02-01

The pre-conditioning of tissue-engineered vascular scaffolds with mechanical stimuli is being recognised as an essential step in producing a functional vascular construct. In this study we design and evaluate a novel bioreactor, which exerts a mechanical strain on developing vascular scaffolds via subatmospheric pressure. We design and construct a bioreactor, which exerts subatmospheric pressure via a vacuum assisted closure unit. Vascular scaffolds seeded with human umbilical endothelial cells were evaluated for structural integrity, microbial contamination, cellular viability, von Willebrand factor (VWF) production, cell proliferation and morphology under a range of subatmospheric pressures (75-200mmHg). The bioreactor produced sustained subatmospheric pressures, which exerted a mechanical strain on the vascular scaffold. No microbial contamination was found during the study. The structural integrity of the vascular construct was maintained. There was no difference in cellular viability between control or subatmospheric pressure groups (p = 0.817). Cells continued to produce VWF under a range of subatmospheric pressures. Cells subjected to subatmospheric pressures of 125mmHg and 200mmHg exhibited higher levels of growth than cells in atmospheric pressure at 24 (p≤0.016) and 48 hour (p≤0.001). Negative pressure affected cellular morphology, which were more organised, elongated and expanded when exposed to subatmospheric pressure. We have constructed and validated a novel subatmospheric bioreactor. The bioreactor maintained a continuous subatmospheric pressure to the vascular scaffolds in a stable, sterile and constant environment. The bioreactor exerted a strain on the vascular sheets, which was shown to alter cellular morphology and enhance cellular proliferation.

Induction of vascular endothelial phenotype and cellular proliferation from human cord blood stem cells cultured in simulated microgravity

NASA Astrophysics Data System (ADS)

Chiu, Brian; Z-M Wan, Jim; Abley, Doris; Akabutu, John

2005-05-01

Recent studies have demonstrated that stem cells derived from adult hematopoietic tissues are capable of trans-differentiation into non-hematopoietic cells, and that the culture in microgravity ( μg) may modulate the proliferation and differentiation. We investigated the application of μg to human umbilical cord blood stem cells (CBSC) in the induction of vascular endothelial phenotype expression and cellular proliferation. CD34+ mononuclear cells were isolated from waste human umbilical cord blood samples and cultured in simulated μg for 14 days. The cells were seeded in rotary wall vessels (RWV) with or without microcarrier beads (MCB) and vascular endothelial growth factor was added during culture. Controls consisted of culture in 1 G. The cell cultures in RWV were examined by inverted microscopy. Cell counts, endothelial cell and leukocyte markers performed by flow-cytometry and FACS scan were assayed at days 1, 4, 7 and at the termination of the experiments. Culture in RWV revealed significantly increased cellular proliferation with three-dimensional (3D) tissue-like aggregates. At day 4, CD34+ cells cultured in RWV bioreactor without MCB developed vascular tubular assemblies and exhibited endothelial phenotypic markers. These data suggest that CD34+ human umbilical cord blood progenitors are capable of trans-differentiation into vascular endothelial cell phenotype and assemble into 3D tissue structures. Culture of CBSC in simulated μg may be potentially beneficial in the fields of stem cell biology and somatic cell therapy.

Laser-guided direct writing for three-dimensional tissue engineering: Analysis and application of radiation forces

NASA Astrophysics Data System (ADS)

Nahmias, Yaakov Koby

Tissue Engineering aims for the creation of functional tissues or organs using a combination of biomaterials and living cells. Artificial tissues can be implanted in patients to restore tissue function that was lost due to trauma, disease, or genetic disorder. Tissue equivalents may also be used to screen the effects of drugs and toxins, reducing the use of animals in research. One of the principle limitations to the size of engineered tissue is oxygen and nutrient transport. Lacking their own vascular bed, cells embedded in the engineered tissue will consume all available oxygen within hours while out branching blood vessels will take days to vascularize the implanted tissue. Establishing capillaries within the tissue prior to implantation can potentially eliminate this limitation. One approach to establishing capillaries within the tissue is to directly write endothelial cells with micrometer accuracy as it is being built. The patterned endothelial cells will then self-assemble into vascular structures within the engineering tissue. The cell patterning technique known as laser-guided direct writing can confine multiple cells in a laser beam and deposit them as a steady stream on any non-absorbing surface with micrometer scale accuracy. By applying the generalized Lorenz-Mie theory for light scattering on laser-guided direct writing we were able to accurately predict the behavior of with various cells and particles in the focused laser. In addition, two dimensionless parameters were identified for general radiation-force based system design. Using laser-guided direct writing we were able to direct the assembly of endothelial vascular structures with micrometer accuracy in two and three dimensions. The patterned vascular structures provided the backbone for subsequent in vitro liver morphogenesis. Our studies show that hepatocytes migrate toward and adhere to endothelial vascular structures in response to endothelial-secreted hepatocyte growth factor (HGF). Our approach has the advantage of retaining the natural heterotypic cell-cell interaction and spatial arrangement of native tissue, which is important for proper tissue function.* *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Microsoft Office; Windows MediaPlayer or RealPlayer.

Adenosine triphosphate as a molecular mediator of the vascular response to injury.

PubMed

Guth, Christy M; Luo, Weifung; Jolayemi, Olukemi; Chadalavada, Kalyan S; Komalavilas, Padmini; Cheung-Flynn, Joyce; Brophy, Colleen M

2017-08-01

Human saphenous veins used for arterial bypass undergo stretch injury at the time of harvest and preimplant preparation. Vascular injury promotes intimal hyperplasia, the leading cause of graft failure, but the molecular events leading to this response are largely unknown. This study investigated adenosine triphosphate (ATP) as a potential molecular mediator in the vascular response to stretch injury, and the downstream effects of the purinergic receptor, P2X7R, and p38 MAPK activation. A subfailure stretch rat aorta model was used to determine the effect of stretch injury on release of ATP and vasomotor responses. Stretch-injured tissues were treated with apyrase, the P2X7R antagonist, A438079, or the p38 MAPK inhibitor, SB203580, and subsequent contractile forces were measured using a muscle bath. An exogenous ATP (eATP) injury model was developed and the experiment repeated. Change in p38 MAPK phosphorylation after stretch and eATP tissue injury was determined using Western blotting. Noninjured tissue was incubated in the p38 MAPK activator, anisomycin, and subsequent contractile function and p38 MAPK phosphorylation were analyzed. Stretch injury was associated with release of ATP. Contractile function was decreased in tissue subjected to subfailure stretch, eATP, and anisomycin. Contractile function was restored by apyrase, P2X7R antagonism, and p38-MAPK inhibition. Stretch, eATP, and anisomycin-injured tissue demonstrated increased phosphorylation of p38 MAPK. Taken together, these data suggest that the vascular response to stretch injury is associated with release of ATP and activation of the P2X7R/P38 MAPK pathway, resulting in contractile dysfunction. Modulation of this pathway in vein grafts after harvest and before implantation may reduce the vascular response to injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Optical Histology: High-Resolution Visualization of Tissue Microvasculature

NASA Astrophysics Data System (ADS)

Moy, Austin Jing-Ming

Mammalian tissue requires the delivery of nutrients, growth factors, and the exchange of oxygen and carbon dioxide gases to maintain normal function. These elements are delivered by the blood, which travels through the connected network of blood vessels, known as the vascular system. The vascular system consists of large feeder blood vessels (arteries and veins) that are connected to the small blood vessels (arterioles and venules), which in turn are connected to the capillaries that are directly connected to the tissue and facilitate gas exchange and nutrient delivery. These small blood vessels and capillaries make up an intricate but organized network of blood vessels that exist in all mammalian tissues known as the microvasculature and are very important in maintaining the health and proper function of mammalian tissue. Due to the importance of the microvasculature in tissue survival, disruption of the microvasculature typically leads to tissue dysfunction and tissue death. The most prevalent method to study the microvasculature is visualization. Immunohistochemistry (IHC) is the gold-standard method to visualize tissue microvasculature. IHC is very well-suited for highly detailed interrogation of the tissue microvasculature at the cellular level but is unwieldy and impractical for wide-field visualization of the tissue microvasculature. The objective my dissertation research was to develop a method to enable wide-field visualization of the microvasculature, while still retaining the high-resolution afforded by optical microscopy. My efforts led to the development of a technique dubbed "optical histology" that combines chemical and optical methods to enable high-resolution visualization of the microvasculature. The development of the technique first involved preliminary studies to quantify optical property changes in optically cleared tissues, followed by development and demonstration of the methodology. Using optical histology, I successfully obtained high resolution, depth sectioned images of the microvasculature in mouse brain and the coronary microvasculature in mouse heart. Future directions of optical histology include the potential to facilitate visualization of the entire microvascular structure of an organ as well as visualization of other tissue molecular markers of interest.

Photoacoustic imaging of vascular networks in transgenic mice

NASA Astrophysics Data System (ADS)

Laufer, J. G.; Cleary, J. O.; Zhang, E. Z.; Lythgoe, M. F.; Beard, P. C.

2010-02-01

The preferential absorption of near infrared light by blood makes photoacoustic imaging well suited to visualising vascular structures in soft tissue. In addition, the spectroscopic specificity of tissue chromophores can be exploited by acquiring images at multiple excitation wavelengths. This allows the quantification of endogenous chromophores, such as oxy- and deoxyhaemoglobin, and hence blood oxygenation, and the detection of exogenous chromophores, such as functionalised contrast agents. More importantly, this approach has the potential to visualise the spatial distribution of low concentrations of functionalised contrast agents against the strong background absorption of the endogenous chromophores. This has a large number of applications in the life sciences. One example is the structural and functional phenotyping of transgenic mice for the study of the genetic origins of vascular malformations, such as heart defects. In this study, photoacoustic images of mouse embryos have been acquired to study the development of the vasculature following specific genetic knockouts.

Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for auricular vascularized composite tissue engineering.

PubMed

Duisit, Jérôme; Amiel, Hadrien; Wüthrich, Tsering; Taddeo, Adriano; Dedriche, Adeline; Destoop, Vincent; Pardoen, Thomas; Bouzin, Caroline; Joris, Virginie; Magee, Derek; Vögelin, Esther; Harriman, David; Dessy, Chantal; Orlando, Giuseppe; Behets, Catherine; Rieben, Robert; Gianello, Pierre; Lengelé, Benoît

2018-06-01

Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors, providing a perfusable matrix that retains the ear's original complexity and hosts new viable cells after seeding. This approach unlocks the ability to achieve an auricular tissue engineering approach, associated with possible clinical translation. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques.

PubMed

Spadaccio, Cristiano; Nappi, Francesco; De Marco, Federico; Sedati, Pietro; Sutherland, Fraser W H; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto

2016-01-01

In this study, we tested in vivo effectiveness of a previously developed poly-l-lactide/poly-ε-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings.

[Expression of OPG/RANK/RANKL in the rat dental pulp tissue of periodontitis combined with vascular calcification and its clinical significance].

PubMed

Pan, Ke-Qing; Zhang, Peng-Mei; Deng, Jing; Lou, Xiu-Xiu; Meng, Yun; Liu, Gui-Rong

2016-08-01

To study the expression and possible role of OPG/RANK/RANKLin the rat dental pulp of periodontitis combined with vascular calcification. Thirty-six male Wister rats were randomly divided into 4 groups: control group(group C), periodontitis group(group CP), vascular calcification group(group VDN) and compound group(group CP+VDN). Each group underwent corresponding management to establish animal model. When the model was successful, the maxillae including molars were sectioned, pulp tissue was examined by H-E staining; Immunohistochemical staining method was used to evaluate the expression and ratio of OPG and RANKL in pulp tissues. Statistical analysis was carried out using SPSS 19.0 software package. The pulp tissue of group CP, VDN, CP+VDN showed varied degrees of damage, neutrophil infiltration, pulp vascular congestion, odontoblasts vacuolar changes, pulp necrosis by H-E staining, and the changes in CP+VDN group was the most significant, followed by CP group, VDN group. Immunohistochemistry showed OPG in pulp tissues in group CP, VDN, CP+VDN were significantly lower than that in normal group (P<0.05), and the expression in group CP+VDN was the least;Expression of RANKL in pulp tissues in group CP, VDN, CP+VDN were significantly higher than that in normal group(P<0.05)，and the expression in group CP+VDN was the highest. The ratio of OPG/RANKL in normal group was the highest, and the ratio in CP+VDN group was the lowest. Periodontitis and vascular calcification can damage the pulp tissue, periodontitis compound with vascular calcification may aggravate the injury; OPG/RANKL/RANK system may play an important role in pulp tissue injury.

Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

PubMed

Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

2015-12-01

In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Positioning Bascularized Composite Allotransplantation with the Spectrum of Transplantion

DTIC Science & Technology

2015-10-01

therapeutic option for patients in need of advanced tissue reconstruction. II. Keywords Biorepository, vascularized composite allograft , nonhuman primates... tissues (e.g. hand, face) into a useful therapeutic option for individuals in need of advance tissue reconstruction and replacement. The proposal...death but increased the rate of soft tissue injury. Vascularized composite allotransplantation (VCA) has recently emerged as a promising strategy for

A clade in the QUASIMODO2 family evolved with vascular plants and supports a role for cell wall composition in adaptation to environmental changes.

PubMed

Fuentes, Sara; Pires, Nuno; Østergaard, Lars

2010-08-01

The evolution of plant vascular tissue is tightly linked to the evolution of specialised cell walls. Mutations in the QUASIMODO2 (QUA2) gene from Arabidopsis thaliana were previously shown to result in cell adhesion defects due to reduced levels of the cell wall component homogalacturonic acid. In this study, we provide additional information about the role of QUA2 and its closest paralogues, QUASIMODO2 LIKE1 (QUL1) and QUL2. Within the extensive QUA2 family, our phylogenetic analysis shows that these three genes form a clade that evolved with vascular plants. Consistent with a possible role of this clade in vasculature development, QUA2 is highly expressed in the vascular tissue of embryos and inflorescence stems and overexpression of QUA2 resulted in temperature-sensitive xylem collapse. Moreover, in-depth characterisation of qua2 qul1 qul2 triple mutant and 35S::QUA2 overexpression plants revealed contrasting temperature-dependent stem development with dramatic effects on stem width. Taken together, our results suggest that the QUA2-specific clade contributed to the evolution of vasculature and illustrate the important role that modification of cell wall composition plays in the adaptation to changing environmental conditions, including changes in temperature.

Gas gangrene (image)

MedlinePlus

Gas gangrene is a severe form of gangrene (tissue death) caused by the bacterium Clostridium perfringens. Patients with ... vascular diseases are more prone to spontaneously develop gas gangrene, which is rapidly progressive and often fatal.

Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

PubMed

Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

2018-02-01

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

The impact of various scaffold components on vascularized bone constructs.

PubMed

Eweida, Ahmad; Schulte, Matthias; Frisch, Oliver; Kneser, Ulrich; Harhaus, Leila

2017-06-01

Bone tissue engineering is gaining more interest in the field of craniofacial surgery where continuous efforts are being made to improve the outcomes via modulation of the scaffold components. In an in vitro three dimensional (3D) culture, the effect of bone morphogenic protein 2 (BMP2, 60 μg/ml) and the effect of different cell seeding densities (0.25, 0.5, and 1 × 104) of rat mesenchymal stem cells seeded on nanocrystalline hydroxyapatite in silica gel matrix (Nanobone ® ) on the cell viability and differentiation were studied. Alkaline phosphatase and viability assays were performed at day 7, day 14, and day 21 to assess the differentiation and the relative fraction of viable cells in the 3D cell cultures. In a subsequent in vivo study, we examined the effect of axial vascularization, the scaffold's particle size and the nature of the matrix (collagen type I vs. diluted fibrin) on vascularization and tissue generation in vascularized bone construct in rats. Regarding vascularization, we compared constructs vascularized randomly by extrinsic vascularization from the periphery of the implanted construct with others vascularized axially via an implanted arteriovenous loop (AVL). Regarding the particle size, we compared constructs having a scaffold particle size of 0.2 mm (powder) with other constructs having a particle size of 2 × 0.6 mm (granules). Regarding the matrix we compared constructs having a collagen matrix with others having a fibrin matrix. Various groups were compared regarding the amount of tissue generation, vascularization, and cellular proliferation. The initial seeding density had a temporary and minimal effect on the overall osteogenic differentiation of the cells. On the contrary, adding BMP2 in a concentration of 60 μg/ml over one week led to an overall enhanced osteogenic differentiation despite depressed cell viability. Axial vascularization was mandatory for efficient tissue formation and vascularization of the bone construct. Collagen matrix and a smaller particle size provided more favorable results in terms of vascularization and tissue formation than diluted fibrin and larger Nanobone particles. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Bioengineered vascular scaffolds: the state of the art.

PubMed

Palumbo, Vincenzo D; Bruno, Antonio; Tomasello, Giovanni; Damiano, Giuseppe; Lo Monte, Attilio I

2014-07-31

To date, there is increasing clinical need for vascular substitutes due to accidents, malformations, and ischemic diseases. Over the years, many approaches have been developed to solve this problem, starting from autologous native vessels to artificial vascular grafts; unfortunately, none of these have provided the perfect vascular substitute. All have been burdened by various complications, including infection, thrombogenicity, calcification, foreign body reaction, lack of growth potential, late stenosis and occlusion from intimal hyperplasia, and pseudoaneurysm formation. In the last few years, vascular tissue engineering has emerged as one of the most promising approaches for producing mechanically competent vascular substitutes. Nanotechnologies have contributed their part, allowing extraordinarily biostable and biocompatible materials to be developed. Specifically, the use of electrospinning to manufacture conduits able to guarantee a stable flow of biological fluids and guide the formation of a new vessel has revolutionized the concept of the vascular substitute. The electrospinning technique allows extracellular matrix (ECM) to be mimicked with high fidelity, reproducing its porosity and complexity, and providing an environment suitable for cell growth. In the future, a better knowledge of ECM and the manufacture of new materials will allow us to "create" functional biological vessels - the base required to develop organ substitutes and eventually solve the problem of organ failure.

A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts

PubMed Central

Hibino, Narutoshi; Yi, Tai; Duncan, Daniel R.; Rathore, Animesh; Dean, Ethan; Naito, Yuji; Dardik, Alan; Kyriakides, Themis; Madri, Joseph; Pober, Jordan S.; Shinoka, Toshiharu; Breuer, Christopher K.

2011-01-01

The primary graft-related complication during the first clinical trial evaluating the use of tissue-engineered vascular grafts (TEVGs) was stenosis. We investigated the role of macrophages in the formation of TEVG stenosis in a murine model. We analyzed the natural history of TEVG macrophage infiltration at critical time points and evaluated the role of cell seeding on neovessel formation. To assess the function of infiltrating macrophages, we implanted TEVGs into mice that had been macrophage depleted using clodronate liposomes. To confirm this, we used a CD11b-diphtheria toxin-receptor (DTR) transgenic mouse model. Monocytes infiltrated the scaffold within the first few days and initially transformed into M1 macrophages. As the scaffold degraded, the macrophage infiltrate disappeared. Cell seeding decreased the incidence of stenosis (32% seeded, 64% unseeded, P=0.024) and the degree of macrophage infiltration at 2 wk. Unseeded TEVGs demonstrated conversion from M1 to M2 phenotype, whereas seeded grafts did not. Clodronate and DTR inhibited macrophage infiltration and decreased stenosis but blocked formation of vascular neotissue, evidenced by the absence of endothelial and smooth muscle cells and collagen. These findings suggest that macrophage infiltration is critical for neovessel formation and provides a strategy for predicting, detecting, and inhibiting stenosis in TEVGs.—Hibino, N., Yi, T., Duncan, D. R., Rathore, A., Dean, E., Naito, Y., Dardik, A., Kyriakides, T., Madri, J., Pober, J. S., Shinoka, T., Breuer, C. K. A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts. PMID:21865316

Development of In Vitro Embryo Production System Using Collagen Matrix Gel Attached with Vascular Endothelial Growth Factor Derived from Interleukin-1 Beta-Treated Porcine Endometrial Tissue.

PubMed

Han, Hye-In; Lee, Sang-Hee; Park, Choon-Keun

2017-07-01

The aim of this study was to establish an embryo culture system using collagen gel attached with vascular endothelial growth factor (VEGF) derived from interleukin-1 beta (IL-1β)-treated endometrial tissues from pigs. Endometria were separated from the porcine uterus at the follicular phase of the estrous cycle and were cultured with IL-1β. The collagen gels coincubated with IL-1β-treated endometria (C, without endometrial tissue; CE, with endometrial tissue; and CEI, IL-1β-treated endometrial tissue) were used for embryo culture. We found that, compared with the comparable figures in the control group, prostaglandin synthase-2 (PTGS-2) mRNA was increased in IL-1β-treated endometrial tissue (p < 0.05). The VEGF protein was not observed in collagen gel coincubated without endometrial tissue (C); however, it was detected in collagen gels coincubated with endometrial tissue (CE and CEI). The embryo cleavage rates and blastocyst formation did not differ among the treatment groups. The proportion of blastocysts did not differ among the groups. However, the number of blastocyst cells was significantly (p < 0.05) higher in the CEI group than in the other groups. These results clarify the effects of the intrauterine environment on preimplantation embryos and may be useful in research on the effects of extracellular matrix- and cytokine-treated endometrial tissue on embryo development.

Microvascular responsiveness in obesity: implications for therapeutic intervention

PubMed Central

Bagi, Zsolt; Feher, Attila; Cassuto, James

2012-01-01

Obesity has detrimental effects on the microcirculation. Functional changes in microvascular responsiveness may increase the risk of developing cardiovascular complications in obese patients. Emerging evidence indicates that selective therapeutic targeting of the microvessels may prevent life-threatening obesity-related vascular complications, such as ischaemic heart disease, heart failure and hypertension. It is also plausible that alterations in adipose tissue microcirculation contribute to the development of obesity. Therefore, targeting adipose tissue arterioles could represent a novel approach to reducing obesity. This review aims to examine recent studies that have been focused on vasomotor dysfunction of resistance arteries in obese humans and animal models of obesity. Particularly, findings in coronary resistance arteries are contrasted to those obtained in other vascular beds. We provide examples of therapeutic attempts, such as use of statins, ACE inhibitors and insulin sensitizers to prevent obesity-related microvascular complications. We further identify some of the important challenges and opportunities going forward. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21797844

Reconstruction of Extensive Soft-Tissue Defects with Concomitant Bone Defects in the Lower Extremity with the Latissimus Dorsi-Serratus Anterior-Rib Free Flap.

PubMed

Sia, Wei Tee; Xu, Germaine Guiqin; Puhaindran, Mark Edward; Tan, Bien Keem; Cheng, Mathew Hern Wang; Chew, Winston Yoon Chong

2015-07-01

The combined latissimus dorsi-serratus anterior-rib (LD-SA-rib) free flap provides a large soft-tissue flap with a vascularized bone flap through a solitary vascular pedicle in a one-stage reconstruction. Seven LD-SA-rib free flaps were performed in seven patients to reconstruct concomitant bone and extensive soft-tissue defects in the lower extremity (tibia, five; femur, one; foot, one). The patients were all male, with an average age of 34 years (range, 20-48 years). These defects were secondary to trauma in five patients and posttraumatic osteomyelitis in two patients. All flaps survived and achieved bony union. The average time to bony union was 9.4 months. Bone hypertrophy of at least 20% occurred in all flaps. All patients achieved full weight-bearing ambulation without aid at an average duration of 23.7 months. Two patients developed stress fractures of the rib flap. There was no significant donor site morbidity, except for two patients who had pleural tears during harvesting of the flap. The LD-SA-rib flap provides a large soft-tissue component and a vascularized bone flap for reconstruction of composite large soft-tissue defects with concomitant bone defects of the lower extremity in a one-stage procedure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Modeling of heat transfer in a vascular tissue-like medium during an interstitial hyperthermia process.

PubMed

Hassanpour, Saeid; Saboonchi, Ahmad

2016-12-01

This paper aims to evaluate the role of small vessels in heat transfer mechanisms of a tissue-like medium during local intensive heating processes, for example, an interstitial hyperthermia treatment. To this purpose, a cylindrical tissue with two co- and counter-current vascular networks and a central heat source is introduced. Next, the energy equations of tissue, supply fluid (arterial blood), and return fluid (venous blood) are derived using porous media approach. Then, a 2D computer code is developed to predict the temperature of blood (fluid phase) and tissue (solid phase) by conventional volume averaging method and a more realistic solution method. In latter method, despite the volume averaging the blood of interconnect capillaries is separated from the arterial and venous blood phases. It is found that in addition to blood perfusion rate, the arrangement of vascular network has considerable effects on the pattern and amount of the achieved temperature. In contrast to counter-current network, the co-current network of vessels leads to considerable asymmetric pattern of temperature contours and relocation of heat affected zone along the blood flow direction. However this relocation can be prevented by changing the site of hyperthermia heat source. The results show that the cooling effect of co-current blood vessels during of interstitial heating is more efficient. Despite much anatomical dissimilarities, these findings can be useful in designing of protocols for hyperthermia cancer treatment of living tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine.

PubMed

Bukovsky, Antonin; Caudle, Michael R; Carson, Ray J; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M

2009-02-13

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.

Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine

PubMed Central

Bukovsky, Antonin; Caudle, Michael R.; Carson, Ray J.; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M.

2009-01-01

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders. PMID:20195382

An anisotropically and heterogeneously aligned patterned electrospun scaffold with tailored mechanical property and improved bioactivity for vascular tissue engineering.

PubMed

Xu, He; Li, Haiyan; Ke, Qinfei; Chang, Jiang

2015-04-29

The development of vascular scaffolds with controlled mechanical properties and stimulatory effects on biological activities of endothelial cells still remains a significant challenge to vascular tissue engineering. In this work, we reported an innovative approach to prepare a new type of vascular scaffolds with anisotropically and heterogeneously aligned patterns using electrospinning technique with unique wire spring templates, and further investigated the structural effects of the patterned electrospun scaffolds on mechanical properties and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs). Results showed that anisotropically aligned patterned nanofibrous structure was obtained by depositing nanofibers on template in a structurally different manner, one part of nanofibers densely deposited on the embossments of wire spring and formed cylindrical-like structures in the transverse direction, while others loosely suspended and aligned along the longitudinal direction, forming a three-dimensional porous microstructure. We further found that such structures could efficiently control the mechanical properties of electrospun vascular scaffolds in both longitudinal and transverse directions by altering the interval distances between the embossments of patterned scaffolds. When HUVECs were cultured on scaffolds with different microstructures, the patterned scaffolds distinctively promoted adhesion of HUVECs at early stage and proliferation during the culture period. Most importantly, cells experienced a large shape change associated with cell cytoskeleton and nuclei remodeling, leading to a stimulatory effect on angiogenesis differentiation of HUVECs by the patterned microstructures of electrospun scaffolds, and the scaffolds with larger distances of intervals showed a higher stimulatory effect. These results suggest that electrospun scaffolds with the anisotropically and heterogeneously aligned patterns, which could efficiently control the mechanical properties and bioactivities of the scaffolds, might have great potential in vascular tissue engineering application.

Expanded polytetrafluoroethylene membrane alters tissue response to implanted Ahmed glaucoma valve.

PubMed

DeCroos, Francis Char; Ahmad, Sameer; Kondo, Yuji; Chow, Jessica; Mordes, Daniel; Lee, Maria Regina; Asrani, Sanjay; Allingham, R Rand; Olbrich, Kevin C; Klitzman, Bruce

2009-07-01

Long-term intraocular pressure control by glaucoma drainage implants is compromised by the formation of an avascular fibrous capsule that surrounds the glaucoma implant and increases aqueous outflow resistance. It is possible to alter this fibrotic tissue reaction and produce a more vascularized and potentially more permeable capsule around implanted devices by enclosing them in a porous membrane. Ahmed glaucoma implants modified with an outer 5-microm pore size membrane (termed porous retrofitted implant with modified enclosure or PRIME-Ahmed) and unmodified glaucoma implants were implanted into paired rabbit eyes. After 6 weeks, the devices were explanted and subject to histological analysis. A tissue response containing minimal vascularization, negligible immune response, and a thick fibrous capsule surrounded the unmodified Ahmed glaucoma implant. In comparison, the tissue response around the PRIME-Ahmed demonstrated a thinner fibrous capsule (46.4 +/- 10.8 microm for PRIME-Ahmed versus 94.9 +/- 21.2 microm for control, p < 0.001) and was highly vascularized near the tissue-material interface. A prominent chronic inflammatory response was noted as well. Encapsulating the aqueous outflow pathway with a porous membrane produces a more vascular tissue response and thinner fibrous capsule compared with a standard glaucoma implant plate. Enhanced vascularity and a thinner fibrous capsule may reduce aqueous outflow resistance and improve long-term glaucoma implant performance.

Vascular rarefaction mediates whitening of brown fat in obesity

PubMed Central

Shimizu, Ippei; Aprahamian, Tamar; Kikuchi, Ryosuke; Shimizu, Ayako; Papanicolaou, Kyriakos N.; MacLauchlan, Susan; Maruyama, Sonomi; Walsh, Kenneth

2014-01-01

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism. PMID:24713652

Engineering Complex Tissues

PubMed Central

MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

2010-01-01

This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue regeneration, and discussed new biomaterials that can be used to develop new regenerative technologies. PMID:17518671

Effects of Anti-VEGF on Predicted Antibody Biodistribution: Roles of Vascular Volume, Interstitial Volume, and Blood Flow

PubMed Central

Boswell, C. Andrew; Ferl, Gregory Z.; Mundo, Eduardo E.; Bumbaca, Daniela; Schweiger, Michelle G.; Theil, Frank-Peter; Fielder, Paul J.; Khawli, Leslie A.

2011-01-01

Background The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. Methodology/Principal Findings Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. Conclusions/Significance These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF. PMID:21436893

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

Hydrogels for Engineering of Perfusable Vascular Networks

PubMed Central

Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

2015-01-01

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

Guidance of vascular development: lessons from the nervous system.

PubMed

Larrivée, Bruno; Freitas, Catarina; Suchting, Steven; Brunet, Isabelle; Eichmann, Anne

2009-02-27

The vascular system of vertebrates consists of an organized, branched network of arteries, veins, and capillaries that penetrates all the tissues of the body. One of the most striking features of the vascular system is that its branching pattern is highly stereotyped, with major and secondary branches forming at specific sites and developing highly conserved organ-specific vascular patterns. The factors controlling vascular patterning are not yet completely understood. Recent studies have highlighted the anatomic and structural similarities between blood vessels and nerves. The 2 networks are often aligned, with nerve fibers and blood vessels following parallel routes. Furthermore, both systems require precise control over their guidance and growth. Several molecules with attractive and repulsive properties have been found to modulate the proper guidance of both nerves and blood vessels. These include the Semaphorins, the Slits, and the Netrins and their receptors. In this review, we describe the molecular mechanisms by which blood vessels and axons achieve proper path finding and the molecular cues that are involved in their guidance.

Optical Microangiography Based on Optical Coherence Tomography

NASA Astrophysics Data System (ADS)

Reif, Roberto; Wang, Ruikang K.

Proper homeostasis regulation of in vivo biological systems requires microvascular blood perfusion, which is the process of delivering blood into the tissue's capillary beds. Abnormal tissue vascularization has been associated with various diseases such as cancer, diabetes, neurological disorders, wounds, and inflammation. Understanding the changes in the vascular network or microangiography will have an important role in determining the causes and developing potential treatments for these diseases. Optical coherence tomography (OCT) is a noninvasive method for imaging three-dimensional biological tissues with high resolution (~10 µm) and without requiring the use of contrast agents. In this chapter we review several techniques for using OCT to determine blood flow velocities and the vessel morphology (optical microangiography). Different techniques will be discussed with a brief explanation of their limitations. Also, methods for quantifying these images are presented, as well as the depiction of several applications.

Predicting the size-dependent tissue accumulation of agents released from vascular targeted nanoconstructs

NASA Astrophysics Data System (ADS)

de Tullio, Marco D.; Singh, Jaykrishna; Pascazio, Giuseppe; Decuzzi, Paolo

2014-03-01

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vessel wall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate , ranging from to ; the wall filtration velocity , varying from to ; and the agent diffusion coefficient , ranging from to . It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate , and with a decrease in filtration velocity and agent diffusivity . In particular, in tumor microvessels, characterized by lower shear rates () and higher filtration velocities (), an agent with a diffusivity (i.e. a 50 nm particle) is predicted to deposit on the vessel wall up to of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (), are predicted to accumulate up to . In healthy vessels, characterized by higher and lower , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.

Mapping the vascular anatomy of free transplanted soft tissue flaps with computed tomographic angiography.

PubMed

Rozen, Warren M; Chubb, Daniel; Ashton, Mark W; Webster, Howard R

2012-05-01

The use of advanced imaging technologies such as computed tomographic angiography (CTA) has opened the door to the analysis of microvascular anatomy not previously demonstrable with prior imaging techniques. While CTA has been used to evaluate the vascular anatomy of donor body regions in the planning of harvest of tissue for free flap transfer, the use of CTA to evaluate tissues after tissue transplantation has not been demonstrated. The current study aimed to explore whether vascular anatomy was able to highlight CTA within transferred flaps. The arterial and venous anatomy of a transferred deep inferior epigastric artery (DIEA) perforator (DIEP) flap was explored postoperatively with the use of CTA. Intra-flap vasculature was mapped and recorded qualitatively. Postoperative CTA is able to highlight the vascular pedicle of a transferred free flap, highlight the course of individual perforators supplying the flap, and map the zones of lesser perfusion by the source pedicle. The current study has demonstrated that CTA may be of value in identifying vascular anatomy within transferred tissue, as a guide to evaluate flap perfusion and planning further surgery involving the flap. © Springer-Verlag 2011

Triactome: Neuro–Immune–Adipose Interactions. Implication in Vascular Biology

PubMed Central

Chaldakov, George Nikov; Fiore, Marco; Ghenev, Peter I.; Beltowski, Jerzy; Ranćić, Gorana; Tunçel, Neşe; Aloe, Luigi

2014-01-01

Understanding how the precise interactions of nerves, immune cells, and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy, and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. PAAT expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic) signaling proteins collectively dubbed adipokines. However, the role of vascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro–immune–adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease. PMID:24782857

Regenerative medicine as applied to solid organ transplantation: current status and future challenges

PubMed Central

Orlando, Giuseppe; Baptista, Pedro; Birchall, Martin; De Coppi, Paolo; Farney, Alan; Guimaraes-Souza, Nadia K.; Opara, Emmanuel; Rogers, Jeffrey; Seliktar, Dror; Shapira-Schweitzer, Keren; Stratta, Robert J.; Atala, Anthony; Wood, Kathryn J.; Soker, Shay

2013-01-01

Summary In the last two decades, regenerative medicine has shown the potential for “bench-to-bedside” translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using “natural tissue” scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immuno-suppression. This review describes recent advances in the engineering of several key tissues and organs. PMID:21062367

Triactome: neuro-immune-adipose interactions. Implication in vascular biology.

PubMed

Chaldakov, George Nikov; Fiore, Marco; Ghenev, Peter I; Beltowski, Jerzy; Ranćić, Gorana; Tunçel, Neşe; Aloe, Luigi

2014-01-01

Understanding how the precise interactions of nerves, immune cells, and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy, and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. PAAT expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic) signaling proteins collectively dubbed adipokines. However, the role of vascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue.

PubMed

Byambaa, Batzaya; Annabi, Nasim; Yue, Kan; Trujillo-de Santiago, Grissel; Alvarez, Mario Moisés; Jia, Weitao; Kazemzadeh-Narbat, Mehdi; Shin, Su Ryon; Tamayol, Ali; Khademhosseini, Ali

2017-08-01

Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMA LOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels.

PubMed

Wang, Xiaolin; Phan, Duc T T; Sobrino, Agua; George, Steven C; Hughes, Christopher C W; Lee, Abraham P

2016-01-21

This paper reports a method for generating an intact and perfusable microvascular network that connects to microfluidic channels without appreciable leakage. This platform incorporates different stages of vascular development including vasculogenesis, endothelial cell (EC) lining, sprouting angiogenesis, and anastomosis in sequential order. After formation of a capillary network inside the tissue chamber via vasculogenesis, the adjacent microfluidic channels are lined with a monolayer of ECs, which then serve as the high-pressure input ("artery") and low pressure output ("vein") conduits. To promote a tight interconnection between the artery/vein and the capillary network, sprouting angiogenesis is induced, which promotes anastomosis of the vasculature inside the tissue chamber with the EC lining along the microfluidic channels. Flow of fluorescent microparticles confirms the perfusability of the lumenized microvascular network, and minimal leakage of 70 kDa FITC-dextran confirms physiologic tightness of the EC junctions and completeness of the interconnections between artery/vein and the capillary network. This versatile device design and its robust construction methodology establish a physiological transport model of interconnected perfused vessels from artery to vascularized tissue to vein. The system has utility in a wide range of organ-on-a-chip applications as it enables the physiological vascular interconnection of multiple on-chip tissue constructs that can serve as disease models for drug screening.

In Vitro Endothelialization of Biodegradable Vascular Grafts Via Endothelial Progenitor Cell Seeding and Maturation in a Tubular Perfusion System Bioreactor.

PubMed

Melchiorri, Anthony J; Bracaglia, Laura G; Kimerer, Lucas K; Hibino, Narutoshi; Fisher, John P

2016-07-01

A critical challenge to the success of biodegradable vascular grafts is the establishment of a healthy endothelium. To establish this monolayer of endothelial cells (ECs), a variety of techniques have been developed, including cell seeding. Vascular grafts may be seeded with relevant cell types and allowed to mature before implantation. Due to the low proliferative ability of adult ECs and issues with donor site morbidity, there has been increasing interest in using endothelial progenitor cells (EPCs) for vascular healing procedures. In this work, we combined the proliferative and differentiation capabilities of a commercial cell line of early EPCs with an established bioreactor system to support the maturation of cell-seeded vascular grafts. All components of the vascular graft and bioreactor setup are commercially available and allow for complete customization of the scaffold and culturing system. This bioreactor setup enables the control of flow through the graft, imparting fluid shear stress on EPCs and affecting cellular proliferation and differentiation. Grafts cultured with EPCs in the bioreactor system demonstrated greatly increased cell populations and neotissue formation compared with grafts seeded and cultured in a static system. Increased expression of markers for mature endothelial tissues were also observed in bioreactor-cultured EPC-seeded grafts. These findings suggest the distinct advantages of a customizable bioreactor setup for the proliferation and maturation of EPCs. Such a strategy may be beneficial for utilizing EPCs in vascular tissue engineering applications.

Toward a patient-specific tissue engineered vascular graft

PubMed Central

Best, Cameron; Strouse, Robert; Hor, Kan; Pepper, Victoria; Tipton, Amy; Kelly, John; Shinoka, Toshiharu; Breuer, Christopher

2018-01-01

Integrating three-dimensional printing with the creation of tissue-engineered vascular grafts could provide a readily available, patient-specific, autologous tissue source that could significantly improve outcomes in newborns with congenital heart disease. Here, we present the recent case of a candidate for our tissue-engineered vascular graft clinical trial deemed ineligible due to complex anatomical requirements and consider the application of three-dimensional printing technologies for a patient-specific graft. We 3D-printed a closed-disposable seeding device and validated that it performed equivalently to the traditional open seeding technique using ovine bone marrow–derived mononuclear cells. Next, our candidate’s preoperative imaging was reviewed to propose a patient-specific graft. A seeding apparatus was then designed to accommodate the custom graft and 3D-printed on a commodity fused deposition modeler. This exploratory feasibility study represents an important proof of concept advancing progress toward a rationally designed patient-specific tissue-engineered vascular graft for clinical application. PMID:29568478

[Possibilities and prospects of three-dimensional bioprinting in vascular surgery].

PubMed

Gavrilenko, A V; Khesuani, Yu J; Kalinin, V D

2016-01-01

Rapid development of tissue engineering is gradually changing the approach to patient care. Despite the fact that the use of an autograft or transplantation of an artificial prosthesis is preferred in most cases, this is frequently impossible due to shortage of suitable material or the patient's condition. Regenerative medicine and tissue engineering make it possible to reduce the terms of treatment and restoration after vascular operations, as well as complications rate. At the present moment there is a lot of information about methods of biofabrication and multiple techniques of using stem cells. Nevertheless, clinical efficacy of these methods requires further detailed examination. The review of literature contains the data concerning modern achievements in the area of bioprinting.

Cellular responses to endogenous electrochemical gradients in morphological development

NASA Technical Reports Server (NTRS)

Desrosiers, M. F.

1996-01-01

Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: (1) intercellular organization and development through their effects on the membrane potential, (2) direct effects such as electrophoresis of membrane components, and (3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: (1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, (2) the ionic conductance changes within seconds showing altered transport between the tissues, and (3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

PubMed Central

Nicolosi, Pier Andrea; Tombetti, Enrico; Maugeri, Norma; Rovere-Querini, Patrizia; Brunelli, Silvia; Manfredi, Angelo A.

2016-01-01

Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment. PMID:27069480

Development, characterisation and biocompatibility testing of a cobalt-containing titanium phosphate-based glass for engineering of vascularized hard tissues.

PubMed

Lee, In-Ho; Yu, Hye-sun; Lakhkar, Nilay J; Kim, Hae-Won; Gong, Myoung-Seon; Knowles, Jonathan C; Wall, Ivan B

2013-05-01

There is a continuing need to develop scaffold materials that can promote vascularisation throughout the tissue engineered construct. This study investigated the effect of cobalt oxide (CoO) doped into titanium phosphate glasses on material properties, biocompatibility and vascular endothelial growth factor (VEGF) secretion by osteoblastic MG63 cells. Glasses composed of (P2O5)45(Na2O)20(TiO2)05(CaO)30-x(CoO)x(x=0, 5, 10, and 15 mol%) were fabricated and the effect of Co on physicochemical properties including density, glass transition temperature (Tg), degradation rate, ion release, and pH changes was assessed. The results showed that incorporation of CoO into the glass system produced an increase in density with little change in Tg. It was then confirmed that the pH did not change significantly when CoO was incorporated in the glass, and stayed constant at around 6.5-7.0 throughout the dissolution study period of 336 h. Ion release results followed a specific pattern with increasing amounts of CoO. In general, although incorporation of CoO into a titanium phosphate glass increased its density, other bulk and surface properties of the glass did not show any significant changes. Cell culture studies performed using MG63 cells over a 7-day period indicated that the glasses provide a stable surface for cell attachment and are biocompatible. Furthermore, VEGF secretion was significantly enhanced on all glasses compared with standard tissue culture plastic and Co doping enhanced this effect further. In conclusion, the developed Co-doped glasses are stable and biocompatible and thus offer enhanced potential for engineering vascularized tissue. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Challenges in Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P.; Radisic, Milica

2010-01-01

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell—the actual “tissue engineer”—is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure. PMID:19698068

Thermal inkjet printing in tissue engineering and regenerative medicine.

PubMed

Cui, Xiaofeng; Boland, Thomas; D'Lima, Darryl D; Lotz, Martin K

2012-08-01

With the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the desired 2D and 3D locations, bioprinting has great potential to develop promising approaches in translational medicine and organ replacement. The most recent advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review. Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction. With layer-by-layer assembly, 3D tissues with complex structures can be printed using scanned CT or MRI images. Vascular or nerve systems can be enabled simultaneously during the organ construction with digital control. Therefore, bioprinting is the only solution to solve this critical issue in thick and complex tissues fabrication with vascular system. Collectively, bioprinting based on thermal inkjet has great potential and broad applications in tissue engineering and regenerative medicine. This review article introduces some important patents related to bioprinting of living systems and the applications of bioprinting in tissue engineering field.

Creation of a Bioengineered Skin Flap Scaffold with a Perfusable Vascular Pedicle.

PubMed

Jank, Bernhard J; Goverman, Jeremy; Guyette, Jacques P; Charest, Jon M; Randolph, Mark; Gaudette, Glenn R; Gershlak, Joshua R; Purschke, Martin; Javorsky, Emilia; Nazarian, Rosalynn M; Leonard, David A; Cetrulo, Curtis L; Austen, William G; Ott, Harald C

2017-07-01

Full-thickness skin loss is a challenging problem due to limited reconstructive options, demanding 75 million surgical procedures annually in the United States. Autologous skin grafting is the gold standard treatment, but results in donor-site morbidity and poor aesthetics. Numerous skin substitutes are available on the market to date, however, none truly functions as full-thickness skin due to lack of a vascular network. The creation of an autologous full-thickness skin analogue with a vascular pedicle would result in a paradigm shift in the management of wounds and in reconstruction of full-thickness skin defects. To create a clinically relevant foundation, we generated an acellular skin flap scaffold (SFS) with a perfusable vascular pedicle of clinically relevant size by perfusion decellularization of porcine fasciocutaneous flaps. We then analyzed the yielded SFS for mechanical properties, biocompatibility, and regenerative potential in vitro and in vivo. Furthermore, we assessed the immunological response using an in vivo model. Finally, we recellularized the vascular compartment of an SFS and reconnected it to a recipient's blood supply to test for perfusability. Perfusion decellularization removed all cellular components with preservation of native extracellular matrix composition and architecture. Biaxial testing revealed preserved mechanical properties. Immunologic response and biocompatibility assessed via implantation and compared with native xenogenic skin and commercially available dermal substitutes revealed rapid neovascularization and complete tissue integration. Composition of infiltrating immune cells showed no evidence of allorejection and resembled the inflammatory phase of wound healing. Implantation into full-thickness skin defects demonstrated good tissue integration and skin regeneration without cicatrization. We have developed a protocol for the generation of an SFS of clinically relevant size, containing a vascular pedicle, which can be utilized for perfusion decellularization and, ultimately, anastomosis to the recipient vascular system after precellularization. The observed favorable immunological response and good tissue integration indicate the substantial regenerative potential of this platform.

Adipose Tissue-Derived Pericytes for Cartilage Tissue Engineering.

PubMed

Zhang, Jinxin; Du, Chunyan; Guo, Weimin; Li, Pan; Liu, Shuyun; Yuan, Zhiguo; Yang, Jianhua; Sun, Xun; Yin, Heyong; Guo, Quanyi; Zhou, Chenfu

2017-01-01

Mesenchymal stem cells (MSCs) represent a promising alternative source for cartilage tissue engineering. However, MSC culture is labor-intensive, so these cells cannot be applied immediately to regenerate cartilage for clinical purposes. Risks during the ex vivo expansion of MSCs, such as infection and immunogenicity, can be a bottleneck in their use in clinical tissue engineering. As a novel stem cell source, pericytes are generally considered to be the origin of MSCs. Pericytes do not have to undergo time-consuming ex vivo expansion because they are uncultured cells. Adipose tissue is another optimal stem cell reservoir. Because adipose tissue is well vascularized, a considerable number of pericytes are located around blood vessels in this accessible and dispensable tissue, and autologous pericytes can be applied immediately for cartilage regeneration. Thus, we suggest that adipose tissue-derived pericytes are promising seed cells for cartilage regeneration. Many studies have been performed to develop isolation methods for the adipose tissuederived stromal vascular fraction (AT-SVF) using lipoaspiration and sorting pericytes from AT-SVF. These methods are useful for sorting a large number of viable pericytes for clinical therapy after being combined with automatic isolation using an SVF device and automatic magnetic-activated cell sorting. These tools should help to develop one-step surgery for repairing cartilage damage. However, the use of adipose tissue-derived pericytes as a cell source for cartilage tissue engineering has not drawn sufficient attention and preclinical studies are needed to improve cell purity, to increase sorting efficiency, and to assess safety issues of clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Populus Class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems

Treesearch

Marcel Robischon; Juan Du; Eriko Miura; Andrew Groover

2011-01-01

The secondary growth of a woody stem requires the formation of a vascular cambium at an appropriate position and proper patterning of the vascular tissues derived from the cambium. Class III homeodomain-leucine zipper (HD ZIP) transcription factors have been implicated in polarity determination and patterning in lateral organs and primary vascular tissues and in the...

Developmental pathway from leaves to galls induced by a sap-feeding insect on Schinus polygamus (Cav.) Cabrera (Anacardiaceae).

PubMed

Dias, Graciela G; Ferreira, Bruno G; Moreira, Gilson R P; Isaias, Rosy M S

2013-03-01

Galling sap-feeding insects are presumed to cause only minor changes in host plant tissues, because they usually do not require development of nutritive tissues for their own use. This premise was examined through comparison of the histometry, cytometry and anatomical development of non-galled leaves and galls of Calophya duvauae (Scott) (Hemiptera: Calophyidae) on Schinus polygamus (Cav.) Cabrera (Anacardiaceae). Cell fates changed from non-galled leaves to galls during the course of tissue differentiation. C. duvauae caused changes in dermal, ground, and vascular systems of the leaves of S. polygamus. Its feeding activity induced the homogenization of the parenchyma, and the neoformation of vascular bundles and trichomes. The histometric and cytometric data revealed compensatory effects of hyperplasia and cell hypertrophy in the epidermis, with hyperplasia predominating in the adaxial epidermis. There was a balance between these processes in the other tissues. Thus, we found major differences between the developmental pathways of non-galled leaves and galls. These changes were associated with phenotypic alterations related to shelter and appropriate microenvironmental conditions for the gall inducer. The nondifferentiation of a typical nutritive tissue in this case was compared to other non-phylogenetically related arthropod gall systems, and is suggested to result from convergence associated with the piercing feeding apparatus of the corresponding gall-inducer.

Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques

PubMed Central

Spadaccio, Cristiano; Nappi, Francesco; De Marco, Federico; Sedati, Pietro; Sutherland, Fraser W.H.; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto

2016-01-01

In this study, we tested in vivo effectiveness of a previously developed poly-l-lactide/poly-ε-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings. PMID:26949333

Aging, Atherosclerosis, and IGF-1

PubMed Central

Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

2012-01-01

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

Role of taurine in the vasculature: an overview of experimental and human studies

PubMed Central

Abebe, Worku; Mozaffari, Mahmood S

2011-01-01

Taurine is a sulfur-containing amino acid-like endogenous compound found in substantial amounts in mammalian tissues. It exerts a diverse array of biological effects, including cardiovascular regulation, antioxidation, modulation of ion transport, membrane stabilization, osmoregulation, modulation of neurotransmission, bile acid conjugation, hypolipidemia, antiplatelet activity and modulation of fetal development. This brief review summarizes the role of taurine in the vasculature and modulation of blood pressure, based on experimental and human studies. Oral supplementation of taurine induces antihypertensive effects in various animal models of hypertension. These effects of taurine have been shown to be both centrally and peripherally mediated. Consistent with this, taurine produces endothelium-dependent and independent relaxant effects in isolated vascular tissue preparations. Oral administration of taurine also ameliorates impairment of vascular reactivity, intimal thickening, arteriosclerosis, endothelial apoptosis, oxidative stress and inflammation, associated primarily with diabetes and, to a lesser extent with obesity, hypertension and nicotine-induced vascular adverse events. In rat aortic vascular smooth muscle cells (VSMCs), taurine acts as an antiproliferative and antioxidant agent. In endothelial cells, taurine inhibits apoptosis, inflammation, oxidative stress and cell death while increasing NO generation. Oral taurine in hypertensive human patients alleviates the symptoms of hypertension and also reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients. However, despite these favorable findings, there is a need to further establish certain aspects of the reported results and also consider addressing unresolved related issues. In addition, the molecular mechanism (s) involved in the vascular effects of taurine is largely unknown and requires further investigations. Elucidation of the mechanisms through which taurine affects the vasculature could facilitate the development of therapeutic and/or diet-based strategies to reduce the burdens of vascular diseases. PMID:22254206

Microfluidic Bioprinting for Engineering Vascularized Tissues and Organoids.

PubMed

Zhang, Yu Shrike; Pi, Qingmeng; van Genderen, Anne Metje

2017-08-11

Engineering vascularized tissue constructs and organoids has been historically challenging. Here we describe a novel method based on microfluidic bioprinting to generate a scaffold with multilayer interlacing hydrogel microfibers. To achieve smooth bioprinting, a core-sheath microfluidic printhead containing a composite bioink formulation extruded from the core flow and the crosslinking solution carried by the sheath flow, was designed and fitted onto the bioprinter. By blending gelatin methacryloyl (GelMA) with alginate, a polysaccharide that undergoes instantaneous ionic crosslinking in the presence of select divalent ions, followed by a secondary photocrosslinking of the GelMA component to achieve permanent stabilization, a microfibrous scaffold could be obtained using this bioprinting strategy. Importantly, the endothelial cells encapsulated inside the bioprinted microfibers can form the lumen-like structures resembling the vasculature over the course of culture for 16 days. The endothelialized microfibrous scaffold may be further used as a vascular bed to construct a vascularized tissue through subsequent seeding of the secondary cell type into the interstitial space of the microfibers. Microfluidic bioprinting provides a generalized strategy in convenient engineering of vascularized tissues at high fidelity.

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

PubMed Central

Miller, V.; Lin, A.; Kako, F.; Gabunia, K.; Kelemen, S.; Brettschneider, J.; Fridman, G.; Fridman, A.; Autieri, M.

2015-01-01

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue. PMID:26543345

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of themore » tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.« less

Telemedicine Can Replace the Neurologist on a Mobile Stroke Unit.

PubMed

Wu, Tzu-Ching; Parker, Stephanie A; Jagolino, Amanda; Yamal, Jose-Miguel; Bowry, Ritvij; Thomas, Abraham; Yu, Amy; Grotta, James C

2017-02-01

The BEST-MSU study (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit) is a comparative effectiveness trial in patients randomized to mobile stroke unit or standard management. A substudy tested interrater agreement for tissue-type plasminogen activator eligibility between a telemedicine vascular neurologist and onboard vascular neurologist. On scene, both the telemedicine vascular neurologist and onboard vascular neurologist independently evaluated the patient, documenting their tissue-type plasminogen activator treatment decision, National Institutes of Health Stroke Scale score, and computed tomographic interpretation. Agreement was determined using Cohen κ statistic. Telemedicine-related technical failures that impeded remote assessment were recorded. Simultaneous and independent telemedicine vascular neurologist and onboard vascular neurologist assessment was attempted in 174 patients. In 4 patients (2%), the telemedicine vascular neurologist could not make a decision because of technical problems. The telemedicine vascular neurologist agreed with the onboard vascular neurologist on 88% of evaluations (κ=0.73). Remote telemedicine vascular neurologist assessment is reliable and accurate, supporting either telemedicine vascular neurologist or onboard vascular neurologist assessment on our mobile stroke unit. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02190500. © 2017 American Heart Association, Inc.

Leaf hydraulics II: vascularized tissues.

PubMed

Rockwell, Fulton E; Holbrook, N Michele; Stroock, Abraham D

2014-01-07

Current models of leaf hydration employ an Ohm's law analogy of the leaf as an ideal capacitor, neglecting the resistance to flow between cells, or treat the leaf as a plane sheet with a source of water at fixed potential filling the mid-plane, neglecting the discrete placement of veins as well as their resistance. We develop a model of leaf hydration that considers the average conductance of the vascular network to a representative areole (region bounded by the vascular network), and represent the volume of tissue within the areole as a poroelastic composite of cells and air spaces. Solutions to the 3D flow problem are found by numerical simulation, and these results are then compared to 1D models with exact solutions for a range of leaf geometries, based on a survey of temperate woody plants. We then show that the hydration times given by these solutions are well approximated by a sum of the ideal capacitor and plane sheet times, representing the time for transport through the vasculature and tissue respectively. We then develop scaling factors relating this approximate solution to the 3D model, and examine the dependence of these scaling factors on leaf geometry. Finally, we apply a similar strategy to reduce the dimensions of the steady state problem, in the context of peristomatal transpiration, and consider the relation of transpirational gradients to equilibrium leaf water potential measurements. © 2013 Published by Elsevier Ltd. All rights reserved.

Framework of collagen type I - vasoactive vessels structuring invariant geometric attractor in cancer tissues: insight into biological magnetic field.

PubMed

Díaz, Jairo A; Murillo, Mauricio F; Jaramillo, Natalia A

2009-01-01

In a previous research, we have described and documented self-assembly of geometric triangular chiral hexagon crystal-like complex organizations (GTCHC) in human pathological tissues. This article documents and gathers insights into the magnetic field in cancer tissues and also how it generates an invariant functional geometric attractor constituted for collider partners in their entangled environment. The need to identify this hierarquic attractor was born out of the concern to understand how the vascular net of these complexes are organized, and to determine if the spiral vascular subpatterns observed adjacent to GTCHC complexes and their assembly are interrelational. The study focuses on cancer tissues and all the macroscopic and microscopic material in which GTCHC complexes are identified, which have been overlooked so far, and are rigorously revised. This revision follows the same parameters that were established in the initial phase of the investigation, but with a new item: the visualization and documentation of external dorsal serous vascular bed areas in spatial correlation with the localization of GTCHC complexes inside the tumors. Following the standard of the electro-optical collision model, we were able to reproduce and replicate collider patterns, that is, pairs of left and right hand spin-spiraled subpatterns, associated with the orientation of the spinning process that can be an expansion or contraction disposition of light particles. Agreement between this model and tumor data is surprisingly close; electromagnetic spiral patterns generated were identical at the spiral vascular arrangement in connection with GTCHC complexes in malignant tumors. These findings suggest that the framework of collagen type 1 - vasoactive vessels that structure geometric attractors in cancer tissues with invariant morphology sets generate collider partners in their magnetic domain with opposite biological behavior. If these principles are incorporated into nanomaterial, biomedical devices, and engineered tissues, new therapeutic strategies could be developed for cancer treatment.

76 FR 78216 - Organ Procurement and Transplantation Network

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... composite tissue allograft; however, for the purposes of rulemaking, the Health Resources and Services..., Hand transplantation and vascularized composite tissue allografts in orthopaedics and traumatology... vascularized composite allografts, described below, within the definition of organs covered by the rules...

Three-dimensional bioprinting of thick vascularized tissues

NASA Astrophysics Data System (ADS)

Kolesky, David B.; Homan, Kimberly A.; Skylar-Scott, Mark A.; Lewis, Jennifer A.

2016-03-01

The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.

Micro- and nanotechnology in cardiovascular tissue engineering.

PubMed

Zhang, Boyang; Xiao, Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

2011-12-09

While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

A Cost-Effective Culture System for the In Vitro Assembly, Maturation, and Stimulation of Advanced Multilayered Multiculture Tubular Tissue Models.

PubMed

Loy, Caroline; Pezzoli, Daniele; Candiani, Gabriele; Mantovani, Diego

2018-01-01

The development of tubular engineered tissues is a challenging research area aiming to provide tissue substitutes but also in vitro models to test drugs, medical devices, and even to study physiological and pathological processes. In this work, the design, fabrication, and validation of an original cost-effective tubular multilayered-tissue culture system (TMCS) are reported. By exploiting cellularized collagen gel as scaffold, a simple moulding technique and an endothelialization step on a rotating system, TMCS allowed to easily prepare in 48 h, trilayered arterial wall models with finely organized cellular composition and to mature them for 2 weeks without any need of manipulation. Multilayered constructs incorporating different combinations of vascular cells are compared in terms of cell organization and viscoelastic mechanical properties demonstrating that cells always progressively aligned parallel to the longitudinal direction. Also, fibroblast compacted less the collagen matrix and appeared crucial in term of maturation/deposition of elastic extracellular matrix. Preliminary studies under shear stress stimulation upon connection with a flow bioreactor are successfully conducted without damaging the endothelial monolayer. Altogether, the TMCS herein developed, thanks to its versatility and multiple functionalities, holds great promise for vascular tissue engineering applications, but also for other tubular tissues such as trachea or oesophagus. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Expression of vascular endothelial growth factor and its significance in pulmonary bronchoalveolar carcinoma].

PubMed

Song, Weian; Li, Hui; Wang, Huasheng; Zhang, Weidong; Zhao, Xiaogang

2004-02-20

To study the relationship between the vascular endothelial growth factor (VEGF) and the clinicopathological characteristics of the patients with pulmonary bronchoalveolar carcinoma, and to research the possible role of VEGF in the malignant growth of pulmonary bronchoalveolar carcinoma. The expression of VEGF and MVD were detected in 38 pulmonary bronchoalveolar carcinoma and 20 normal lung tissues by immunohistochemical method. The positive rate of VEGF expression (73.68%,28/38) and MVD (63.81±19.26) in pulmonary bronchoalveolar carcinoma tissues were both remarkably higher than those in normal lung tissues (0, 18.44±6.53)( P < 0.005,P < 0.001). The positive rate of VEGF expression was significantly related to the size of tumor ( P < 0.05), lymphatic metastasis ( P < 0.025) and TNM stage ( P < 0.05), and so did the MVD ( P < 0.05, P < 0.05, P < 0.05). MVD was remarkably higher in VEGF (+) carcinoma tissues than that in VEGF (-) carcinoma tissues ( P < 0.05). VEGF correlates with the clinicopathological characteristics of pulmonary bronchoalveolar carcinoma. It may play an important role in the development of pulmonary bronchoalveolar carcinoma.

The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

2013-01-01

The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform distribution of oxygen, solid tumor pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the interstitial fluid. PMID:23220211

High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

PubMed Central

Ager, Ann

2017-01-01

The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and control the function of lymphoid organs. PMID:28217126

Lymph microvascularization as a prognostic indicator in neuroblastoma.

PubMed

Tadeo, Irene; Gamero-Sandemetrio, Esther; Berbegall, Ana P; Gironella, Marta; Ritort, Félix; Cañete, Adela; Bueno, Gloria; Navarro, Samuel; Noguera, Rosa

2018-05-25

Neuroblastoma is the most common extra-cranial solid pediatric cancer and causes approximately 15% of all childhood deaths from cancer. Although lymphatic vasculature is a prerequisite for the maintenance of tissue fluid balance and immunity in the body, little is known about the relationship between lymphatic vascularization and prognosis in neuroblastoma. We used our previously-published custom-designed tool to close open-outline vessels and measure the density, size and shape of all lymphatic vessels and microvascular segments in 332 primary neuroblastoma contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological lymphatic vascular patterns associated with unfavorable histology. A high proportion of irregular intermediate lymphatic capillaries and irregular small collector vessels were present in tumors from patients with metastatic stage, undifferentiating neuroblasts and/or classified in the high risk. In addition, a higher lymphatic microvascularization density was found to be predictive of overall survival. Our findings show the crucial role of lymphatic vascularization in metastatic development and maintenance of tumor tissue homeostasis. These patterns may therefore help to indicate more accurate pre-treatment risk stratification and could provide candidate targets for novel therapies.

Advances in vascular tissue engineering.

PubMed

Thomas, Anita C; Campbell, Gordon R; Campbell, Julie H

2003-01-01

Coronary and peripheral artery bypass grafting is commonly used to relieve the symptoms of vascular deficiencies, but the supply of autologous artery or vein may not be sufficient or suitable for multiple bypass or repeat procedures, necessitating the use of other materials. Synthetic materials are suitable for large bore arteries but often thrombose when used in smaller arteries. Suitable replacement grafts must have appropriate characteristics, including resistance to infection, low immunogenicity and good biocompatability and thromboresistance, with appropriate mechanical and physiological properties and cheap and fast manufacture. Current avenues of graft development include coating synthetic grafts with either biological chemicals or cells with anticoagulatory properties. Matrix templates or acellular tubes of extracellular matrix (such as collagen) may be coated or infiltrated with cultured cells. Once placed into the artery, these grafts may become colonised by host cells and gain many of the properties of normal artery. "Tissue-engineered blood vessels" may also be formed from layers of human vascular cells grown in culture. These engineered vessels have many of the characteristics of arteries formed in vivo. "Artificial arteries" may be also be derived from peritoneal granulation tissue in body "bioreactors" by adapting the body's natural wound healing response to produce a hollow tube.

The Tissue-Engineered Vascular Graft—Past, Present, and Future

PubMed Central

Pashneh-Tala, Samand; MacNeil, Sheila

2016-01-01

Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented. PMID:26447530

Biomimicry, vascular restenosis and coronary stents.

PubMed

Schwartz, R S; van der Giessen, W J; Holmes, D R

1998-01-01

Biomimicry is in its earliest stages and is being considered in the realm of tissue engineering. If arterial implants are to limit neointimal thickening, purely passive structures cannot succeed. Bioactivity must be present, either by pharmacologic intervention or by fabricating a 'living stent' that contains active cellular material. As tissue engineering evolves, useful solutions will emerge from applying this knowledge directly to vascular biologic problems resulting from angioplasty, stenting, and vascular prosthesis research.

Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

PubMed

Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

2014-10-01

Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

Flow cytometry on the stromal-vascular fraction of white adipose tissue.

PubMed

Brake, Danett K; Smith, C Wayne

2008-01-01

Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow cytometry to analyze cell surface markers on leukocytes. Here, we present a technical approach to identify subsets of leukocytes that differentially express cell surface markers.

[Effect of fenicoberan on parameters of carbohydrate metabolism and electrolyte levels in blood vessel tissue].

PubMed

Puchkova, V A; Iakusheva, E N

1989-01-01

The spasmolysant fenicaberane was found to induce diverse changes in electrolyte levels, a significant increase of lactate content in all vascular zones, various changes in pyruvate levels depending on the vascular tissue type.

Outcomes of sympathectomy and vascular bypass for digital ischaemia in connective tissue disorders.

PubMed

Shammas, R L; Hwang, B H; Levin, L S; Richard, M J; Ruch, D S; Mithani, S K

2017-10-01

All patients (36 hands) with connective tissue disorders who underwent periarterial sympathectomy of the hand alone or in conjunction with vascular bypass at our institution between 1995-2013 were reviewed. The durable resolution of ulcers was significantly higher in patients treated by periarterial sympathectomy and bypass than in patients treated by periarterial sympathectomy alone. Although there were more digital amputations in patients treated by periarterial sympathectomy alone, the difference was not statistically significant. Vascular bypass in conjunction with sympathectomy may be better than sympathectomy alone in patients with digital ischaemia related to connective tissue disorders. IV.

Tissue-engineered vascular grafts composed of marine collagen and PLGA fibers using pulsatile perfusion bioreactors.

PubMed

Jeong, Sung In; Kim, So Yeon; Cho, Seong Kwan; Chong, Moo Sang; Kim, Kyung Soo; Kim, Hyuck; Lee, Sang Bong; Lee, Young Moo

2007-02-01

Novel tubular scaffolds of marine source collagen and PLGA fibers were fabricated by freeze drying and electrospinning processes for vascular grafts. The hybrid scaffolds, composed of a porous collagen matrix and a fibrous PLGA layer, had an average pore size of 150+/-50 microm. The electrospun fibrous PLGA layer on the surface of a porous tubular collagen scaffold improved the mechanical strength of the collagen scaffolds in both the dry and wet states. Smooth muscle cells (SMCs)- and endothelial cells (ECs)-cultured collagen/PLGA scaffolds exhibited mechanical properties similar to collagen/PLGA scaffolds unseeded with cells, even after culturing for 23 days. The effect of a mechanical stimulation on the proliferation and phenotype of SMCs and ECs, cultured on collagen/PLGA scaffolds, was evaluated. The pulsatile perfusion system enhanced the SMCs and ECs proliferation. In addition, a significant cell alignment in a direction radial to the distending direction was observed in tissues exposed to radial distention, which is similar to the phenomenon of native vessel tissues in vivo. On the other hand, cells in tissues engineered in the static condition were randomly aligned. Immunochemical analyses showed that the expressions of SM alpha-actin, SM myosin heavy chain, EC von Willebrand factor, and EC nitric oxide were upregulated in tissues engineered under a mechano-active condition, compared to vessel tissues engineered in the static condition. These results indicated that the co-culturing of SMCs and ECs, using collagen/PLGA hybrid scaffolds under a pulsatile perfusion system, leads to the enhancement of vascular EC development, as well as the retention of the differentiated cell phenotype.

Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds.

PubMed

Wang, Jianglin; Yang, Mingying; Zhu, Ye; Wang, Lin; Tomsia, Antoni P; Mao, Chuanbin

2014-08-06

A virus-activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high-density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tissue-engineered vascularized bone grafts: basic science and clinical relevance to trauma and reconstructive microsurgery.

PubMed

Johnson, Elizabeth O; Troupis, Theodore; Soucacos, Panayotis N

2011-03-01

Bone grafts are an important part of orthopaedic surgeon's armamentarium. Despite well-established bone-grafting techniques, large bone defects still represent a challenge. Efforts have therefore been made to develop osteoconductive, osteoinductive, and osteogenic bone-replacement systems. The long-term clinical goal in bone tissue engineering is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Current bone tissue engineering strategies take into account that bone is known for its ability to regenerate following injury, and for its intrinsic capability to re-establish a complex hierarchical structure during regeneration. Although the tissue engineering of bone for the reconstruction of small to moderate sized bone defects technically feasible, the reconstruction of large defects remains a daunting challenge. The essential steps towards optimized clinical application of tissue-engineered bone are dependent upon recent advances in the area of neovascularization of the engineered construct. Despite these recent advances, however, a gap from bench to bedside remains; this may ultimately be bridged by a closer collaboration between basic scientists and reconstructive surgeons. The aim of this review is to introduce the basic principles of tissue engineering of bone, outline the relevant bone physiology, and discuss the recent concepts for the induction of vascularization in engineered bone tissue. Copyright © 2011 Wiley-Liss, Inc.

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Globus, Ruth K.

2018-01-01

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and groundbased models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

Scabies in a bilateral hand allograft recipient: An additional mimicker of acute skin rejection in vascularized composite allotransplantation.

PubMed

Kanitakis, Jean; Morelon, Emmanuel

2017-06-01

Vascularized composite tissue allografts include skin, which frequently undergoes, in the early post-graft period, acute rejections. The diagnosis of acute rejection may be difficult as it can be mimicked by several dermatoses. We present a bilateral hand allograft recipient who developed, 16.5 years post-graft, cutaneous lesions raising suspicion about rejection. Physical examination and skin biopsy were diagnostic of scabies. This ectoparasitosis should be added in the list of dermatoses that can mimic allograft rejection in vascular composite allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.

PubMed

Borton, Anna Henry; Benson, Bryan L; Neilson, Lee E; Saunders, Ashley; Alaiti, M Amer; Huang, Alex Y; Jain, Mukesh K; Proweller, Aaron; Ramirez-Bergeron, Diana L

2018-06-01

Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia-inducible factors (HIFs) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells' (VSMCs') importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease. This study investigated the role of VSMC HIF in mediating peripheral ischemic responses. We used Arnt SMKO mice with smooth muscle-specific deletion of aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), required for HIF transcriptional activity, in a femoral artery ligation model of peripheral vascular disease. Arnt SMKO mice exhibit impaired perfusion recovery despite normal collateral vessel dilation and angiogenic capillary responses. Decreased blood flow manifests in extensive tissue damage and hypoxia in ligated limbs of Arnt SMKO mice. Furthermore, loss of aryl hydrocarbon receptor nuclear translocator changes the proliferation, migration, and transcriptional profile of cultured VSMCs. Arnt SMKO mice display disrupted VSMC morphologic features and wrapping around arterioles and increased vascular permeability linked to decreased local blood flow. Our data demonstrate that traditional vascular remodeling responses are insufficient to provide robust peripheral tissue reperfusion in Arnt SMKO mice. In all, this study highlights HIF responses to hypoxia in arteriole VSMCs critical for the phenotypic and functional stability of vessels that aid in the recovery of blood flow in ischemic peripheral tissues. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Immunolocalization of a Unique Form of Maize Kernel Glutamine Synthetase Using a Monoclonal Antibody.

PubMed Central

Muhitch, M. J.; Felker, F. C.; Taliercio, E. W.; Chourey, P. S.

1995-01-01

The pedicel (basal maternal tissue) of maize (Zea mays L.) kernels contains a physically and kinetically unique form of glutamine synthetase (GSp1) that is involved in the conversion of transport forms of nitrogen into glutamine for uptake by the developing endosperm (M.J. Muhitch [1989] Plant Physiol 91: 868-875). A monoclonal antibody has been raised against this kernel-specific GS that does not cross-react either with a second GS isozyme found in the pedicel or with the GS isozymes from the embryo, roots, or leaves. When used as a probe for tissue printing, the antibody labeled the pedicel tissue uniformly and also labeled some of the pericarp surrounding the lower endosperm. Silver-enhanced immunogold staining of whole-kernel paraffin sections revealed the presence of GSp1 in both the vascular tissue that terminates in the pedicel and the pedicel parenchyma cells, which are located between the vascular tissue and the basal endosperm transfer cells. Light staining of the subaleurone was also noted. The tissue-specific localization of GSp1 within the pedicel is consistent with its role in the metabolism of nitrogenous transport compounds as they are unloaded from the phloem. PMID:12228400

Longitudinal In Vivo Imaging to Assess Blood Flow and Oxygenation in Implantable Engineered Tissues

PubMed Central

White, Sean M.; Hingorani, Ryan; Arora, Rajan P.S.; Hughes, Christopher C.W.; George, Steven C.

2012-01-01

The functionality of vascular networks within implanted prevascularized tissues is difficult to assess using traditional analysis techniques, such as histology. This is largely due to the inability to visualize hemodynamics in vivo longitudinally. Therefore, we have developed dynamic imaging methods to measure blood flow and hemoglobin oxygen saturation in implanted prevascularized tissues noninvasively and longitudinally. Using laser speckle imaging, multispectral imaging, and intravital microscopy, we demonstrate that fibrin-based tissue implants anastomose with the host (severe combined immunodeficient mice) in as short as 20 h. Anastomosis results in initial perfusion with highly oxygenated blood, and an increase in average hemoglobin oxygenation of 53%. However, shear rates in the preformed vessels were low (20.8±12.8 s−1), and flow did not persist in the vast majority of preformed vessels due to thrombus formation. These findings suggest that designing an appropriate vascular network structure in prevascularized tissues to maintain shear rates above the threshold for thrombosis may be necessary to maintain flow following implantation. We conclude that wide-field and microscopic functional imaging can dynamically assess blood flow and oxygenation in vivo in prevascularized tissues, and can be used to rapidly evaluate and improve prevascularization strategies. PMID:22435776

Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development.

PubMed

Radke, Daniel; Jia, Wenkai; Sharma, Dhavan; Fena, Kemin; Wang, Guifang; Goldman, Jeremy; Zhao, Feng

2018-05-07

Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

PubMed Central

Gelfand, Bradley D.; Ambati, Jayakrishna

2016-01-01

Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

Cerebral oximetry in cardiac and major vascular surgery.

PubMed

Fischer, G W; Silvay, G

2010-01-01

We describe the development and current applications of cerebral oximetry (based on near-infrared reflectance spectroscopy) that can be used during cardiac and major vascular surgery to determined brain tissue oxygen saturation. There are presently three cerebral oximetry devices with FDA approval in the United States to measure and monitor cerebral tissue oxygen saturation. 1. INVOS (Somanetics Corporation, Troy, MI - recently COVIDIEN, Boulder, CO); FORE-SIGHT (CAS Medical Systems, Inc. Branford, CT); EQUANOX (Nonin Medical Inc.Minnesota, MN). All devices are portable, non-invasive and easy to use in operating room and intensive care unit. The data provided in these communication may provided information for improvement of perioperative neuromonitoring techniques, and may be crucial in the design of future clinical trials.

Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

PubMed

Krajnak, Kristine; Miller, G R; Waugh, Stacey

2018-01-01

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

Axon guidance molecules in vascular patterning.

PubMed

Adams, Ralf H; Eichmann, Anne

2010-05-01

Endothelial cells (ECs) form extensive, highly branched and hierarchically organized tubular networks in vertebrates to ensure the proper distribution of molecular and cellular cargo in the vertebrate body. The growth of this vascular system during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of endothelial cells in a process termed angiogenesis. Surprisingly, specialized ECs, so-called tip cells, which lead and guide endothelial sprouts, share many feature with another guidance structure, the axonal growth cone. Tip cells are motile, invasive and extend numerous filopodial protrusions sensing growth factors, extracellular matrix and other attractive or repulsive cues in their tissue environment. Axonal growth cones and endothelial tip cells also respond to signals belonging to the same molecular families, such as Slits and Roundabouts, Netrins and UNC5 receptors, Semaphorins, Plexins and Neuropilins, and Eph receptors and ephrin ligands. Here we summarize fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling.

* A Rat Model for the In Vivo Assessment of Biological and Tissue-Engineered Valvular and Vascular Grafts.

PubMed

Sugimura, Yukiharu; Schmidt, Anna Kathrin; Lichtenberg, Artur; Assmann, Alexander; Akhyari, Payam

2017-12-01

The demand for an improvement of the biocompatibility and durability of vascular and valvular implants requires translational animal models to study the in vivo fate of cardiovascular grafts. In the present article, a review on the development and application of a microsurgical rat model of infrarenal implantation of aortic grafts and aortic valved conduits is provided. By refinement of surgical techniques and inclusion of hemodynamic considerations, a functional model has been created, which provides a modular platform for the in vivo assessment of biological and tissue-engineered grafts. Through optional addition of procalcific diets, disease-inducing agents, and genetic modifications, complex multimorbidity scenarios mimicking the clinical reality in cardiovascular patients can be simulated. Applying this model, crucial aspects of the biocompatibility, biofunctionality and degeneration of vascular and valvular implants in dependency on graft preparation, and modification as well as systemic antidegenerative treatment of the recipient have been and will be addressed.

Vascular-mediated signalling involved in early phosphate stress response in plants.

PubMed

Zhang, Zhaoliang; Zheng, Yi; Ham, Byung-Kook; Chen, Jieyu; Yoshida, Akiko; Kochian, Leon V; Fei, Zhangjun; Lucas, William J

2016-04-04

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole-plant Pi homeostasis.

Air-spun PLA nanofibers modified with reductively sheddable hydrophilic surfaces for vascular tissue engineering: synthesis and surface modification.

PubMed

Ko, Na Re; Sabbatier, Gad; Cunningham, Alexander; Laroche, Gaétan; Oh, Jung Kwon

2014-02-01

Polylactide (PLA) is a class of promising biomaterials that hold great promise for various biological and biomedical applications, particularly in the field of vascular tissue engineering where it can be used as a fibrous mesh to coat the inside of vascular prostheses. However, its hydrophobic surface providing nonspecific interactions and its limited ability to further modifications are challenges that need to be overcome. Here, the development of new air-spun PLA nanofibers modified with hydrophilic surfaces exhibiting reduction response is reported. Surface-initiated atom transfer radical polymerization allows for grafting pendant oligo(ethylene oxide)-containing polymethacrylate (POEOMA) from PLA air-spun fibers labeled with disulfide linkages. The resulting PLA-ss-POEOMA fibers exhibit enhanced thermal stability and improved surface properties, as well as thiol-responsive shedding of hydrophilic POEOMA by the cleavage of its disulfide linkages in response to reductive reactions, thus tuning the surface properties. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vascular Regeneration in a Basal Chordate Is Due to the Presence of Immobile, Bi-Functional Cells

PubMed Central

Braden, Brian P.; Taketa, Daryl A.; Pierce, James D.; Kassmer, Susannah; Lewis, Daniel D.; De Tomaso, Anthony W.

2014-01-01

The source of tissue turnover during homeostasis or following injury is usually due to proliferation of a small number of resident, lineage-restricted stem cells that have the ability to amplify and differentiate into mature cell types. We are studying vascular regeneration in a chordate model organism, Botryllus schlosseri, and have previously found that following surgical ablation of the extracorporeal vasculature, new tissue will regenerate in a VEGF-dependent process within 48 hrs. Here we use a novel vascular cell lineage tracing methodology to assess regeneration in parabiosed individuals and demonstrate that the source of regenerated vasculature is due to the proliferation of pre-existing vascular resident cells and not a mobile progenitor. We also show that these cells are bi-potential, and can reversibly adopt two fates, that of the newly forming vessels or the differentiated vascular tissue at the terminus of the vasculature, known as ampullae. In addition, we show that pre-existing vascular resident cells differentially express progenitor and differentiated cell markers including the Botryllus homologs of CD133, VEGFR-2, and Cadherin during the regenerative process. PMID:24736432

Resection and reconstruction of pelvic and extremity soft tissue sarcomas with major vascular involvement: Current concepts

PubMed Central

McGoldrick, Niall P; Butler, Joseph S; Lavelle, Maire; Sheehan, Stephen; Dudeney, Sean; O'Toole, Gary C

2016-01-01

Soft tissue sarcoma accounts for approximately 1% of all cancers diagnosed annually in the United States. When these rare malignant mesodermal tumours arise in the pelvis and extremities, they may potentially encase or invade large calibre vascular structures. This presents a major challenge in terms of safe excision while also leaving acceptable surgical margins. In recent times, the trend has been towards limb salvage with vascular reconstruction in preference to amputation. Newer orthopaedic and vascular reconstructive techniques including both synthetic and autogenous graft reconstruction have made complex limb-salvage surgery feasible. Despite this, limb-salvage surgery with concomitant vascular reconstruction remains associated with higher rates of post-operative complications including infection and amputation. In this review we describe the initial presentation and investigation of patients presenting with soft tissue sarcomas in the pelvis and extremities, which involve vascular structures. We further discuss the key surgical reconstructive principles and techniques available for the management of these complex tumours, drawn from our institution’s experience as a national tertiary referral sarcoma service. PMID:27190757

Resection and reconstruction of pelvic and extremity soft tissue sarcomas with major vascular involvement: Current concepts.

PubMed

McGoldrick, Niall P; Butler, Joseph S; Lavelle, Maire; Sheehan, Stephen; Dudeney, Sean; O'Toole, Gary C

2016-05-18

Soft tissue sarcoma accounts for approximately 1% of all cancers diagnosed annually in the United States. When these rare malignant mesodermal tumours arise in the pelvis and extremities, they may potentially encase or invade large calibre vascular structures. This presents a major challenge in terms of safe excision while also leaving acceptable surgical margins. In recent times, the trend has been towards limb salvage with vascular reconstruction in preference to amputation. Newer orthopaedic and vascular reconstructive techniques including both synthetic and autogenous graft reconstruction have made complex limb-salvage surgery feasible. Despite this, limb-salvage surgery with concomitant vascular reconstruction remains associated with higher rates of post-operative complications including infection and amputation. In this review we describe the initial presentation and investigation of patients presenting with soft tissue sarcomas in the pelvis and extremities, which involve vascular structures. We further discuss the key surgical reconstructive principles and techniques available for the management of these complex tumours, drawn from our institution's experience as a national tertiary referral sarcoma service.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

PubMed

Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

2017-04-01

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have become of interest due to their ability to supplement tissue engineered scaffolds. Their ability to differentiate into cells of vascular lineages with defined phenotypes serves as a potential solution to a major cause of graft failure in which phenotypic shifts in smooth muscle cells lead to over proliferation and occlusion of the graft. Herein, we have differentiated human induced-pluripotent stem cells in a pulsatile flow bioreactor, resulting in vascular smooth muscle tissue with robust elastic fibers and enhanced functionality. This study highlights an effective approach to engineering elastic functional vascular smooth muscle tissue for tissue engineering and regenerative medicine applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Design of biomimetic vascular grafts with magnetic endothelial patterning.

PubMed

Fayol, Delphine; Le Visage, Catherine; Ino, Julia; Gazeau, Florence; Letourneur, Didier; Wilhelm, Claire

2013-01-01

The development of small diameter vascular grafts with a controlled pluricellular organization is still needed for effective vascular tissue engineering. Here, we describe a technological approach combining a tubular scaffold and magnetically labeled cells to create a pluricellular and organized vascular graft, the endothelialization of which could be monitored by MRI prior to transplantation. A novel type of scaffold was developed with a tubular geometry and a porous bulk structure enabling the seeding of cells in the scaffold pores. A homogeneous distribution of human mesenchymal stem cells in the macroporous structure was obtained by seeding the freeze-dried scaffold with the cell suspension. The efficient covering of the luminal surface of the tube was then made possible thanks to the implementation of a magnetic-based patterning technique. Human endothelial cells or endothelial progenitors were magnetically labeled with iron oxide nanoparticles and successfully attracted to the 2-mm lumen where they attached and formed a continuous endothelium. The combination of imaging modalities [fluorescence imaging, histology, and 3D magnetic resonance imaging (MRI)] evidenced the integrity of the vascular construct. In particular, the observation of different cell organizations in a vascular scaffold within the range of resolution of single cells by 4.7 T MRI is reported.

[Direct and indirect somatic embryogenesis in Freesia refracta].

PubMed

Wang, L; Duan, X G; Hao, S

1999-06-01

Somatic embryogenesis can be induced in tissue cultures of Freesia refracta either directly from the epidermal cells of explant, or indirectly via intervening callus. In direct pathway, somatic embryos were in contact with maternal tissue in a suspensor-like structure. In indirect pathway, the explants first proliferacted to give rise to calluses before embryoids were induced. The two sorts of calluses were defined to embryogenic callus and non-embryogenic callus according to producing of somatic embryos. An indirect somatic embryo is developed from a pre-embryogenically determined cell. This kind of somatic embryo has no suspensor structure instead of a complex with maternal tissue. Somatic embryos have their own vascular tissues, and can develop new plantlets independently.

Development and characterization of hybrid tubular structure of PLCL porous scaffold with hMSCs/ECs cell sheet.

PubMed

Pangesty, Azizah Intan; Arahira, Takaaki; Todo, Mitsugu

2017-09-15

Tissue engineering offers an alternate approach to providing vascular graft with potential to grow similar with native tissue by seeding autologous cells into biodegradable scaffold. In this study, we developed a combining technique by layering a sheet of cells onto a porous tubular scaffold. The cell sheet prepared from co-culturing human mesenchymal stem cells (hMSCs) and endothelial cells (ECs) were able to infiltrate through porous structure of the tubular poly (lactide-co-caprolactone) (PLCL) scaffold and further proliferated on luminal wall within a week of culture. Moreover, the co-culture cell sheet within the tubular scaffold has demonstrated a faster proliferation rate than the monoculture cell sheet composed of MSCs only. We also found that the co-culture cell sheet expressed a strong angiogenic marker, including vascular endothelial growth factor (VEGF) and its receptor (VEGFR), as compared with the monoculture cell sheet within 2 weeks of culture, indicating that the co-culture system could induce differentiation into endothelial cell lineage. This combined technique would provide cellularization and maturation of vascular construct in relatively short period with a strong expression of angiogenic properties.

Lung assist device technology with physiologic blood flow developed on a tissue engineered scaffold platform.

PubMed

Hoganson, David M; Pryor, Howard I; Bassett, Erik K; Spool, Ira D; Vacanti, Joseph P

2011-02-21

There is no technology available to support failing lung function for patients outside the hospital. An implantable lung assist device would augment lung function as a bridge to transplant or possible destination therapy. Utilizing biomimetic design principles, a microfluidic vascular network was developed for blood inflow from the pulmonary artery and blood return to the left atrium. Computational fluid dynamics analysis was used to optimize blood flow within the vascular network. A micro milled variable depth mold with 3D features was created to achieve both physiologic blood flow and shear stress. Gas exchange occurs across a thin silicone membrane between the vascular network and adjacent alveolar chamber with flowing oxygen. The device had a surface area of 23.1 cm(2) and respiratory membrane thickness of 8.7 ± 1.2 μm. Carbon dioxide transfer within the device was 156 ml min(-1) m(-2) and the oxygen transfer was 34 ml min(-1) m(-2). A lung assist device based on tissue engineering architecture achieves gas exchange comparable to hollow fiber oxygenators yet does so while maintaining physiologic blood flow. This device may be scaled up to create an implantable ambulatory lung assist device.

Development and Optimization of Viable Human Platforms through 3D Printing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, Paul R.; Moya, Monica L.; Wheeler, Elizabeth K.

2015-08-21

3D printing technology offers a unique method for creating cell cultures in a manner far more conducive to accurate representation of human tissues and systems. Here we print cellular structures capable of forming vascular networks and exhibiting qualities of natural tissues and human systems. This allows for cheaper and readily available sources for further study of biological and pharmaceutical agents.

Arterial complications of vascular Ehlers-Danlos syndrome.

PubMed

Eagleton, Matthew J

2016-12-01

Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect the soft connective tissues resulting in abnormalities in the skin, joints, hollow organs, and blood vessels. Patients with these defects frequently present at a young age with spontaneous arterial complications involving the medium-sized arteries. Complications involving the hollow organs, such as spontaneous colonic perforation, are observed as well. Given the fragility of the soft tissue, open and endovascular intervention on patients with vascular EDS is fraught with high complication rates. A PubMed search was performed to identify manuscripts published related to vascular EDS. This search included more than 747 articles. These findings were cross-referenced using key terms, including endovascular, embolization, surgery, genetics, pathophysiology, connective tissue disorders, vascular complications, systematic review, type III collagen, and COL3A1. The references in key articles and review articles were evaluated for additional resources not identified in the PubMed search. Care must be taken to balance the risk of intervention vs the risk of continued observation. Life-threatening hemorrhage, however, mandates intervention. With careful, altered approaches to tissue handling, endovascular approaches may provide a safer option for managing the arterial complications observed in patients with vascular EDS. Additional hope may also be found in the use of pharmacologic agents that reduce the incidence and severity of the arterial complications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

PubMed Central

Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

PubMed

Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

PubMed

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

PubMed Central

Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

A model describing diffusion in prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-07-01

Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill-defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non-Gaussian behavior of tissue diffusion. The model assumes that exchange between the cellular (ie, stromal plus epithelial) and the vascular and ductal compartments is slow. Ductal and cellular diffusion characteristics are estimated by Monte Carlo simulation and a two-compartment exchange model, respectively. Vascular pseudodiffusion is represented by an additional signal at b = 0. Most model parameters are obtained either from published data or by comparing model predictions with the published results from 41 studies. Model prediction error is estimated using 10-fold cross-validation. Agreement between model predictions and published results is good. The model satisfactorily explains the variability of ADC estimates found in the literature. A reliable model that predicts the diffusion behavior of benign and cancerous prostate tissue of different Gleason scores has been developed. Magn Reson Med 78:316-326, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Seeding arterial prostheses with vascular endothelium. The nature of the lining.

PubMed Central

Herring, M B; Dilley, R; Jersild, R A; Boxer, L; Gardner, A; Glover, J

1979-01-01

Arterial prostheses seeded with autogenous vascular endothelium demonstrate a well-organized, cellular, inner lining. To determine the nature of the lining cells, six animals underwent replacement of the infrarenal aorta with Dacron prostheses. During the preparation of three such grafts, endothelium was scraped from the saphenous vein with a steel wool pledget, suspended in chilled Sack's solution, and mixed with blood used to preclot the graft. This suspension was omitted from the three control grafts. After six weeks, the grafts were removed, rinsed and examined. Fluorescent Factor VIII related antigen (F VIII-RA) strongly stained the lining cells. Silver nitrate Haütchen and electron microscopy preparations revealed a lining pattern characteristic of vascular endothelium. Endothelial cell-specific Weibel-Palade bodies were identified in the lining cell cytoplasm. Masson's trichrome staining revealed a relatively collagen-poor connective tissue within the seeded fabric. Transmission electron microscopy disclosed vascular smooth muscle cells between the seeded graft fabric and the lining cells. Vasa vasorum, arising from the outer capsule, penetrated the fabric to supply the inner capsules of the seeded grafts. It is concluded that the cells lining seeded canine arterial prostheses are true vascular endothelium supported by vascular smooth muscle cells, that the lining contains minimal connective tissue, and that vasa vasorum develop. Unseeded control grafts lacked these features. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:464684

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

2010-01-01

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of humans, animals and plants is significantly modified in such extraterrestrial environments. One physiological requirement shared by humans with larger plants and animals is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. The VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P. A.; Vickerman, M. B.; Keith, P. A.

2010-01-01

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of plants, animals and humans is significantly modified in such extraterrestrial environments. One physiological requirement shared by larger plants and animals with humans is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Expert Opinion Editorial Tissue Engineered Blood Vessels as Promising Tools for Testing Drug Toxicity

PubMed Central

Truskey, George A.; Fernandez, Cristina E.

2015-01-01

Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI. Small scale endothelialized tissue-engineered blood vessels using human cells represent a promising approach to screen drug candidates and developed alternatives to cancer therapeutics in vitro. We identify several technical challenges that remain to be addressed, including high throughput systems to screen large numbers of candidates, identification of suitable cell sources, and establishing and maintaining a differentiated state of the vessel wall cells. Adequately addressing these challenges should yield novel platforms to screen drugs and develop new therapeutics to treat cardiovascular disease. PMID:26028128

Age-related macular degeneration: beyond anti-angiogenesis.

PubMed

Kent, David L

2014-01-06

Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate vascular maturation, rather than its arrest or destruction. This would neutralize hypoxia, thus removing the stimulus that drives neovascularization and in turn the need for repeated lifelong intravitreal therapy. A pro-angiogenic approach would eliminate neovascular leakage and ultimately complete repair and preserve the neurosensory retina.

Collagen vascular disease

MedlinePlus

... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many ...

Biomaterials in myocardial tissue engineering

PubMed Central

Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

2016-01-01

Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

Angiogenesis and microvasculature in the female reproductive organs: physiological and pathological implications.

PubMed

Shimizu, Takashi; Hoshino, Yumi; Miyazaki, Hitoshi; Sato, Eimei

2012-01-01

The female reproductive organs such as ovary, uterus, and placenta are some of the few adult tissues that exhibit regular intervals of rapid growth, and are highly vascularized and have high rates of blood flow. Angiogenesis is a process of vascular growth that is mainly limited to the reproductive system in healthy adult animals. The development of new blood vessels in the ovary and uterus is essential to guarantee the necessary supply of nutrients and hormones. The genetic and molecular mechanisms that control the development of capillary blood vessels in the reproductive organs are beginning to be elucidated. Reproductive organs contain and produce angiogenic factors which may act alone or in concert to regulate the process of vasculature. Vascular endothelial growth factors (VEGFs) and fibroblast growth factor (FGFs) are key factors for vascular system in the reproductive organs. Recent numerous studies reported several roles of VEGFs and FGFs on ovarian and uterine functions. In this review, we focus on the involvement of VEGFs and FGFs as angiogenic factors on reproductive organs and vascular therapy for diseases of reproductive organs using anti-angiogenic agents.

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

PubMed

Lanham, S A; Cagampang, F R; Oreffo, R O C

2014-12-01

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization.

PubMed

Gucciardo, Erika; Loukovaara, Sirpa; Korhonen, Ani; Repo, Pauliina; Martins, Beatriz; Vihinen, Helena; Jokitalo, Eija; Lehti, Kaisa

2018-06-01

Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady-state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions. We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analysed ex vivo and related to clinical data. As characterized by three-dimensional whole-mount immunofluorescence and electron microscopy, heterogeneity in patient-derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic-like and tortuous endothelia. Spatially confined apoptosis and proliferation coexisted with inflammatory cell infiltration and unique vascular islet formation. Ex vivo-cultured explants retained multicellularity, islet patterning and capillary or fibrotic outgrowth in response to vitreoretinal factors. Strikingly, PDR neovascular tissues, whose matched vitreous samples enhanced lymphatic endothelial cell sprouting, contained lymphatic-like capillaries in vivo and developed Prox1 + capillaries and sprouts with lymphatic endothelial ultrastructures ex vivo. Among multiple vitreal components, vascular endothelial growth factor C was one factor found at lymphatic endothelium-activating concentrations. These results indicate that the ischaemia-induced and inflammation-induced human PDR microenvironment supports pathological neolymphovascularization, providing a new concept regarding PDR mechanisms and targeting options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

PubMed Central

Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

Screening phage display libraries for organ-specific vascular immunotargeting in vivo

PubMed Central

Valadon, Philippe; Garnett, Jeff D.; Testa, Jacqueline E.; Bauerle, Marc; Oh, Phil; Schnitzer, Jan E.

2006-01-01

The molecular diversity of the luminal endothelial cell surface arising in vivo from local variations in genetic expression and tissue microenvironment may create opportunities for achieving targeted molecular imaging and therapies. Here, we describe a strategy to identify probes and their cognate antigens for targeting vascular endothelia of specific organs in vivo. We differentially screen phage libraries to select organ-targeting antibodies by using luminal endothelial cell plasma membranes isolated directly from tissue and highly enriched in natively expressed proteins exposed to the bloodstream. To obviate liver uptake of intravenously injected phage, we convert the phage-displayed antibodies into scFv-Fc fusion proteins, which then are able to rapidly target select organ(s) in vivo as visualized directly by γ-scintigraphic whole-body imaging. Mass spectrometry helps identify the antigen targets. This comprehensive strategy provides new promise for harnessing the power of phage display for mapping vascular endothelia natively in tissue and for achieving vascular targeting of specific tissues in vivo. PMID:16384919

Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development.

PubMed

Mastrangelo, F; Sberna, M T; Tettamanti, L; Cantatore, G; Tagliabue, A; Gherlone, E

2016-01-01

Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis.

Towards cavitation-enhanced permeability in blood vessel on a chip

NASA Astrophysics Data System (ADS)

De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

2017-08-01

The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature.

PubMed

Chou, Cheng-Ying; Chang, Wan-I; Horng, Tzyy-Leng; Lin, Win-Li

2017-01-01

The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.

Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration

PubMed Central

Masumoto, Hidetoshi; Ikuno, Takeshi; Takeda, Masafumi; Fukushima, Hiroyuki; Marui, Akira; Katayama, Shiori; Shimizu, Tatsuya; Ikeda, Tadashi; Okano, Teruo; Sakata, Ryuzo; Yamashita, Jun K.

2014-01-01

To realize cardiac regeneration using human induced pluripotent stem cells (hiPSCs), strategies for cell preparation, tissue engineering and transplantation must be explored. Here we report a new protocol for the simultaneous induction of cardiomyocytes (CMs) and vascular cells [endothelial cells (ECs)/vascular mural cells (MCs)], and generate entirely hiPSC-engineered cardiovascular cell sheets, which showed advantageous therapeutic effects in infarcted hearts. The protocol adds to a previous differentiation protocol of CMs by using stage-specific supplementation of vascular endothelial cell growth factor for the additional induction of vascular cells. Using this cell sheet technology, we successfully generated physically integrated cardiac tissue sheets (hiPSC-CTSs). HiPSC-CTS transplantation to rat infarcted hearts significantly improved cardiac function. In addition to neovascularization, we confirmed that engrafted human cells mainly consisted of CMs in >40% of transplanted rats four weeks after transplantation. Thus, our HiPSC-CTSs show promise for cardiac regenerative therapy. PMID:25336194

Fluorinated polyurethane scaffolds for 19F magnetic resonance imaging

PubMed Central

Rahimi, Khosrow; Shi, Yang; Schulz, Volkmar; Kuehne, Alexander J. C.; Jockenhoevel, Stefan; Kiessling, Fabian

2017-01-01

Polymers are increasingly employed in implant materials. To reduce the incidence of complications, which in the case of vascular grafts include incorrect placement and restenosis, materials are needed which allow for image-guided implantation, as well as for accurate and efficient postoperative implant imaging. We here describe amorphous fluorinated polymers based on thermoplastic polyurethane (19F-TPU), and show that are useful starting materials for developing tissue-engineered vascular grafts which can be detected using 19F MRI. PMID:28413258

Review paper: critical issues in tissue engineering: biomaterials, cell sources, angiogenesis, and drug delivery systems.

PubMed

Naderi, Hojjat; Matin, Maryam M; Bahrami, Ahmad Reza

2011-11-01

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

A comparative study of the chondrogenic potential between synthetic and natural scaffolds in an in vivo bioreactor

NASA Astrophysics Data System (ADS)

Huang, Jung-Ju; Yang, Shu-Rui; Chu, I.-Ming; Brey, Eric M.; Hsiao, Hui-Yi; Cheng, Ming-Huei

2013-10-01

The clinical demand for cartilage tissue engineering is potentially large for reconstruction defects resulting from congenital deformities or degenerative disease due to limited donor sites for autologous tissue and donor site morbidities. Cartilage tissue engineering has been successfully applied to the medical field: a scaffold pre-cultured with chondrocytes was used prior to implantation in an animal model. We have developed a surgical approach in which tissues are engineered by implantation with a vascular pedicle as an in vivo bioreactor in bone and adipose tissue engineering. Collagen type II, chitosan, poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were four commonly applied scaffolds in cartilage tissue engineering. To expand the application of the same animal model in cartilage tissue engineering, these four scaffolds were selected and compared for their ability to generate cartilage with chondrocytes in the same model with an in vivo bioreactor. Gene expression and immunohistochemistry staining methods were used to evaluate the chondrogenesis and osteogenesis of specimens. The result showed that the PLGA and PCL scaffolds exhibited better chondrogenesis than chitosan and type II collagen in the in vivo bioreactor. Among these four scaffolds, the PCL scaffold presented the most significant result of chondrogenesis embedded around the vascular pedicle in the long-term culture incubation phase.

Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.

PubMed

Barry, Christopher; Schmitz, Matthew T; Propson, Nicholas E; Hou, Zhonggang; Zhang, Jue; Nguyen, Bao K; Bolin, Jennifer M; Jiang, Peng; McIntosh, Brian E; Probasco, Mitchell D; Swanson, Scott; Stewart, Ron; Thomson, James A; Schwartz, Michael P; Murphy, William L

2017-11-01

The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies. Spearman's rank correlation analysis of global gene expression profiles and a comparison of coefficient of variation for expressed genes demonstrated that replicate neural constructs were highly uniform to at least day 21 for samples from independent experiments. We also demonstrate that model neural tissues formed on PEG hydrogels using a simplified neural differentiation protocol correlated more strongly to in vivo brain development than samples cultured on tissue culture polystyrene surfaces alone. These results provide a proof-of-concept demonstration that 3D cellular models that mimic aspects of human brain development can be produced from human pluripotent stem cells with high sample uniformity between experiments by using standard culture techniques, cryopreserved cell stocks, and a synthetic extracellular matrix. Impact statement Pluripotent stem (PS) cells have been characterized by an inherent ability to self-organize into 3D "organoids" resembling stomach, intestine, liver, kidney, and brain tissues, offering a potentially powerful tool for modeling human development and disease. However, organoid formation must be quantitatively reproducible for applications such as drug and toxicity screening. Here, we report a strategy to produce uniform neural tissue constructs with reproducible global gene expression profiles for replicate samples from multiple experiments.

Strength and Persistence of Energy-Based Vessel Seals Rely on Tissue Water and Glycosaminoglycan Content.

PubMed

Kramer, Eric A; Cezo, James D; Fankell, Douglas P; Taylor, Kenneth D; Rentschler, Mark E; Ferguson, Virginia L

2016-11-01

Vessel ligation using energy-based surgical devices is steadily replacing conventional closure methods during minimally invasive and open procedures. In exploring the molecular nature of thermally-induced tissue bonds, novel applications for surgical resection and repair may be revealed. This work presents an analysis of the influence of unbound water and hydrophilic glycosaminoglycans on the formation and resilience of vascular seals via: (a) changes in pre-fusion tissue hydration, (b) the enzymatic digestion of glycosaminoglycans (GAGs) prior to fusion and (c) the rehydration of vascular seals following fusion. An 11% increase in pre-fusion unbound water led to an 84% rise in vascular seal strength. The digestion of GAGs prior to fusion led to increases of up to 82% in seal strength, while the rehydration of native and GAG-digested vascular seals decreased strengths by 41 and 44%, respectively. The effects of increased unbound water content prior to fusion combined with the effects of seal rehydration after fusion suggest that the heat-induced displacement of tissue water is a major contributor to tissue adhesion during energy-based vessel sealing. The effects of pre-fusion GAG-digestion on seal integrity indicate that GAGs are inhibitory to the bond formation process during thermal ligation. GAG digestion may allow for increased water transport and protein interaction during the fusion process, leading to the formation of stronger bonds. These findings provide insight into the physiochemical nature of the fusion bond, its potential for optimization in vascular closure and its application to novel strategies for vascular resection and repair.

Encapsulation of Mesenchymal Stem Cells Improves Vascularization of Alginate-Based Scaffolds.

PubMed

Steiner, Dominik; Lingens, Lara; Fischer, Laura; Köhn, Katrin; Detsch, Rainer; Boccaccini, Aldo R; Fey, Tobias; Greil, Peter; Weis, Christian; Beier, Justus P; Horch, Raymund E; Arkudas, Andreas

2018-05-09

Vascularization of bioartificial tissues can be significantly enhanced by the generation of an arteriovenous (AV) loop. Besides the surgical vascularization, the choice of the scaffold and the applied cells are indispensable cofactors. The combination of alginate dialdehyde and gelatin (ADA-GEL) and mesenchymal stem cells (MSCs) is a promising approach with regard to biocompatibility, biodegradation, as well as de novo tissue formation. In this study, we targeted the investigation of the vascularization of ADA-GEL with and in the absence of encapsulated MSCs in the AV loop model. A Teflon chamber filled with ADA-GEL microcapsules was placed in the groin of Lewis rats and an AV loop was placed into the chamber. Group A encompassed the ADA-GEL without MSCs, whereas group B contained 2 × 10 6 DiI-labeled MSCs/mL ADA-GEL. Four weeks postoperatively, tissue formation and vascularization were investigated by histology and microcomputed tomography. We were able to prove vascularization originating from the AV loop in both groups with statistically significant more vessels in group B containing MSCs. Moreover, encapsulated MSCs promoted biodegradation of the ADA-GEL microcapsules. In the present study, we were able to demonstrate for the first time, the successful vascularization of ADA-GEL microcapsules by means of the AV loop. Furthermore, ADA-GEL displayed a good biocompatibility and encapsulation of MSCs into ADA-GEL microcapsule-enhanced vascularization as well as biodegradation.

Avian Blood-Vessel Formation in Space

NASA Technical Reports Server (NTRS)

Lelkes, Peter I.

1999-01-01

Based on previous studies, we hypothesized that the developmental anomalies observed in the past might be related to or caused by delayed or improper vascular development. The objective of our research is to test the hypothesis that exposure to microgravity during space flight cause delayed or improper vascular development during embryogenesis. The effects of microgravity on the time course and extent of avian blood-vessel formation are assessed using two models, one for angiogenesis and one for vasculogenesis. The methodological approach is dictated by the constraints of the tissue preservation method used in space. Thus, both in the chorioallantoic membrane (CAM) and in the adrenal, we will evaluate microscopically the vascular architecture and immunostain endothelial cells with specific antibodies (anti- vWF and QH1). The extent of ECM protein deposition will be assessed by immunohistochemistry and correlated with the degree of vascularization, using computer-based image analysis. Also, the cellular source for ECM proteins will be assessed by in situ hybridization.

Quantitative analysis of [99mTc]C2A-GST distribution in the area at risk after myocardial ischemia and reperfusion using a compartmental model.

PubMed

Audi, Said; Poellmann, Michael; Zhu, Xiaoguang; Li, Zhixin; Zhao, Ming

2007-11-01

It was recently demonstrated that the radiolabeled C2A domain of synaptotagmin I accumulates avidly in the area at risk after ischemia and reperfusion. The objective was to quantitatively characterize the dynamic uptake of radiolabeled C2A in normal and ischemically injured myocardia using a compartmental model. To induce acute myocardial infarction, the left descending coronary artery was ligated for 18 min, followed by reperfusion. [99mTc]C2A-GST or its inactivated form, [99mTc]C2A-GST-NHS, was injected intravenously at 2 h after reperfusion. A group of four rats was sacrificed at 10, 30, 60 and 180 after injection. Uptake of [99mTc]C2A-GST and [99mTc]C2A-GST-NHS in the area at risk and in the normal myocardium were determined by gamma counting. A compartmental model was developed to quantitatively interpret myocardial uptake kinetic data. The model consists of two physical spaces (vascular space and tissue space), with plasma activity as input. The model allows for [99mTc]C2A-GST and [99mTc]C2A-GST-NHS diffusion between vascular and tissue spaces, as well as for [99mTc]C2A-GST sequestration in vascular and tissue spaces via specific binding. [99mTc]C2A-GST uptake in the area at risk was significantly higher than that for [99mTc]C2A-GST-NHS at all time points. The compartmental model separated [99mTc]C2A-GST uptake in the area at risk due to passive retention from that due to specific binding. The maximum amount of [99mTc]C2A-GST that could be sequestered in the area at risk due to specific binding was estimated at a total of 0.048 nmol/g tissue. The rate of [99mTc]C2A-GST sequestration within the tissue space of the area at risk was 0.012 ml/min. Modeling results also revealed that the diffusion rate of radiotracer between vascular and tissue spaces is the limiting factor of [99mTc]C2A-GST sequestration within the tissue space of the area at risk. [99mTc]C2A-GST is sequestered in the ischemically injured myocardium in a well-defined dynamic profile. Model parameters will be valuable indicators for gauging and guiding the development of future-generation molecular probes.

Attempts to Localize and Identify the Gravity-sensing Device of Plant Seedlings

NASA Technical Reports Server (NTRS)

Bandurski, R. S.; Schulze, A.; Momonoki, Y.; Desrosiers, M.; Fearn-Desrosiers, D.

1985-01-01

The growth hormone asymmetry develops within three minutes following the initiation of the gravitational asymmetry and radio-labeled compounds being transported from the seed to the shoot also show asymmetric distribution. It is found that the target of the gravity stimulus resides primarily in the permability of the vascular tissue that regulates the supply of hormone to the surrounding tissues. It is hypothesized that the gravitational stimulus induces an asymmetric change in the rate of secretion of the growth hormone, IAA, from the vascular tissue into the surrounding cortical cells. More hormone would be secreted from the vascular stele proximal to the lower side of a horizontally placed plant shoot than from the upper side. This results in more growth hormone in the lower cortical (plus epidermal) cells, and ultimately more growth, such that the plant grows asymmetrically and, ultimately attain its normal vertical orientation. A theory was developed of how plants respond to the gravitational stimulus. The theory is based upon the analytical results concerning the effects of gravity on the distribution of the plant growth hormone, IAA, in both its free and conjugated forms, and upon the effect of the growth stimulis on the distribution of externally applied radio-labeled compounds. Its advantage is that it is testable and that it is built upon solid knowledge of the effects of the gravitational stimulus upon the endogenous growth hormone, IAA, and upon the distribution of externally applied radio-labeled compounds.

Characterization of evolving biomechanical properties of tissue engineered vascular grafts in the arterial circulation.

PubMed

Udelsman, Brooks V; Khosravi, Ramak; Miller, Kristin S; Dean, Ethan W; Bersi, Matthew R; Rocco, Kevin; Yi, Tai; Humphrey, Jay D; Breuer, Christopher K

2014-06-27

We used a murine model to assess the evolving biomechanical properties of tissue engineered vascular grafts (TEVGs) implanted in the arterial circulation. The initial polymeric tubular scaffold was fabricated from poly(lactic acid)(PLA) and coated with a 50:50 copolymer of poly(caprolactone) and poly(lactic acid)(P[PC/LA]). Following seeding with syngeneic bone marrow derived mononuclear cells, TEVGs (n=50) were implanted as aortic interposition grafts in wild-type mice and monitored serially using ultrasound. A custom biaxial mechanical testing device was used to quantify the in vitro circumferential and axial mechanical properties of grafts explanted at 3 or 7 months. At both times, TEVGs were much stiffer than native tissue in both directions. Repeated mechanical testing of some TEVGs treated with elastase or collagenase suggested that elastin did not contribute significantly to the overall stiffness whereas collagen did contribute. Traditional histology and immunostaining revealed smooth muscle cell layers, significant collagen deposition, and increasing elastin production in addition to considerable scaffold at both 3 and 7 months, which likely dominated the high stiffness seen in mechanical testing. These results suggest that PLA has inadequate in vivo degradation, which impairs cell-mediated development of vascular neotissue having properties closer to native arteries. Assessing contributions of individual components, such as elastin and collagen, to the developing neovessel is needed to guide computational modeling that may help to optimize the design of the TEVG. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix.

PubMed

Jusoh, Norhana; Oh, Soojung; Kim, Sudong; Kim, Jangho; Jeon, Noo Li

2015-10-21

Current in vitro systems mimicking bone tissues fail to fully integrate the three-dimensional (3D) microvasculature and bone tissue microenvironments, decreasing their similarity to in vivo conditions. Here, we propose 3D microvascular networks in a hydroxyapatite (HA)-incorporated extracellular matrix (ECM) for designing and manipulating a vascularized bone tissue model in a microfluidic device. Incorporation of HA of various concentrations resulted in ECM with varying mechanical properties. Sprouting angiogenesis was affected by mechanically modulated HA-extracellular matrix interactions, generating a model of vascularized bone microenvironment. Using this platform, we observed that hydroxyapatite enhanced angiogenic properties such as sprout length, sprouting speed, sprout number, and lumen diameter. This new platform integrates fibrin ECM with the synthetic bone mineral HA to provide in vivo-like microenvironments for bone vessel sprouting.

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis.

PubMed

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-10-15

Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD + -dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis.

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis

PubMed Central

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-01-01

Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD+-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis. PMID:27744418

Preventing the infiltration of leukocytes by monoclonal antibody blocks the development of progressive ischemia in rat burns.

PubMed

Choi, M; Rabb, H; Arnaout, M A; Ehrlich, H P

1995-10-01

Tissue loss as a consequence of thermal trauma occurs in two stages. There is immediate necrosis in tissues directly killed by the thermal energy, followed by a delayed secondary necrosis in neighboring tissues. The infiltration of neutrophils into traumatized tissues is a hallmark of the inflammatory response. Neutrophils have the machinery to kill invading microorganisms, but these same weapons have the capacity to destroy the host's viable tissues as well. Leukocyte infiltration requires their adherence to the vascular endothelial cell surface. Masking these adhesion sites on neutrophils will block the adhesion of neutrophils to the endothelium. A monoclonal antibody (mAb) was developed to guinea pig leukocyte adhesion sites CD11b/ CD18, and this mAb cross-reacts with rat leukocytes, blocking their adherence. Rats received a "comb burn" composed of four rectangular full-thickness burns placed in a row and separated by three areas left unburned. The four individual burns convert into a single large wound because the blood flow to the interspaces was terminated, blood vessels were occluded, and leukocytes were present in the extravascular space. The systemic administration of the mAb (50 to 150 microliters) immediately following a comb burn promoted the survival of the interspace, demonstrated by the prevention of loss of blood flow by laser Doppler monitoring, maintained patent vessels by latex vascular casts, blocked extravascular migration of neutrophils histologically at 2 hours, and limited the tissue loss to the original four burns.

Specialized mouse embryonic stem cells for studying vascular development.

PubMed

Glaser, Drew E; Burns, Andrew B; Hatano, Rachel; Medrzycki, Magdalena; Fan, Yuhong; McCloskey, Kara E

2014-01-01

Vascular progenitor cells are desirable in a variety of therapeutic strategies; however, the lineage commitment of endothelial and smooth muscle cell from a common progenitor is not well-understood. Here, we report the generation of the first dual reporter mouse embryonic stem cell (mESC) lines designed to facilitate the study of vascular endothelial and smooth muscle development in vitro. These mESC lines express green fluorescent protein (GFP) under the endothelial promoter, Tie-2, and Discomsoma sp. red fluorescent protein (RFP) under the promoter for alpha-smooth muscle actin (α-SMA). The lines were then characterized for morphology, marker expression, and pluripotency. The mESC colonies were found to exhibit dome-shaped morphology, alkaline phosphotase activity, as well as expression of Oct 3/4 and stage-specific embryonic antigen-1. The mESC colonies were also found to display normal karyotypes and are able to generate cells from all three germ layers, verifying pluripotency. Tissue staining confirmed the coexpression of VE (vascular endothelial)-cadherin with the Tie-2 GFP+ expression on endothelial structures and smooth muscle myosin heavy chain with the α-SMA RFP+ smooth muscle cells. Lastly, it was verified that the developing mESC do express Tie-2 GFP+ and α-SMA RFP+ cells during differentiation and that the GFP+ cells colocalize with the vascular-like structures surrounded by α-SMA-RFP cells. These dual reporter vascular-specific mESC permit visualization and cell tracking of individual endothelial and smooth muscle cells over time and in multiple dimensions, a powerful new tool for studying vascular development in real time.

Vascular cambial sucrose metabolism and growth in loblolly pine (Pinus taeda L.) in relation to transplanting stress

Treesearch

Shi-Jean S. Sung; Paul P. Kormanik; C.C. Black

1993-01-01

Sucrose synthase (SS) was the dominant enzyme of sucrose metabolism in both stem and root vascular cambial zone tissues of nursery-grown loblolly pine (Pinus taeda L.) seedlings.Acid invertase (AI) and neutral invertase (NI) activties were generally less than 10% of the SS activity in both tissues.In both cambial tissues, seasonal patterns of SS activity in stem and...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linde, B.; Hjemdahl, P.; Freyschuss, U.

Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilationmore » in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.« less

In Vitro Vascular Cell Adhesion and Proliferation on Alkaline Degraded Poly-lactic/glycolic Acid Polymers

DTIC Science & Technology

2002-04-01

implanted gr~itf often leads to intimal hyperplasia which has resulted in occlusion of the regenerated vascular tissue [1, 2]. Since an endothelial... fibrovascular tissue ingrowth [I]. Clearly, the inability of poly(lactic acid) containing polymers to promote sufficient endothelialization presents serious

Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture

PubMed Central

Zhu, Wei; Qu, Xin; Zhu, Jie; Ma, Xuanyi; Patel, Sherrina; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Gou, Maling; Xu, Yang; Zhang, Kang; Chen, Shaochen

2017-01-01

Living tissues rely heavily on vascular networks to transport nutrients, oxygen and metabolic waste. However, there still remains a need for a simple and efficient approach to engineer vascularized tissues. Here, we created prevascularized tissues with complex three-dimensional (3D) microarchitectures using a rapid bioprinting method – microscale continuous optical bioprinting (μCOB). Multiple cell types mimicking the native vascular cell composition were encapsulated directly into hydrogels with precisely controlled distribution without the need of sacrificial materials or perfusion. With regionally controlled biomaterial properties the endothelial cells formed lumen-like structures spontaneously in vitro. In vivo implantation demonstrated the survival and progressive formation of the endothelial network in the prevascularized tissue. Anastomosis between the bioprinted endothelial network and host circulation was observed with functional blood vessels featuring red blood cells. With the superior bioprinting speed, flexibility and scalability, this new prevascularization approach can be broadly applicable to the engineering and translation of various functional tissues. PMID:28192772

Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture.

PubMed

Zhu, Wei; Qu, Xin; Zhu, Jie; Ma, Xuanyi; Patel, Sherrina; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Gou, Maling; Xu, Yang; Zhang, Kang; Chen, Shaochen

2017-04-01

Living tissues rely heavily on vascular networks to transport nutrients, oxygen and metabolic waste. However, there still remains a need for a simple and efficient approach to engineer vascularized tissues. Here, we created prevascularized tissues with complex three-dimensional (3D) microarchitectures using a rapid bioprinting method - microscale continuous optical bioprinting (μCOB). Multiple cell types mimicking the native vascular cell composition were encapsulated directly into hydrogels with precisely controlled distribution without the need of sacrificial materials or perfusion. With regionally controlled biomaterial properties the endothelial cells formed lumen-like structures spontaneously in vitro. In vivo implantation demonstrated the survival and progressive formation of the endothelial network in the prevascularized tissue. Anastomosis between the bioprinted endothelial network and host circulation was observed with functional blood vessels featuring red blood cells. With the superior bioprinting speed, flexibility and scalability, this new prevascularization approach can be broadly applicable to the engineering and translation of various functional tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Development of elastameric sealant designed for arterial field].

PubMed

Matsuda, Takehisa; Nakajima, Nobuyuki

2013-04-01

The development of a reliable surgical sealant specific for arterial tissues has been long awaited. In this article, first the "ideal" adhesion mechanism formulated from biomechanical concept is proposed for ensured hemostasis in dissected arteries with pulsatile flow. An urethane prepolymer prepared along the design criteria is viscous liquid. Due to its high water absorbility and high reactivity with water, the sealant applied to vascular tissues becomes an elastomer within several minutes. When the sealant was applied to dissected canine abdominal arteries with 3 stay sutures, followed by declamping 5 minutes, neither bleeding nor detrimental effect on tissue morphogenesis was observed. This sealant is being ready to the market.

Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

PubMed

Temple, Joshua P; Hutton, Daphne L; Hung, Ben P; Huri, Pinar Yilgor; Cook, Colin A; Kondragunta, Renu; Jia, Xiaofeng; Grayson, Warren L

2014-12-01

The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts. © 2014 Wiley Periodicals, Inc.

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

PubMed Central

Di Pietro, Marisa; Filardo, Simone; De Santis, Fiorenzo; Sessa, Rosa

2013-01-01

Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development. PMID:23877837

Non-invasive optical modulation of local vascular permeability

NASA Astrophysics Data System (ADS)

Choi, Myunghwan; Choi, Chulhee

2011-03-01

For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight.

PubMed

Tahimic, Candice G T; Globus, Ruth K

2017-10-16

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI.

PubMed

Digernes, Ingrid; Bjørnerud, Atle; Vatnehol, Svein Are S; Løvland, Grete; Courivaud, Frédéric; Vik-Mo, Einar; Meling, Torstein R; Emblem, Kyrre E

2017-06-01

Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.

VESGEN Software for Mapping and Quantification of Vascular Regulators

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

2012-01-01

VESsel GENeration (VESGEN) Analysis is an automated software that maps and quantifies effects of vascular regulators on vascular morphology by analyzing important vessel parameters. Quantification parameters include vessel diameter, length, branch points, density, and fractal dimension. For vascular trees, measurements are reported as dependent functions of vessel branching generation. VESGEN maps and quantifies vascular morphological events according to fractal-based vascular branching generation. It also relies on careful imaging of branching and networked vascular form. It was developed as a plug-in for ImageJ (National Institutes of Health, USA). VESGEN uses image-processing concepts of 8-neighbor pixel connectivity, skeleton, and distance map to analyze 2D, black-and-white (binary) images of vascular trees, networks, and tree-network composites. VESGEN maps typically 5 to 12 (or more) generations of vascular branching, starting from a single parent vessel. These generations are tracked and measured for critical vascular parameters that include vessel diameter, length, density and number, and tortuosity per branching generation. The effects of vascular therapeutics and regulators on vascular morphology and branching tested in human clinical or laboratory animal experimental studies are quantified by comparing vascular parameters with control groups. VESGEN provides a user interface to both guide and allow control over the users vascular analysis process. An option is provided to select a morphological tissue type of vascular trees, network or tree-network composites, which determines the general collections of algorithms, intermediate images, and output images and measurements that will be produced.

A new fundamental bioheat equation for muscle tissue--part II: Temperature of SAV vessels.

PubMed

Zhu, Liang; Xu, Lisa X; He, Qinghong; Weinbaum, Sheldon

2002-02-01

In this study, a new theoretical framework was developed to investigate temperature variations along countercurrent SAV blood vessels from 300 to 1000 microm diameter in skeletal muscle. Vessels of this size lie outside the range of validity of the Weinbaum-Jiji bioheat equation and, heretofore, have been treated using discrete numerical methods. A new tissue cylinder surrounding these vessel pairs is defined based on vascular anatomy, Murray's law, and the assumption of uniform perfusion. The thermal interaction between the blood vessel pair and surrounding tissue is investigated for two vascular branching patterns, pure branching and pure perfusion. It is shown that temperature variations along these large vessel pairs strongly depend on the branching pattern and the local blood perfusion rate. The arterial supply temperature in different vessel generations was evaluated to estimate the arterial inlet temperature in the modified perfusion source term for the s vessels in Part I of this study. In addition, results from the current research enable one to explore the relative contribution of the SAV vessels and the s vessels to the overall thermal equilibration between blood and tissue.

Microengineering in cardiovascular research: new developments and translational applications.

PubMed

Chan, Juliana M; Wong, Keith H K; Richards, Arthur Mark; Drum, Chester L

2015-04-01

Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease. In recent years, advances in technical fabrication and biological integration have provided new insights into biological phenomena, improved diagnostic measurements, and made major steps towards de novo tissue creation. Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics. With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Potential applications of cutin-derived CuO reaction products for discriminating vascular plant sources in natural environments

NASA Astrophysics Data System (ADS)

Goñi, Miguel A.; Hedges, John I.

1990-11-01

An extensive suite of C 14-C 18 hydroxylated fatty acids of cutin origin was identified among the nonlignin CuO reaction products from tissues of 67 different plant species. These mid-chain and ω-hydroxylated cutin acids together accounted for 0.5 to 4% of the organic carbon (OC) in these nonwoody vascular plant tissues and were produced in characteristically different yields by the various plant types. Nonvascular plants, including bulk phytoplankton, kelps, mosses, and liverworts, did not yield measurable amounts of cutin acids, except for trace levels of ω-hydroxytetradecanoic acid detected in kelps. Most of the "lower" vascular plants, such as clubmosses and ferns, produced simple cutin acid suites composed mainly of ω-hydroxy C 14 and C 16 acids. Gymnosperm needles yielded cutin acid suites dominated by C 16 acids, in which 9,16- and 10,16-dihydroxyhexadecanoic acids were characteristically abundant. Relatively high yields of C 18 acids were obtained from angiosperm tissues, among which dicotyledons exhibited a predominance of 9,10,18-trihydroxyoctadecanoic acid over all the other C 18 acids. The Chromatographie peak corresponding to dihydroxyhexadecanoic acid was a mixture of the positional isomers 8,16-, 9, 16-, and 10,16-dihydroxyhexadecanoic acids, whose relative abundances uniquely characterized monocotyledon tissues and distinguished among different types of gymnosperm tissues. Based on the cutin acid yields obtained from the different plant types, several geochemical parameters were developed to distinguish up to six different cutin-bearing plant groups as possible components of sedimentary mixtures.

Morphological analysis of lymph nodes in Odontocetes from north and northeast coast of Brazil.

PubMed

De Oliveira e Silva, Fernanda Menezes; Guimarães, Juliana Plácido; Vergara-Parente, Jociery Einhardt; Carvalho, Vitor Luz; De Meirelles, Ana Carolina Oliveira; Marmontel, Miriam; Ferrão, Juliana Shimara Pires; Miglino, Maria Angelica

2014-05-01

The morphology and location of lymph nodes from seven species of Odontocetes, of both sexes and different age groups, were described. All animals were derived from stranding events along the North and Northeastern coasts of Brazil. After the identification of lymph nodes in situ, tissue samples were analyzed for light and electron microscopy. Vascular volume density (VVD) and vascular length density (VLD) were evaluated in the mesenteric lymph nodes. Lymph nodes occurred as solitary nodules or in groups, varying in shape and size. In addition to using the nomenclature recommended by Nomina Anatomica Veterinaria, new nomenclatures were suggested based on the lymph nodes topography. Lymph nodes were covered by a highly vascularized and innervated capsule of dense connective tissue, below which muscle fibers were observed, inconsistently, in all studied species. There was no difference in VLD among different age groups. However, VVD was higher in adults. Lymph nodes parenchyma was divided into an outer cortex, containing lymph nodules and germinal centers; a paracortical region, transition zone with dense lymphoid tissue; and an inner medulla, composed of small irregular cords of lymphatic tissue, blood vessels, and diffuse lymphoid tissue. Abundant collagen fibers were observed around arteries and arterioles. Germinal centers were more evident and developed in calves and young animals, being more discrete and sparse in adults. The morphology of lymph nodes in Odontocetes was typical of that observed in other terrestrial mammals. However, new groups of lymph nodes were described for seven species occurring in the Brazilian coast. Copyright © 2014 Wiley Periodicals, Inc.

Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

PubMed

Maessen, Dionne E; Brouwers, Olaf; Gaens, Katrien H; Wouters, Kristiaan; Cleutjens, Jack P; Janssen, Ben J; Miyata, Toshio; Stehouwer, Coen D; Schalkwijk, Casper G

2016-04-01

Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Biomechanics and functional morphology of a climbing monocot

PubMed Central

Hesse, Linnea; Wagner, Sarah T.; Neinhuis, Christoph

2016-01-01

Plants with a climbing growth habit possess unique biomechanical properties arising from adaptations to changing loading conditions connected with close attachment to mechanical supports. In monocot climbers, mechanical adaptation is restricted by the absence of a bifacial vascular cambium. Flagellaria indica was used to investigate the mechanical properties and adaptations of a monocot climber that, uniquely, attaches to the surrounding vegetation via leaf tendrils. Biomechanical methods such as three-point bending and torsion tests were used together with anatomical studies on tissue development, modification and distribution. In general, the torsional modulus was lower than the bending modulus; hence, torsional stiffness was less than flexural stiffness. Basal parts of mature stems showed the greatest stiffness while that of more apical stem segments levelled off. Mechanical properties were modulated via tissue maturation processes mainly affecting the peripheral region of the stem. Peripheral vascular bundles showed a reduction in the amount of conducting tissue while the proportion and density of the bundle sheath increased. Furthermore, adjacent bundle sheaths merged resulting in a dense ring of fibrous tissue. Although F. indica lacks secondary cambial growth, the climbing habit is facilitated by a complex interaction of tissue maturation and attachment. PMID:26819259

A cross-circulated bicephalic model of head transplantation.

PubMed

Li, Peng-Wei; Zhao, Xin; Zhao, Yun-Long; Wang, Bing-Jian; Song, Yang; Shen, Zi-Long; Jiang, Hong-Jun; Jin, Hai; Canavero, Sergio; Ren, Xiao-Ping

2017-06-01

A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. The thoracic aorta and superior vena cava of a donor rat were anastomosed with the carotid artery and extracorporeal veins of a recipient rat by vascular grafts. Before thoracotomy in the donor rat, the axillary artery and vein of the donor were connected to the carotid and the extracranial vein of the third rat through a silicone tube. The silicone tube was passed through a peristaltic pump to ensure donor brain tissue blood supply. There is no ischemia reperfusion injury in donor brain tissue analyzed by electroencephalogram. Postoperative donor has pain reflex and corneal reflex. Peristaltic pump application can guarantee the blood supply of donor brain tissue per unit time, while the application of temperature change device to the silicone tube can protect the brain tissue hypothermia, postoperative experimental data show that there is no brain tissue ischemia during the whole operation. The application of vascular grafting can also provide the possibility of long-term survival of the model. © 2017 John Wiley & Sons Ltd.

Cryopreservation of human vascular umbilical cord cells under good manufacturing practice conditions for future cell banks.

PubMed

Polchow, Bianca; Kebbel, Kati; Schmiedeknecht, Gerno; Reichardt, Anne; Henrich, Wolfgang; Hetzer, Roland; Lueders, Cora

2012-05-16

In vitro fabricated tissue engineered vascular constructs could provide an alternative to conventional substitutes. A crucial factor for tissue engineering of vascular constructs is an appropriate cell source. Vascular cells from the human umbilical cord can be directly isolated and cryopreserved until needed. Currently no cell bank for human vascular cells is available. Therefore, the establishment of a future human vascular cell bank conforming to good manufacturing practice (GMP) conditions is desirable for therapeutic applications such as tissue engineered cardiovascular constructs. A fundamental step was the adaption of conventional research and development starting materials to GMP compliant starting materials. Human umbilical cord artery derived cells (HUCAC) and human umbilical vein endothelial cells (HUVEC) were isolated, cultivated, cryopreserved (short- and long-term) directly after primary culture and recultivated subsequently. Cell viability, expression of cellular markers and proliferation potential of fresh and cryopreserved cells were studied using trypan blue staining, flow cytometry analysis, immunofluorescence staining and proliferation assays. Statistical analyses were performed using Student's t-test. Sufficient numbers of isolated cells with acceptable viabilities and homogenous expression of cellular markers confirmed that the isolation procedure was successful using GMP compliant starting materials. The influence of cryopreservation was marginal, because cryopreserved cells mostly maintain phenotypic and functional characteristics similar to those of fresh cells. Phenotypic studies revealed that fresh cultivated and cryopreserved HUCAC were positive for alpha smooth muscle actin, CD90, CD105, CD73, CD29, CD44, CD166 and negative for smoothelin. HUVEC expressed CD31, CD146, CD105 and CD144 but not alpha smooth muscle actin. Functional analysis demonstrated acceptable viability and sufficient proliferation properties of cryopreserved HUCAC and HUVEC. Adaptation of cell isolation, cultivation and cryopreservation to GMP compliant starting materials was successful. Cryopreservation did not influence cell properties with lasting impact, confirming that the application of vascular cells from the human umbilical cord is feasible for cell banking. A specific cellular marker expression profile was established for HUCAC and HUVEC using flow cytometry analysis, applicable as a GMP compliant quality control. Use of these cells for the future fabrication of advanced therapy medicinal products GMP conditions are required by the regulatory authority.

The Resistance of Certain Tissues to Invasion

PubMed Central

Eisenstein, Reuben; Sorgente, Nino; Soble, Lawrence W.; Miller, Alexander; Kuettner, Klaus E.

1973-01-01

If puppy tissues are explanted onto the chick chorioallantoic membrane, those tissues which normally have a blood supply are rapidly invaded by vascularized mesenchyme of host origin. Hyaline cartilage, a tissue virtually devoid of blood vessels, is impenetrable by proliferating mesenchyme of the host, while calcified cartilage, which normally is vascularized, is penetrable. The stroma of the cornea, another normally avascular tissue, is readily penetrable, but Descemet's membrane forms a barrier to invasion by host tissues. The experimental system used permits the design of experiments in which the study of factors responsible for the resistance of tissues such as cartilage to invasion can be undertaken. ImagesFig 1Fig 2Fig 3Fig 4 PMID:4129060

Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance.

PubMed

Lee, Robert Mkw; Dickhout, Jeffrey G; Sandow, Shaun L

2017-04-01

Essential hypertension is a complex multifactorial disease process that involves the interaction of multiple genes at various loci throughout the genome, and the influence of environmental factors such as diet and lifestyle, to ultimately determine long-term arterial pressure. These factors converge with physiological signaling pathways to regulate the set-point of long-term blood pressure. In hypertension, structural changes in arteries occur and show differences within and between vascular beds, between species, models and sexes. Such changes can also reflect the development of hypertension, and the levels of circulating humoral and vasoactive compounds. The role of perivascular adipose tissue in the modulation of vascular structure under various disease states such as hypertension, obesity and metabolic syndrome is an emerging area of research, and is likely to contribute to the heterogeneity described in this review. Diversity in structure and related function is the norm, with morphological changes being causative in some beds and states, and in others, a consequence of hypertension. Specific animal models of hypertension have advantages and limitations, each with factors influencing the relevance of the model to the human hypertensive state/s. However, understanding the fundamental properties of artery function and how these relate to signalling mechanisms in real (intact) tissues is key for translating isolated cell and model data to have an impact and relevance in human disease etiology. Indeed, the ultimate aim of developing new treatments to correct vascular dysfunction requires understanding and recognition of the limitations of the methodologies used.

Hollow fibers of poly(lactide-co-glycolide) and poly(ε-caprolactone) blends for vascular tissue engineering applications.

PubMed

Diban, Nazely; Haimi, Suvi; Bolhuis-Versteeg, Lydia; Teixeira, Sandra; Miettinen, Susanna; Poot, André; Grijpma, Dirk; Stamatialis, Dimitrios

2013-05-01

At present the manufacture of small-diameter blood vessels is one of the main challenges in the field of vascular tissue engineering. Currently available vascular grafts rapidly fail due to development of intimal hyperplasia and thrombus formation. Poly(lactic-co-glycolic acid) (PLGA) hollow fiber (HF) membranes have previously been proposed for this application, but as we show in the present work, they have an inhibiting effect on cell proliferation and rather poor mechanical properties. To overcome this we prepared HF membranes via phase inversion using blends of PLGA with poly(ε-caprolactone) (PCL). The influence of polymer composition on the HF physicochemical properties (topography, water transport and mechanical properties) and cell attachment and proliferation were studied. Our results show that only the ratio PCL/PLGA of 85/15 (PCL/PLGA85/15) yielded a miscible blend after processing. A higher PLGA concentration in the blend led to immiscible PCL/PLGA phase-separated HFs with an inhomogeneous morphology and variation in the cell culture results. In fact, the PCL/PLGA85/15 blend, which had the most homogeneous morphology and suitable pore structure, showed better human adipose stem cell (hASC) attachment and proliferation compared with the homopolymers. This, combined with the good mechanical and transport properties, makes them potentially useful for the development of small-caliber vascular grafts. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Artery cross-clamping during laparoscopic vascular surgeries; a computational tactile sensing approach.

PubMed

Pahlavan, Pedram; Najarian, Siamak; Afshari, Elnaz; Moini, Majid

2013-01-01

Artificial palpation is one of the most valuable achievements of artificial tactile sensing approach that can be used in various fields of medicine and more specifically in surgery. These techniques cause different surgical maneuvers to be done more precisely and noninvasively. In this study, considering the present problems and limitations of cross-clamping an artery during laparoscopic vascular surgeries, a new tactile sensory system will be introduced.Having imitated surgeon's palpation during open vascular surgeries and modeled it conceptually, the optimal amount of the total angular displacement of each robot joint in order to cross-clamping an artery without damaging to the artery surrounding tissues will be calculated. The elastic governing equation of contact occurred between the tactile sensor placed on the first link of the robot and the surrounding tissues around the artery were developed. A finite element model is coupled with genetic algorithm optimization method so that the normal stress and displacements in contact surface of the robot and artery's surrounding tissues would be minimized. Thus, reliability and accuracy of artificial tactile sensing method in artery cross-clamping will be demonstrated. Finally, the functional principles of the new tactile system capable of cross-clamping an artery during laparoscopic surgeries will be presented.

Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering

PubMed Central

Irastorza, Ramiro M.; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

2015-01-01

Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model. PMID:25834840

Mathematical modeling of uniaxial mechanical properties of collagen gel scaffolds for vascular tissue engineering.

PubMed

Irastorza, Ramiro M; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

2015-01-01

Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

The Role of Adenosine A2A Receptor, CYP450s, and PPARs in the Regulation of Vascular Tone

PubMed Central

Khayat, Maan T.

2017-01-01

Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors, A2A receptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), and KATP channels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases. PMID:28884118

Adipose tissue-derived stem cells enhance bioprosthetic mesh repair of ventral hernias.

PubMed

Altman, Andrew M; Abdul Khalek, Feras J; Alt, Eckhard U; Butler, Charles E

2010-09-01

Bioprosthetic mesh used for ventral hernia repair becomes incorporated into the musculofascial edge by cellular infiltration and vascularization. Adipose tissue-derived stem cells promote tissue repair and vascularization and may increase the rate or degree of tissue incorporation. The authors hypothesized that introducing these cells into bioprosthetic mesh would result in adipose tissue-derived stem cell engraftment and proliferation and enhance incorporation of the bioprosthetic mesh. Adipose tissue-derived stem cells were isolated from the subcutaneous adipose tissue of syngeneic Brown Norway rats, expanded in vitro, and labeled with green fluorescent protein. Thirty-six additional rats underwent inlay ventral hernia repair with porcine acellular dermal matrix. Two 12-rat groups had the cells (1.0 x 10(6)) injected directly into the musculofascial/porcine acellular dermal matrix interface after repair or received porcine acellular dermal matrix on which the cells had been preseeded; the 12-rat control group received no stem cells. At 2 weeks, adipose tissue-derived stem cells in both stem cell groups engrafted, survived, migrated, and proliferated. Mean cellular infiltration into porcine acellular dermal matrix at the musculofascial/graft interface was significantly greater in the preseeded and injected stem cell groups than in the control group. Mean vascular infiltration of the porcine acellular dermal matrix was significantly greater in both stem cell groups than in the control group. Preseeded and injected adipose tissue-derived stem cells engraft, migrate, proliferate, and enhance the vascularity of porcine acellular dermal matrix grafts at the musculofascial/graft interface. These cells can thus enhance incorporation of porcine acellular dermal matrix into the abdominal wall after repair of ventral hernias.

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

PubMed

Qi, Dianjun; Wu, Shaohua; Kuss, Mitchell A; Shi, Wen; Chung, Soonkyu; Deegan, Paul T; Kamenskiy, Alexey; He, Yini; Duan, Bin

2018-05-26

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic differentiation and maturation of human adipose progenitor cells and adipose derived mesenchymal stromal cells. Moreover, the cryogels also supported 3D bioprinting on top, forming vascularized adipose constructs. This study demonstrates the potential of the implementation of cryogels for generating volume-stable adipose tissue constructs and provides a strategy to fabricate vascularized flap-like constructs for complex soft tissue regeneration. Copyright © 2018. Published by Elsevier Ltd.

Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival.

PubMed

Schipani, E; Ryan, H E; Didrickson, S; Kobayashi, T; Knight, M; Johnson, R S

2001-11-01

Breakdown or absence of vascular oxygen delivery is a hallmark of many common human diseases, including cancer, myocardial infarction, and stroke. The chief mediator of hypoxic response in mammalian tissues is the transcription factor hypoxia-inducible factor 1 (HIF-1), and its oxygen-sensitive component HIF-1alpha. A key question surrounding HIF-1alpha and the hypoxic response is the role of this transcription factor in cells removed from a functional vascular bed; in this regard there is evidence indicating that it can act as either a survival factor or induce growth arrest and apoptosis. To study more closely how HIF-1alpha functions in hypoxia in vivo, we used tissue-specific targeting to delete HIF-1alpha in an avascular tissue: the cartilaginous growth plate of developing bone. We show here the first evidence that the developmental growth plate in mammals is hypoxic, and that this hypoxia occurs in its interior rather than at its periphery. As a result of this developmental hypoxia, cells that lack HIF-1alpha in the interior of the growth plate die. This is coupled to decreased expression of the CDK inhibitor p57, and increased levels of BrdU incorporation in HIF-1alpha null growth plates, indicating defects in HIF-1alpha-regulated growth arrest occurs in these animals. Furthermore, we find that VEGF expression in the growth plate is regulated through both HIF-1alpha-dependent and -independent mechanisms. In particular, we provide evidence that VEGF expression is up-regulated in a HIF-1alpha-independent manner in chondrocytes surrounding areas of cell death, and this in turn induces ectopic angiogenesis. Altogether, our findings have important implications for the role of hypoxic response and HIF-1alpha in development, and in cell survival in tissues challenged by interruption of vascular flow; they also illustrate the complexities of HIF-1alpha response in vivo, and they provide new insights into mechanisms of growth plate development.

Structural development of wheat nutrient transfer tissues and their relationships with filial tissues development.

PubMed

Xurun, Yu; Xinyu, Chen; Liang, Zhou; Jing, Zhang; Heng, Yu; Shanshan, Shao; Fei, Xiong; Zhong, Wang

2015-03-01

Nutrients from spikelet phloem are commonly delivered to endosperm via caryopsis nutrient transfer tissues (NTTs). Elucidation of NTTs development is paramount to developing an understanding of the control of assimilate partitioning. Little information was available on the structural development of the entire NTTs and their functions, particularly those involved in the relationship between development of NTTs and growth of filial tissues including endosperm and embryo. In this study, wheat caryopses at different development stages were collected for observation of the NTTs by light microscopy, stereoscopic microscopy, and scanning electron microscopy. The cytological features of NTTs in the developing wheat caryopsis were clearly elucidated. The results were as follows: NTTs in the wheat caryopsis include maternal transfer tissues that are composed of vascular bundle, chalaza and nucellar projection transfer cells, and endosperm transfer tissues that consist of the aleurone transfer cells, starchy endosperm transfer cells, and endosperm conducting cells. The initiation, development, and apoptosis of these NTTs revealed the pattern of temporal and spatial gradient and were closely coordinated with endosperm and embryo development. These results may give us a further understanding about the functions of NTTs and their relationships with endosperm and embryo development.

Tumors: wounds that do not heal-redux.

PubMed

Dvorak, Harold F

2015-01-01

Similarities between tumors and the inflammatory response associated with wound healing have been recognized for more than 150 years and continue to intrigue. Some years ago, based on our then recent discovery of vascular permeability factor (VPF)/VEGF, I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound-healing response to induce the stroma they required for maintenance and growth. Work over the past few decades has supported this hypothesis and has put it on a firmer molecular basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and wounds that includes the following: increased vascular permeability; extravasation of plasma, fibrinogen and other plasma proteins; activation of the clotting system outside the vascular system; deposition of an extravascular fibrin gel that serves as a provisional stroma and a favorable matrix for cell migration; induction of angiogenesis and arterio-venogenesis; subsequent degradation of fibrin and its replacement by "granulation tissue" (highly vascular connective tissue); and, finally, vascular resorption and collagen synthesis, resulting in the formation of dense fibrous connective tissue (called "scar tissue" in wounds and "desmoplasia" in cancer). A similar sequence of events also takes place in a variety of important inflammatory diseases that involve cellular immunity. ©2015 American Association for Cancer Research.

Blood Flow Modulation of Vascular Dynamics

PubMed Central

Lee, Juhyun; Sevag Packard, René R.; Hsiai, Tzung K.

2015-01-01

Purpose of review Blood flow is intimately linked with cardiovascular development, repair, and dysfunction. The current review will build on the fluid mechanical principle underlying hemodynamic shear forces, mechanotransduction, and metabolic effects. Recent findings Pulsatile flow produces both time- (∂τ /∂t)and spatial-varying shear stress (∂τ /∂x) to modulate vascular oxidative stress and inflammatory response with pathophysiological significance to atherosclerosis. The characteristics of hemodynamic shear forces; namely, steady laminar (∂τ /∂t= 0), pulsatile (PSS: unidirectional forward flow), and oscillatory shear stress (OSS: bidirectional with a near net 0 forward flow) modulate mechano-signal transduction to influence metabolic effects on vascular endothelial function. Atheroprotective PSS promotes anti-oxidant, anti-inflammatory, and anti-thrombotic responses, whereas atherogenic OSS induces NADPH oxidase–JNK signaling to increase mitochondrial superoxide production, protein degradation of manganese superoxide dismutase (MnSOD), and post-translational protein modifications of LDL particles in the disturbed flow-exposed regions of vasculature. In the era of tissue regeneration, shear stress has been implicated in re-activation of developmental genes; namely, Wnt and Notch signaling, for vascular development and repair. Summary Blood flow imparts a dynamic continuum from vascular development to repair. Augmentation of PSS confers atheroprotection and re-activation of developmental signaling pathways for regeneration. PMID:26218416

Dynamic Analysis of Vascular Morphogenesis Using Transgenic Quail Embryos

PubMed Central

Huss, David; Filla, Michael B.; Czirok, Andras; Rongish, Brenda J.; Little, Charles D.; Fraser, Scott E.; Lansford, Rusty

2010-01-01

Background One of the least understood and most central questions confronting biologists is how initially simple clusters or sheet-like cell collectives can assemble into highly complex three-dimensional functional tissues and organs. Due to the limits of oxygen diffusion, blood vessels are an essential and ubiquitous presence in all amniote tissues and organs. Vasculogenesis, the de novo self-assembly of endothelial cell (EC) precursors into endothelial tubes, is the first step in blood vessel formation [1]. Static imaging and in vitro models are wholly inadequate to capture many aspects of vascular pattern formation in vivo, because vasculogenesis involves dynamic changes of the endothelial cells and of the forming blood vessels, in an embryo that is changing size and shape. Methodology/Principal Findings We have generated Tie1 transgenic quail lines Tg(tie1:H2B-eYFP) that express H2B-eYFP in all of their endothelial cells which permit investigations into early embryonic vascular morphogenesis with unprecedented clarity and insight. By combining the power of molecular genetics with the elegance of dynamic imaging, we follow the precise patterning of endothelial cells in space and time. We show that during vasculogenesis within the vascular plexus, ECs move independently to form the rudiments of blood vessels, all while collectively moving with gastrulating tissues that flow toward the embryo midline. The aortae are a composite of somatic derived ECs forming its dorsal regions and the splanchnic derived ECs forming its ventral region. The ECs in the dorsal regions of the forming aortae exhibit variable mediolateral motions as they move rostrally; those in more ventral regions show significant lateral-to-medial movement as they course rostrally. Conclusions/Significance The present results offer a powerful approach to the major challenge of studying the relative role(s) of the mechanical, molecular, and cellular mechanisms of vascular development. In past studies, the advantages of the molecular genetic tools available in mouse were counterbalanced by the limited experimental accessibility needed for imaging and perturbation studies. Avian embryos provide the needed accessibility, but few genetic resources. The creation of transgenic quail with labeled endothelia builds upon the important roles that avian embryos have played in previous studies of vascular development. PMID:20856866

A bHLH-Based Feedback Loop Restricts Vascular Cell Proliferation in Plants.

PubMed

Vera-Sirera, Francisco; De Rybel, Bert; Úrbez, Cristina; Kouklas, Evangelos; Pesquera, Marta; Álvarez-Mahecha, Juan Camilo; Minguet, Eugenio G; Tuominen, Hannele; Carbonell, Juan; Borst, Jan Willem; Weijers, Dolf; Blázquez, Miguel A

2015-11-23

Control of tissue dimensions in multicellular organisms requires the precise quantitative regulation of mitotic activity. In plants, where cells are immobile, tissue size is achieved through control of both cell division orientation and mitotic rate. The bHLH transcription factor heterodimer formed by target of monopteros5 (TMO5) and lonesome highway (LHW) is a central regulator of vascular width-increasing divisions. An important unanswered question is how its activity is limited to specify vascular tissue dimensions. Here we identify a regulatory network that restricts TMO5/LHW activity. We show that thermospermine synthase ACAULIS5 antagonizes TMO5/LHW activity by promoting the accumulation of SAC51-LIKE (SACL) bHLH transcription factors. SACL proteins heterodimerize with LHW-therefore likely competing with TMO5/LHW interactions-prevent activation of TMO5/LHW target genes, and suppress the over-proliferation caused by excess TMO5/LHW activity. These findings connect two thus-far disparate pathways and provide a mechanistic understanding of the quantitative control of vascular tissue growth. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined flaps based on the superficial temporal vascular system for reconstruction of facial defects.

PubMed

Zhou, Renpeng; Wang, Chen; Qian, Yunliang; Wang, Danru

2015-09-01

Facial defects are multicomponent deficiencies rather than simple soft-tissue defects. Based on different branches of the superficial temporal vascular system, various tissue components can be obtained to reconstruct facial defects individually. From January 2004 to December 2013, 31 patients underwent reconstruction of facial defects with composite flaps based on the superficial temporal vascular system. Twenty cases of nasal defects were repaired with skin and cartilage components, six cases of facial defects were treated with double island flaps of the skin and fascia, three patients underwent eyebrow and lower eyelid reconstruction with hairy and hairless flaps simultaneously, and two patients underwent soft-tissue repair with auricular combined flaps and cranial bone grafts. All flaps survived completely. Donor-site morbidity is minimal, closed primarily. Donor areas healed with acceptable cosmetic results. The final outcome was satisfactory. Combined flaps based on the superficial temporal vascular system are a useful and versatile option in facial soft-tissue reconstruction. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Arabidopsis thickvein mutation affects vein thickness and organ vascularization, and resides in a provascular cell-specific spermine synthase involved in vein definition and in polar auxin transport.

PubMed

Clay, Nicole K; Nelson, Timothy

2005-06-01

Polar auxin transport has been implicated in the induction of vascular tissue and in the definition of vein positions. Leaves treated with chemical inhibitors of polar auxin transport exhibited vascular phenotypes that include increased vein thickness and vascularization. We describe a recessive mutant, thickvein (tkv), which develops thicker veins in leaves and in inflorescence stems. The increased vein thickness is attributable to an increased number of vascular cells. Mutant plants have smaller leaves and shorter inflorescence stems, and this reduction in organ size and height is accompanied by an increase in organ vascularization, which appears to be attributable to an increase in the recruitment of cells into veins. Furthermore, although floral development is normal, auxin transport in the inflorescence stem is significantly reduced in the mutant, suggesting that the defect in auxin transport is responsible for the vascular phenotypes. In the primary root, the veins appear morphologically normal, but root growth in the tkv mutant is hypersensitive to exogenous cytokinin. The tkv mutation was found to reside in the ACL5 gene, which encodes a spermine synthase and whose expression is specific to provascular cells. We propose that ACL5/TKV is involved in vein definition (defining the boundaries between veins and nonvein regions) and in polar auxin transport, and that polyamines are involved in this process.

Arabidopsis thickvein Mutation Affects Vein Thickness and Organ Vascularization, and Resides in a Provascular Cell-Specific Spermine Synthase Involved in Vein Definition and in Polar Auxin Transport1

PubMed Central

Clay, Nicole K.; Nelson, Timothy

2005-01-01

Polar auxin transport has been implicated in the induction of vascular tissue and in the definition of vein positions. Leaves treated with chemical inhibitors of polar auxin transport exhibited vascular phenotypes that include increased vein thickness and vascularization. We describe a recessive mutant, thickvein (tkv), which develops thicker veins in leaves and in inflorescence stems. The increased vein thickness is attributable to an increased number of vascular cells. Mutant plants have smaller leaves and shorter inflorescence stems, and this reduction in organ size and height is accompanied by an increase in organ vascularization, which appears to be attributable to an increase in the recruitment of cells into veins. Furthermore, although floral development is normal, auxin transport in the inflorescence stem is significantly reduced in the mutant, suggesting that the defect in auxin transport is responsible for the vascular phenotypes. In the primary root, the veins appear morphologically normal, but root growth in the tkv mutant is hypersensitive to exogenous cytokinin. The tkv mutation was found to reside in the ACL5 gene, which encodes a spermine synthase and whose expression is specific to provascular cells. We propose that ACL5/TKV is involved in vein definition (defining the boundaries between veins and nonvein regions) and in polar auxin transport, and that polyamines are involved in this process. PMID:15894745

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

PubMed Central

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

A Mutant Receptor Tyrosine Phosphatase, CD148, Causes Defects in Vascular Development

PubMed Central

Takahashi, Takamune; Takahashi, Keiko; St. John, Patricia L.; Fleming, Paul A.; Tomemori, Takuya; Watanabe, Toshio; Abrahamson, Dale R.; Drake, Christopher J.; Shirasawa, Takuji; Daniel, Thomas O.

2003-01-01

Vascularization defects in genetic recombinant mice have defined critical roles for a number of specific receptor tyrosine kinases. Here we evaluated whether an endothelium-expressed receptor tyrosine phosphatase, CD148 (DEP-1/PTPη), participates in developmental vascularization. A mutant allele, CD148ΔCyGFP, was constructed to eliminate CD148 phosphatase activity by in-frame replacement of cytoplasmic sequences with enhanced green fluorescent protein sequences. Homozygous mutant mice died at midgestation, before embryonic day 11.5 (E11.5), with vascularization failure marked by growth retardation and disorganized vascular structures. Structural abnormalities were observed as early as E8.25 in the yolk sac, prior to the appearance of intraembryonic defects. Homozygous mutant mice displayed enlarged vessels comprised of endothelial cells expressing markers of early differentiation, including VEGFR2 (Flk1), Tal1/SCL, CD31, ephrin-B2, and Tie2, with notable lack of endoglin expression. Increased endothelial cell numbers and mitotic activity indices were demonstrated. At E9.5, homozygous mutant embryos showed homogeneously enlarged primitive vessels defective in vascular remodeling and branching, with impaired pericyte investment adjacent to endothelial structures, in similarity to endoglin-deficient embryos. Developing cardiac tissues showed expanded endocardial projections accompanied by defective endocardial cushion formation. These findings implicate a member of the receptor tyrosine phosphatase family, CD148, in developmental vascular organization and provide evidence that it regulates endothelial proliferation and endothelium-pericyte interactions. PMID:12588999

Contribution of endothelial cells to organogenesis: a modern reappraisal of an old Aristotelian concept

PubMed Central

Crivellato, E; Nico, B; Ribatti, D

2007-01-01

It is well established that many tissue-derived factors are involved in blood vessel formation, but evidence is now emerging that endothelial cells themselves represent a crucial source of instructive signals to non-vascular tissue cells during organ development. Thus, endothelial cell signalling is currently believed to promote fundamental cues for cell fate specification, embryo patterning, organ differentiation and postnatal tissue remodelling. This review article summarizes some of the recent advances in our understanding of the role of endothelial cells as effector cells in organ formation. PMID:17683480

In Vitro Study of Directly Bioprinted Perfusable Vasculature Conduits.

PubMed

Zhang, Yahui; Yu, Yin; Akkouch, Adil; Dababneh, Amer; Dolati, Farzaneh; Ozbolat, Ibrahim T

2015-01-01

The ability to create three dimensional (3D) thick tissues is still a major tissue engineering challenge. It requires the development of a suitable vascular supply for an efficient media exchange. An integrated vasculature network is particularly needed when building thick functional tissues and/or organs with high metabolic activities, such as the heart, liver and pancreas. In this work, human umbilical vein smooth muscle cells (HUVSMCs) were encapsulated in sodium alginate and printed in the form of vasculature conduits using a coaxial deposition system. Detailed investigations were performed to understand the dehydration, swelling and degradation characteristics of printed conduits. In addition, because perfusional, permeable and mechanical properties are unique characteristics of natural blood vessels, for printed conduits these properties were also explored in this work. The results show that cells encapsulated in conduits had good proliferation activities and that their viability increased during prolonged in vitro culture. Deposition of smooth muscle matrix and collagen was observed around the peripheral and luminal surface in long-term cultured cellular vascular conduit through histology studies.

Vascular Corrosion Casting: Review of Advantages and Limitations in the Application of Some Simple Quantitative Methods.

PubMed

Hossler, Fred E.; Douglas, John E.

2001-05-01

Vascular corrosion casting has been used for about 40 years to produce replicas of normal and abnormal vasculature and microvasculature of various tissues and organs that could be viewed at the ultrastructural level. In combination with scanning electron microscopy (SEM), the primary application of corrosion casting has been to describe the morphology and anatomical distribution of blood vessels in these tissues. However, such replicas should also contain quantitative information about that vasculature. This report summarizes some simple quantitative applications of vascular corrosion casting. Casts were prepared by infusing Mercox resin or diluted Mercox resin into the vasculature. Surrounding tissues were removed with KOH, hot water, and formic acid, and the resulting dried casts were observed with routine SEM. The orientation, size, and frequency of vascular endothelial cells were determined from endothelial nuclear imprints on various cast surfaces. Vascular volumes of heart, lung, and avian salt gland were calculated using tissue and resin densities, and weights. Changes in vascular volume and functional capillary density in an experimentally induced emphysema model were estimated from confocal images of casts. Clearly, corrosion casts lend themselves to quantitative analysis. However, because blood vessels differ in their compliances, in their responses to the toxicity of casting resins, and in their response to varying conditions of corrosion casting procedures, it is prudent to use care in interpreting this quantitative data. Some of the applications and limitations of quantitative methodology with corrosion casts are reviewed here.

Proteomic Profiling of Tissue-Engineered Blood Vessel Walls Constructed by Adipose-Derived Stem Cells

PubMed Central

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang

2013-01-01

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels. PMID:22963350

Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

PubMed

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

2013-02-01

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue Engineering.

PubMed

Lau, Skadi; Eicke, Dorothee; Carvalho Oliveira, Marco; Wiegmann, Bettina; Schrimpf, Claudia; Haverich, Axel; Blasczyk, Rainer; Wilhelmi, Mathias; Figueiredo, Constança; Böer, Ulrike

2018-03-01

The limited availability of native vessels suitable for the application as hemodialysis shunts or bypass material demands new strategies in cardiovascular surgery. Tissue-engineered vascular grafts containing autologous cells are considered ideal vessel replacements due to the low risk of rejection. However, endothelial cells (EC), which are central components of natural blood vessels, are difficult to obtain from elderly patients of poor health. Umbilical cord blood represents a promising alternative source for EC, but their allogeneic origin corresponds with the risk of rejection after allotransplantation. To reduce this risk, the human leukocyte antigen class I (HLA I) complex was stably silenced by lentiviral vector-mediated RNA interference (RNAi) in EC from peripheral blood and umbilical cord blood and vein. EC from all three sources were transduced by 93.1% ± 4.8% and effectively, HLA I-silenced by up to 67% compared to nontransduced (NT) cells or transduced with a nonspecific short hairpin RNA, respectively. Silenced EC remained capable to express characteristic endothelial surface markers such as CD31 and vascular endothelial cadherin important for constructing a tight barrier, as well as von Willebrand factor and endothelial nitric oxide synthase important for blood coagulation and vessel tone regulation. Moreover, HLA I-silenced EC were still able to align under unidirectional flow, to take up acetylated low-density lipoprotein, and to form capillary-like tube structures in three-dimensional fibrin gels similar to NT cells. In particular, addition of adipose tissue-derived mesenchymal stem cells significantly improved tube formation capability of HLA I-silenced EC toward long and widely branched vascular networks necessary for prevascularizing vascular grafts. Thus, silencing HLA I by RNAi represents a promising technique to reduce the immunogenic potential of EC from three different sources without interfering with EC-specific morphological and functional properties required for vascular tissue engineering. This extends the spectrum of available cell sources from autologous to allogeneic sources, thereby accelerating the generation of tissue-engineered vascular grafts in acute clinical cases.

Optical coherence tomography based angiography [Invited

PubMed Central

Chen, Chieh-Li; Wang, Ruikang K.

2017-01-01

Optical coherence tomography (OCT)-based angiography (OCTA) provides in vivo, three-dimensional vascular information by the use of flowing red blood cells as intrinsic contrast agents, enabling the visualization of functional vessel networks within microcirculatory tissue beds non-invasively, without a need of dye injection. Because of these attributes, OCTA has been rapidly translated to clinical ophthalmology within a short period of time in the development. Various OCTA algorithms have been developed to detect the functional micro-vasculatures in vivo by utilizing different components of OCT signals, including phase-signal-based OCTA, intensity-signal-based OCTA and complex-signal-based OCTA. All these algorithms have shown, in one way or another, their clinical values in revealing micro-vasculatures in biological tissues in vivo, identifying abnormal vascular networks or vessel impairment zones in retinal and skin pathologies, detecting vessel patterns and angiogenesis in eyes with age-related macular degeneration and in skin and brain with tumors, and monitoring responses to hypoxia in the brain tissue. The purpose of this paper is to provide a technical oriented overview of the OCTA developments and their potential pre-clinical and clinical applications, and to shed some lights on its future perspectives. Because of its clinical translation to ophthalmology, this review intentionally places a slightly more weight on ophthalmic OCT angiography. PMID:28271003

Late Wenlock (middle Silurian) bio-events: Caused by volatile boloid impact/s

NASA Technical Reports Server (NTRS)

Berry, W. B. N.; Wilde, P.

1988-01-01

Late Wenlockian (late mid-Silurian) life is characterized by three significant changes or bioevents: sudden development of massive carbonate reefs after a long interval of limited reef growth; sudden mass mortality among colonial zooplankton, graptolites; and origination of land plants with vascular tissue (Cooksonia). Both marine bioevents are short in duration and occur essentially simultaneously at the end of the Wenlock without any recorded major climatic change from the general global warm climate. These three disparate biologic events may be linked to sudden environmental change that could have resulted from sudden infusion of a massive amount of ammonia into the tropical ocean. Impact of a boloid or swarm of extraterrestrial bodies containing substantial quantities of a volatile (ammonia) component could provide such an infusion. Major carbonate precipitation (formation), as seen in the reefs as well as, to a more limited extent, in certain brachiopods, would be favored by increased pH resulting from addition of a massive quantity of ammonia into the upper ocean. Because of the buffer capacity of the ocean and dilution effects, the pH would have returned soon to equilibrium. Major proliferation of massive reefs ceased at the same time. Addition of ammonia as fertilizer to terrestrial environments in the tropics would have created optimum environmental conditions for development of land plants with vascular, nutrient-conductive tissue. Fertilization of terrestrial environments thus seemingly preceded development of vascular tissue by a short time interval. Although no direct evidence of impact of a volatile boloid may be found, the bioevent evidence is suggestive that such an impact in the oceans could have taken place. Indeed, in the case of an ammonia boloid, evidence, such as that of the Late Wenlockian bioevents may be the only available data for impact of such a boloid.

Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature.

PubMed

Maraj, Bharat; Harding-Theobald, Emily; Karaki, Fatima

2018-04-26

Ehlers-Danlos syndrome refers to a spectrum of connective tissue disorders typically caused by mutations in genes responsible for the synthesis of collagen. Patients with Ehlers-Danlos syndrome often exhibit hyperflexibility of joints, increased skin elasticity, and tissue fragility. Vascular Ehlers-Danlos (vEDS) is a subtype of Ehlers-Danlos syndrome with a predilection to involve blood vessels. As such, it often manifests as vascular aneurysms and vessel rupture leading to hemorrhage. There are few reports describing primary prevention of aneurysms in the setting of undiagnosed, suspected vEDS. We present a case of a 30-year-old woman who presents with a pulsatile neck mass found to have multiple arterial aneurysms on imaging, hyperflexibility, and characteristic facial features consistent with vEDS. As described in this case, management of a suspected connective tissue disorder is a multidisciplinary approach including vascular surgery, medical therapy, and genetic testing to confirm the diagnosis. We review literature regarding the care of patients with vascular Ehlers-Danlos as it might pertain to hospitalized patients.

Preventing collapsing of vascular scaffolds: The mechanical behavior of PLA/PCL composite structure prostheses during in vitro degradation.

PubMed

Li, Chaojing; Wang, Fujun; Chen, Peifeng; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-11-01

The success of blood conduit replacement with synthetic graft is highly dependent on the architecture, and mechanical properties of the graft, especially for biodegradable grafts serving as scaffolds for in-situ tissue engineering. Particularly, the property of the radial compression recovery represents a critical to keep the patency during biointegration. Bi-component composite vascular grafts (cVG) made of polylactic acid (PLA) fabric and polycaprolactone (PCL) were developed with superior mechanical properties. In this research, the compressive and tensile properties of the prototypes were characterized when they were subjected to accelerated degradation. In addition, the prepared cVG were analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and wide angle X-ray diffraction (WAXD) to illustrate the gradual loss of mechanical properties. The results demonstrated that the cVG retained the circular cross-section even through its tensile strength decreased during degradation. The cVG samples containing a high percentage of PLA fibers lost their tensile strength faster, while the samples with lower PLA percentage lost the compressive resistance strength more quickly. This unique fabric-based composite biodegradable vascular prosthesis with an outstanding radical compression recovery could be a good candidate for in-situ formation of tissue engineered vascular graft. Copyright © 2017 Elsevier Ltd. All rights reserved.

Surgical hazards posed by marine and freshwater animals in Florida.

PubMed

Howard, R J; Burgess, G H

1993-11-01

Marine and freshwater animals can cause injury to humans by biting, stinging, being poisonous to eat, and causing infections. Biting aquatic animals in Florida include sharks, barracudas, alligators, and moray eels. Devitalized tissue should be débrided, and vascular, neurologic, and tendinous injuries should be repaired. Radiographs should be obtained to examine the injury sit for fractures and retained foreign bodies (teeth). The spines of stingrays and marine catfish can cause soft tissue injury and infection. The spine has a recurved, serrated shape that may cause further injury and break if it is pulled out. The venom may cause local tissue necrosis requiring débridement. Soft tissue infections with marine Vibrio bacteria can occur after eating raw oysters or receiving even minor injuries from marine animals. Thirty-one individuals developed soft tissue infections, 49 developed sepsis, and 23 developed both sepsis and soft tissue infection with marine Vibrio species during a 12-year period. Sixteen patients developed necrotizing soft tissue infections. Treatment is with antibiotics and débridement when necrosis occurs.

Processing highly porous calcium phosphate ceramics for use in bioreactor cores for culturing human liver cells in-vitro

NASA Astrophysics Data System (ADS)

Finoli, Anthony

Chronic liver disease is the 11th highest cause of death in the United States claiming over 30,000 lives in 2009. The current treatment for chronic liver failure is liver transplantation but the availability of tissue is far less than the number of patients in need. To develop human liver tissue in the lab a 3D culturing environment must be created to support the growth of a complex tissue. Hydroxyapatite (HAp) has been chosen as a scaffold material because of its biocompatibility in the body and the ability to create a bioresorbable scaffold. By using a ceramic material, it is possible to create a three dimensional, protective environment in which tissue can grow. The first part of this study is to examine the behavior of adult human liver cells grown on composites of HAp and different biocompatible hydrogels. Porous HAp has been created using an emulsion foaming technique and cells are injected into the structure after being suspended in a hydrogel and are kept in culture for up to 28 days. Functional assays, gene expression and fluorescent microscopy will be used to examine these cultures. The second part of this study will be to develop a processing technique to create a resorbable scaffold that incorporates a vascular system template. Previous experiments have shown the high temperature decomposition of HAp into resorbable calcium phosphates will be used to create a multiphase material. By controlling the amount of transformation product formed, it is proposed that the resorption of the scaffold can be tailored. To introduce a pore network to guide the growth of a vascular system, a positive-negative casting technique has also been developed. A positive polymer copy can be made of a natural vascular system and ceramic is foamed around the copy. During sintering, the polymer is pyrolyzed leaving a multiscale pore network in the ceramic. By combining these techniques, it is proposed that a calcium phosphate bioreactor core can be processed that is suitable for the culturing of human liver tissue.

Control of brown and beige fat development

PubMed Central

Wang, Wenshan; Seale, Patrick

2017-01-01

Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli — notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells and revealed unanticipated cell-lineage relationships between vascular smooth muscle and beige adipocytes, and between brown fat and skeletal muscle cells. Additionally, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells play crucial roles in regulating the differentiation and function of brown and beige fat. PMID:27552974

Myeloid Wnt ligands are required for normal development of dermal lymphatic vasculature.

PubMed

Muley, Ajit; Odaka, Yoshi; Lewkowich, Ian P; Vemaraju, Shruti; Yamaguchi, Terry P; Shawber, Carrie; Dickie, Belinda H; Lang, Richard A

2017-01-01

Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter Wntless we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics. As lymphatic progenitors are emigrating from the cardinal vein and intersomitic vessels, myeloid Wnt ligands regulate both their numbers and migration distance. Later in lymphatic development, myeloid Wnt ligands regulate proliferation of lymphatic endothelial cells (LEC) and thus control lymphatic vessel caliber. Myeloid-specific deletion of WNT co-receptor Lrp5 or Wnt5a gain-of-function also produce elevated caliber in dermal lymphatic capillaries. These data thus suggest that myeloid cells produce Wnt ligands to regulate lymphatic development and use Wnt pathway co-receptors to regulate the balance of Wnt ligand activity during the macrophage-LEC interaction.

Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2015-12-01

response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

Vascular corrosion casting technique steps.

PubMed

Verli, Flaviana Dornela; Rossi-Schneider, Tissiana Raquel; Schneider, Felipe Luís; Yurgel, Liliane Soares; de Souza, Maria Antonieta Lopes

2007-01-01

The vascular corrosion casting technique produces a replica of vascular beds of normal or pathological tissues. Once associated with scanning electron microscopy (SEM), this technique provides details of the three-dimensional anatomic arrangement of the vascular replica, which is the main advantage of this method. The present study is intended to describe the steps of the vascular corrosion casting technique and the different ways to perform them. them.

Advances in the cellular and molecular biology of angiogenesis.

PubMed

Egginton, Stuart; Bicknell, Roy

2011-12-01

Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.

Simultaneous in vivo imaging of diffuse optical reflectance, optoacoustic pressure and ultrasonic scattering (Conference Presentation)

NASA Astrophysics Data System (ADS)

Subochev, Pavel V.; Orlova, Anna G.; Turchin, Ilya V.

2017-03-01

We will present reflection-mode bioimaging system providing complementary optical, photoacsoutic and acoustic measurements by acoustic detector after each laser pulse with 2kHz repetition rate. The photons absorbed within the biological tissue provide optoacoustic (OA) signals, the photons absorbed by the external electrode of a detector provide the measurable diffuse reflectance (DR) from the sample and the probing ultrasonic (US) pulse. To demonstrate the in vivo capabilities of the system we performed complementary DR/OA/US imaging of small laboratory animals and human palm with 3.5mm/50μm/35μm lateral resolution at up to 3 mm diagnostic depth. Functional OA and DR imaging demonstrated the levels of tissue vascularization and blood supply. Structural US imaging was essential for understanding the position of vessels and zones with different perfusion. Before BiOS-2017 we plan to accomplish more in vivo experiments validating the developed triple-modality system as diagnostic tool to detect vascularization as well as mechanisms of vascular changes when monitoring response to therapy.

Does erectile tissue angioarchitecture modify with aging? An immunohistological and morphometric approach.

PubMed

Costa, Carla; Vendeira, Pedro

2008-04-01

Introduction. Erectile dysfunction is a common problem in aged men; however, which vascular cavernosal alterations occur with age progression remain unclarified. Aim. Using cavernosal tissue from rats of various ages, we aimed to thoroughly assess erectile vascular-associated morphologic, immunohistological, and morphometric alterations during aging. Methods. Male Wistar rats were divided according to age in groups of 2, 6, 12, 18, 24 months old (N = 5). Cavernosal tissue of all groups was collected and processed for morphologic evaluation, immunodetection of alpha-smooth muscle actin and von Willebrand factor and morphometric quantification of vascular and smooth muscle cell (SMC) areas. Main Outcome Measures. The morphometric assessment of age-related alterations in cavernosal vascular and SMCs using the ImageJ image-processing program. Results. Morphologic and immunohistological evaluation showed a similar structure of erectile tissue among all age groups, divided in two cavernosal bodies containing numerous sinusoidal vascular spaces surrounded by SMCs. Additionally, we observed a reduction of SMC content and an increase in the caliber of vascular spaces, with aging. This was confirmed by the morphometric quantification of the vascular and SMC areas (mean area x10(3) microm(2) +/- x10(3) standard error). Two-month-old animals had a mean vascular area of 4.21 +/- 0.51, approximately 3.5-fold less than the 6-month-old group. The differences increased when comparing the youngest groups with the 12-, 18-, and 24-month-old animals, with mean measurements of 18.99 +/- 1.91, 25.23 +/- 2.76, and 26.34 +/- 2.97. Conversely, SMC areas progressively decreased between 2- and 6-month-old animals, from 6.75 +/- 0.90 to 6.38 +/- 1.24. The elderly 12-, 18-, and 24-month-old groups presented an approximated 1.5-fold reduction on SMCs area, showed by the respective measurements of 4.11 +/- 0.50, 4.01 +/- 0.35, and 4.02 +/- 0.44. Conclusions. We demonstrated that cavernosal angioarchitecture was modified with aging. The decrease in SMCs and the considerable enlargement of vascular lumens may limit the basic function of penile vascular tree in the elderly.

Intermittent injections of osteocalcin reverse autophagic dysfunction and endoplasmic reticulum stress resulting from diet-induced obesity in the vascular tissue via the NFκB-p65-dependent mechanism.

PubMed

Zhou, Bo; Li, Huixia; Liu, Jiali; Xu, Lin; Zang, Weijin; Wu, Shufang; Sun, Hongzhi

2013-06-15

The osteoblast-specific secreted molecule osteocalcin behaves as a hormone-regulating glucose and lipid metabolism, but the role of osteocalcin in cardiovascular disease (CVD) is not fully understood. In the present study, we investigated the effect of osteocalcin on autophagy and endoplasmic reticulum (ER) stress secondary to diet-induced obesity in the vascular tissue of mice and in vascular cell models and clarified the intracellular events responsible for osteocalcin-mediated effects. The evidences showed that intermittent injections of osteocalcin in mice fed the high-fat diet were associated with a reduced body weight gain, decreased blood glucose and improved insulin sensitivity compared with mice fed the high-fat diet receiving vehicle. Simultaneously, the administration of osteocalcin not only attenuated autophagy and ER stress but also rescued impaired insulin signaling in vascular tissues of mice fed a high-fat diet. Consistent with these results in vivo, the addition of osteocalcin reversed autophagy and ER stress and restored defective insulin sensitivity in vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in the presence of tunicamycin or in knockout XBP-1 (a transcription factor which mediates ER stress response) cells or in Atg7(-/-) cells. The protective effects of osteocalcin were nullified by suppression of Akt, mammalian target of rapamycin (mTOR) or nuclear factor kappa B (NFκB), suggesting that osteocalcin inhibits autophagy, ER stress and improves insulin signaling in the vascular tissue and cells under insulin resistance in a NFκB-dependent manner, which may be a promising therapeutic strategies of cardiovascular dysfunction secondary to obesity.

Effects of hypothyroidism on vascular /sup 125/I-albumin permeation and blood flow in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilton, R.G.; Pugliese, G.; Chang, K.

1989-05-01

Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern wasmore » observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.« less

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.

PubMed

Fraser, John K; Hicok, Kevin C; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution ® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

Numerical Simulation of the Flow in Vascular Grafts for Surgical Applications

NASA Astrophysics Data System (ADS)

McGah, Patrick; Aliseda, Alberto

2009-11-01

Numerical simulation of the human blood vessels, is becoming an important tool in surgical planning and research. Accurate vascular simulations might grant physicians the predictive capability to perform pre-surgical planning. We focus our attention on the implantation of vascular grafts. The high rate of failure of this common vascular interaction is intimately related to the fluid mechanics in the affected region and the subsequent wall tissue remodeling. Here, we will present our current work in developing a methodology for the numerical simulation of vascular grafts which incorporates physiologically realistic geometries and flow boundary conditions. In particular, we seek to correlate the wall shear stress and its spatial (WSSG) and temporal (OSI) variability to wall remodeling as observed in patient specific longitudinal studies. The pulsatility (Remean= 800 , Repeak= 2000, Wo = 2) of the flow gives rise to additional fluid dynamics phenomena such as instability, flow separation, transition, and unsteadiness. Our goal is to describe and evaluate their effect on the wall physiology.

The skeletal vascular system - Breathing life into bone tissue.

PubMed

Stegen, Steve; Carmeliet, Geert

2017-08-26

During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Live intramacrophagic Staphylococcus aureus as a potential cause of antibiotic therapy failure: observations in an in vivo mouse model of prosthetic vascular material infections.

PubMed

Boudjemaa, Rym; Steenkeste, Karine; Jacqueline, Cédric; Briandet, Romain; Caillon, Jocelyne; Boutoille, David; Le Mabecque, Virginie; Tattevin, Pierre; Fontaine-Aupart, Marie-Pierre; Revest, Matthieu

2018-06-12

To evaluate the significant role played by biofilms during prosthetic vascular material infections (PVMIs). We developed an in vivo mouse model of Staphylococcus aureus PVMI allowing its direct observation by confocal microscopy to describe: (i) the structure of biofilms developed on Dacron® vascular material; (ii) the localization and effect of antibiotics on these biostructures; and (iii) the interaction between bacteria and host tissues and cells during PVMI. In this model we demonstrated that the biofilm structures are correlated to the activity of antibiotics. Furthermore, live S. aureus bacteria were visualized inside the macrophages present at the biofilm sites, which is significant as antibiotics do not penetrate these immune cells. This intracellular situation may explain the limited effect of antibiotics and also why PVMIs can relapse after antibiotic therapy.

Building vascular networks.

PubMed

Bae, Hojae; Puranik, Amey S; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A; Khademhosseini, Ali

2012-11-14

Only a few engineered tissues-skin, cartilage, bladder-have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors

PubMed Central

Butler, Jason M.; Kobayashi, Hideki; Rafii, Shahin

2010-01-01

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an ‘angiocrine’ mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents. PMID:20094048

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors.

PubMed

Butler, Jason M; Kobayashi, Hideki; Rafii, Shahin

2010-02-01

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

The distribution and ultrastructure of the forming blood capillaries and the effect of apoptosis on vascularization in mouse embryonic molar mesenchyme.

PubMed

Yuan, Guohua; Zhang, Li; Yang, Guobin; Yang, Jingwen; Wan, Chunyan; Zhang, Lu; Song, Guangtai; Chen, Shuo; Chen, Zhi

2014-04-01

Vascularization is essential for organ and tissue development. Teeth develop through interactions between epithelium and mesenchyme. The developing capillaries in the enamel organ, the dental epithelial structure, occur simultaneously by mechanisms of vasculogenesis and angiogenesis at the onset of dentinogenesis. The vascular neoformation in the dental mesenchyme has been reported to start from the cap stage. However, the mechanisms of vascularization in the dental mesenchyme remain unknown. In the hope of understanding the mechanisms of the formation of dental mesenchymal vasculature, mouse lower molar germs from embryonic day (E) 13.5 to E16.5 were processed for immunostaining of CD31 and CD34, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and transmission electron microscopy (TEM). In addition, the role of apoptosis for the vascularization in dental mesenchyme was examined by in vitro culture of E14.0 lower molars in the presence of the apoptosis inhibitor (z-VAD-fmk) and a subsequent subrenal culture. Our results showed that CD31- and CD34-positive cells progressively entered the central part of the dental papilla from the peridental mesenchyme. For TEM, angioblasts, young capillaries with thick endothelium and endothelial cells containing vacuoles were observed in peripheral dental mesenchyme, suggesting vasculogenesis was taking place. The presence of lateral sprouting, cytoplasmic filopodia and transluminal bridges in the dental papilla suggested angiogenesis was also occurring. Inhibition of apoptosis delayed the angiogenic vascularization of the dental papilla. Therefore, these data demonstrated that molar mesenchyme is progressively vascularized by mechanisms of both vasculogenesis and angiogenesis and apoptosis partially contributes to the vascularization of the dental papilla.

Negating Tissue Contracture Improves Volume Maintenance and Longevity of In Vivo Engineered Tissues.

PubMed

Lytle, Ian F; Kozlow, Jeffrey H; Zhang, Wen X; Buffington, Deborah A; Humes, H David; Brown, David L

2015-10-01

Engineering large, complex tissues in vivo requires robust vascularization to optimize survival, growth, and function. Previously, the authors used a "chamber" model that promotes intense angiogenesis in vivo as a platform for functional three-dimensional muscle and renal engineering. A silicone membrane used to define the structure and to contain the constructs is successful in the short term. However, over time, generated tissues contract and decrease in size in a manner similar to capsular contracture seen around many commonly used surgical implants. The authors hypothesized that modification of the chamber structure or internal surface would promote tissue adherence and maintain construct volume. Three chamber configurations were tested against volume maintenance. Previously studied, smooth silicone surfaces were compared to chambers modified for improved tissue adherence, with multiple transmembrane perforations or lined with a commercially available textured surface. Tissues were allowed to mature long term in a rat model, before analysis. On explantation, average tissue masses were 49, 102, and 122 mg; average volumes were 74, 158 and 176 μl; and average cross-sectional areas were 1.6, 6.7, and 8.7 mm for the smooth, perforated, and textured groups, respectively. Both perforated and textured designs demonstrated significantly greater measures than the smooth-surfaced constructs in all respects. By modifying the design of chambers supporting vascularized, three-dimensional, in vivo tissue engineering constructs, generated tissue mass, volume, and area can be maintained over a long time course. Successful progress in the scale-up of construct size should follow, leading to improved potential for development of increasingly complex engineered tissues.

Computerized whole slide quantification shows increased microvascular density in pT2 prostate cancer as compared to normal prostate tissue.

PubMed

van Niekerk, Cornelis G; van der Laak, Jeroen A W M; Börger, M Elisa; Huisman, Henk-Jan; Witjes, J Alfred; Barentsz, Jelle O; Hulsbergen-van de Kaa, Christina A

2009-01-01

Contrast enhanced imaging enables powerful, non-invasive diagnostics, important for detection and staging of early prostate cancer. The uptake of contrast agent is increased in prostate cancer as compared to normal prostate tissue. To reveal the underlying physiological mechanisms, quantification of tissue components in pathology specimens may yield important information. Aim of this study was to investigate whether microvascularity is increased in prostate confined cancer (pT2). Radical prostatectomy specimens of 26 patients were selected for organ confined peripheral zone tumors which were restricted to one side of the prostate. Microvessels were visualized by immunohistochemistry against CD31. Specimens were scanned using a computer controlled microscope and scanning stage and vessels were recognized automatically. Pseudocolor mappings were produced showing number of vascular profiles (MVD), vascular area (MVA) and perimeter (MVP) in an overview of the entire prostate transection. MVD is a common measure for vascularity, whereas MVA represents the 3D vascular volume and MVP the perfused surface area. Mean, coefficient of variation and 75th percentile of these parameters were calculated automatically in manually indicated areas, consisting of the entire tumor area and the corresponding normal area in the contra lateral side of the prostate. The mappings clearly indicate areas of increased vascularity in prostate transections. In tumor tissue an increase was found compared to normal tissue of 81%, 49%, and 62% for mean MVD, mean MVA and mean MVP, respectively (P < 0.001 for all comparisons). In contrast, the heterogeneity in tumor vasculature was significantly decreased as compared to normal prostate (P < 0.001). Characteristics of microvasculature deviated significantly in pT2 prostate tumor as compared to normal tissue. Copyright 2008 Wiley-Liss, Inc.

Pattern and density of vascularization in mammalian testes, ovaries, and ovotestes.

PubMed

Lupiáñez, Darío G; Real, Francisca M; Dadhich, Rajesh K; Carmona, Francisco D; Burgos, Miguel; Barrionuevo, Francisco J; Jiménez, Rafael

2012-05-01

According to the classical paradigm, the vasculature of the embryonic testis is more dense and complex than that of the ovary, but recent studies based on whole-mount detection of Caveolin-1 (CAV1) as an endothelial cell marker, have suggested that the level of ovarian vascularization is higher than previously assumed. However, this new hypothesis has been neither tested using alternative methodology nor investigated in other mammalian species. In this paper, we have studied the vascularization process in the gonads of males and females of two mammalian species, the mouse (Mus musculus) and the Iberian mole (Talpa occidentalis). Our results show that the pattern of testis vascularization is very well conserved among mammals, including both pre- and postnatal stages of development and, at least in the mole, it is conserved irrespectively of whether the testicular tissue is XY or XX. We have shown that CAV1 is present not only in endothelial cells but also in prefollicular oocytes and in an ovarian population of somatic cortical cells. These data clearly establish that: (1) according to the classical hypothesis, the degree of vascularization of the developing ovary is lower than that of the testis, (2) ovarian vascularization is also evolutionarily conserved as it occurs similarly both in moles and in mice, and (3) that the degree of vascular development of the mammalian ovary is age-dependent increasing significatively at puberty. The expression of CAV1 in the ovary of most animal taxa, from nematodes to mammals, strongly suggests a role for this gene in the female meiosis. © 2012 WILEY PERIODICALS, INC.

Different Effects of Implanting Sensory Nerve or Blood Vessel on the Vascularization, Neurotization, and Osteogenesis of Tissue-Engineered Bone In Vivo

PubMed Central

Fan, Jun-jun; Mu, Tian-wang; Qin, Jun-jun; Bi, Long; Pei, Guo-xian

2014-01-01

To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve. PMID:25101279

Histopathological features of Proteus syndrome.

PubMed

Hoey, S E H; Eastwood, D; Monsell, F; Kangesu, L; Harper, J I; Sebire, N J

2008-05-01

Proteus syndrome is a rare, sporadic overgrowth disorder for which the underlying genetic defect remains unknown. Although the clinical course is well-described there is no systematic histopathological description of the lesional pathology. To describe the histopathological features encountered in a series of patients with Proteus syndrome from a single centre. Patients with Proteus syndrome who had undergone therapeutic surgical resection or biopsy were identified from a database and the histopathological findings were reviewed, with particular regard to descriptive features of the underlying tissue abnormality. There were 18 surgical specimens from nine patients, median age 4 years (range 1-9), classified into four main categories: soft-tissue swellings (lipomatous lesions), vascular anomalies (vascular malformation and haemangioma), macrodactyly (hamartomatous overgrowth) and others (sebaceous naevus and nonspecific features). In all cases, the clinical features of overgrowth were due to increased amounts of disorganized tissue, indicating a hamartomatous-type defect in which normal tissue constituents were present, but with an abnormal distribution and architecture. Vascular malformations represented a prominent category of lesions, accounting for 50% of the specimens, predominantly comprising lymphatic and lymphovascular malformations. No malignancy or cytological atypia was identified in any case. The histopathological features of lesions resected from children with Proteus syndrome predominantly include hamartomatous mixed connective tissue lesions, benign neoplasms such as lipomata, and lymphatic-rich vascular malformations.

The effects of Δ9-Tetrahydrocannabinole treatment on gonadal micro-vascularization and affected fertility examined by SEM and 3D-morphometry

NASA Astrophysics Data System (ADS)

Erlbacher, K. M. T.; Minnich, B.

2015-10-01

The present study focuses on the effects of Δ9-tetrahydrocannabinol (THC) on the reproductive system in nude rats with special emphasis on how Δ9-THC impacts the vascularization of testes which in turn indirectly influences fertility. Basically, Δ9-tetrahydrocannabinol (THC) causes not only negative (psychoactive) effects in the human body as cannabinole administration in medical use (dose-dependent) offers multiple new treatment opportunities such as pain relief or containment of various cancers. Concerning the reproductive system it strongly influences CB-receptors along the hypothalamic-pituitary-gonadal axis resulting in reduced plasma testosterone levels. There is also altered sperm quality parameters reported such as sperm motility or sperm count. On the other hand Δ9-THC effects endothelial growth factors (VEGF, Ang-1 etc.) respectively acts on their specific receptors which in turn modify angiogenesis and vascularization of tissues and organs (e.g. tumorous tissues). This leads to new therapeutical strategies in the suppression of various cancers by inhibiting (neo-)vascularization and in turn famishment of tumorous tissues (lack of nutrition supply). Here we studied the micro-vascularization of gonads in a long-term THC-treated nude rat model by vascular corrosion casting, SEM and 3D-morphometry.

Human adipose-derived stem cells promote vascularization of collagen-based scaffolds transplanted into nude mice

PubMed Central

Cherubino, Mario; Valdatta, Luigi; Balzaretti, Riccardo; Pellegatta, Igor; Rossi, Federica; Protasoni, Marina; Tedeschi, Alessandra; Accolla, Roberto S; Bernardini, Giovanni; Gornati, Rosalba

2016-01-01

Aim: After in vivo implantation of cell-loaded devices, only the cells close to the capillaries can obtain nutrients to maintain their functions. It is known that factors secreted by stem cells, rather than stem cells themselves, are fundamental to guarantee new vascularization in the area of implant. Materials & methods: To investigate this possibility, we have grafted mice with Bilayer and Flowable Integra® scaffolds, loaded or not with human adipose-derived stem cells. Results: Our results support the therapeutic potential of human adipose-derived stem cells to induce new vascular networks of engineered organs and tissues. Conclusion: This finding suggests that our approach can help to form new vascular networks that allow sufficient vascularization of engineered organs and tissues in cases of difficult wound healing due to ischemic conditions. PMID:26965659

Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome

PubMed Central

Wu, Wei; Zhang, Junlan; Yang, Wenli; Hu, Bingqian

2016-01-01

Abstract Background and Aim Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS. Methods Splenectomy was performed in CBDL animals. Monocyte levels in different tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were evaluated with vascular endothelial growth factor‐A (VEGF‐A) levels, angiogenesis, and alveolar–arterial oxygen gradient (AaPO2). Liver abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation (CK‐19), and enzymatic changes. Results Monocyte levels increased in the lung and liver after CBDL and were accompanied by elevated circulating monocyte numbers. Splenectomy significantly decreased monocyte accumulation, VEGF‐A levels, and angiogenesis in CBDL animal lung and improved AaPO2 levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal. Conclusions Splenic reservoir monocytes are a major source for lung monocyte accumulation after CBDL, and spleen removal attenuates the development of experimental HPS. Liver monocytes may have different origins, and accumulation is exacerbated after depletion of splenic reservoir monocytes. Tissue specific monocyte alterations, influenced by the spleen reservoir, have a significant impact on pulmonary complications of liver disease. PMID:27029414

Bone tissue phantoms for optical flowmeters at large interoptode spacing generated by 3D-stereolithography

PubMed Central

Binzoni, Tiziano; Torricelli, Alessandro; Giust, Remo; Sanguinetti, Bruno; Bernhard, Paul; Spinelli, Lorenzo

2014-01-01

A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laser-Doppler flowmeter, is also presented. PMID:25136496

Sox17 drives functional engraftment of endothelium converted from non-vascular cells.

PubMed

Schachterle, William; Badwe, Chaitanya R; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M; Rafii, Shahin

2017-01-16

Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.

Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

PubMed

Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

2013-12-01

Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, <100 μm in diameter). These were examined for functionality and compared with adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as arterial wall calcification and possible applications to regenerative therapies involving each vessel wall-resident stromal population.

* Central Growth Factor Loaded Depots in Bone Tissue Engineering Scaffolds for Enhanced Cell Attraction.

PubMed

Quade, Mandy; Knaack, Sven; Akkineni, Ashwini Rahul; Gabrielyan, Anastasia; Lode, Anja; Rösen-Wolff, Angela; Gelinsky, Michael

2017-08-01

Tissue engineering, the application of stem and progenitor cells in combination with an engineered extracellular matrix, is a promising strategy for bone regeneration. However, its success is limited by the lack of vascularization after implantation. The concept of in situ tissue engineering envisages the recruitment of cells necessary for tissue regeneration from the host environment foregoing ex vivo cell seeding of the scaffold. In this study, we developed a novel scaffold system for enhanced cell attraction, which is based on biomimetic mineralized collagen scaffolds equipped with a central biopolymer depot loaded with chemotactic agents. In humid milieu, as after implantation, the signaling factors are expected to slowly diffuse out of the central depot forming a gradient that stimulates directed cell migration toward the scaffold center. Heparin, hyaluronic acid, and alginate have been shown to be capable of depot formation. By using vascular endothelial growth factor (VEGF) as model factor, it was demonstrated that the release kinetics can be adjusted by varying the depot composition. While alginate and hyaluronic acid are able to reduce the initial burst and prolong the release of VEGF, the addition of heparin led to a much stronger retention that resulted in an almost linear release over 28 days. The biological activity of released VEGF was proven for all variants using an endothelial cell proliferation assay. Furthermore, migration experiments with endothelial cells revealed a relationship between the degree of VEGF retention and migration distance: cells invaded deepest in scaffolds containing a heparin-based depot indicating that the formation of a steep gradient is crucial for cell attraction. In conclusion, this novel in situ tissue engineering approach, specifically designed to recruit and accommodate endogenous cells upon implantation, appeared highly promising to stimulate cell invasion, which in turn would promote vascularization and finally new bone formation.

Perivascular Adipose Tissue as a Relevant Fat Depot for Cardiovascular Risk in Obesity.

PubMed

Costa, Rafael M; Neves, Karla B; Tostes, Rita C; Lobato, Núbia S

2018-01-01

Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out.

Effects Of Continuous Argon Laser Irradiation On Canine And Autopsied Human Cardiac Tissue

NASA Astrophysics Data System (ADS)

Ben-Shachar, Giora; Sivakoff, Mark; Bernard, Steven L.; Dahms, Beverly B.; Riemenschneider, Thomas A.

1984-10-01

In eight human formalin preserved cardiac specimens, various cardiac and vascular obstructions were relieved by argon laser irradiation. Interatrial communication was also produced by a transar'rial approach in a live dog. In-vivo fresh canine cardiac tissues required power density of at feast 80, 90, and 110 watts/cm2 for vaporization of myocardial, vascular and valvular tissues respectively. The fiber tip to tissue distance (effective irradiation distance) for effective vaporization was less than I mm for vascular and valvular tissues and less than 4 mm for myocardium. Light microscopy showed four zones of histological damage common to all tissues - central crater surrounded by layers of charring, vacuolization and coagulation necorsis. Myocardium showed additionally a layer of normal appearing muscle cells (skip area) surrounded by a peripheral coagulation halo. Laser irradiation effects on valvular tissue showed the most lateral extension of coagulation necrosis. It is concluded that palliation and treatment of certain congenital heart defects by laser irradiation is anatomi-cally feasible and may be safe for in vivo application when low power output and short exposure time are used from a very short irradiation distance.

Uncultivated stromal vascular fraction is equivalent to adipose-derived stem and stromal cells on porous polyurethrane scaffolds forming adipose tissue in vivo.

PubMed

Griessl, Michael; Buchberger, Anna-Maria; Regn, Sybille; Kreutzer, Kilian; Storck, Katharina

2018-06-01

To find an alternative approach to contemporary techniques in tissue augmentation and reconstruction, tissue engineering strategies aim to involve adipose-derived stem and stromal cells (ASCs) harboring a strong differentiation potential into various tissue types such as bone, cartilage, and fat. Animal research. The stromal vascular fraction (SVF) was used directly as a cell source to provide a potential alternative to contemporary ASC-based adipose tissue engineering. Seeded in TissuCol fibrin, we applied ASCs or SVF cells to porous, degradable polyurethane (PU) scaffolds. We successfully demonstrated the in vivo generation of volume-stable, well-vascularized PU-based constructs containing host-derived mature fat pads. Seeded human stem cells served as modulators of host-cell migration rather than differentiating themselves. We further demonstrated that preliminary culture of SVF cells was not necessary. Our results bring adipose tissue engineering, together with automated processing devices, closer to clinical applicability. The time-consuming and cost-intensive culture and induction of the ASCs is not necessary. NA. Laryngoscope, 128:E206-E213, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Interaction of intraluminal tissue and coronary sinus lead stabilized with stent placement.

PubMed

Balázs, Tibor; Merkely, Béla; Bognár, Eszter; Zima, Endre

2013-04-01

The aim of our investigation was to examine the intraluminal interaction of the vascular tissue and the implanted coronary sinus lead stabilized with stent on two human hearts removed before transplantation. The coronary sinus lumen was sectioned under operational microscope and opened carefully. The leads and stents were found separately positioned beside each other completely covered by an intact intimal tissue layer. No sign of occluding proliferative tissue was observed. Stent fixation technique and extraction of the CS lead in our cases did not have any particular damaging effect on the vascular system. © 2012 Wiley Periodicals, Inc.

Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

PubMed

Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

2018-02-01

 Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Synchrotron study of metal localization in Typha latifolia L. root sections

DOE PAGES

Qian, Yu; Jones, Keith W.; Feng, Huan; ...

2015-09-15

Understanding mechanisms that control plant root metal assimilation in soil is critical to the sustainable management of metal-contaminated land. With the assistance of the synchrotron X-ray fluorescence technique, this study investigated possible mechanisms that control the localization of Fe, Cu, Mn, Pb and Zn in the root tissues of Typha latifolia L. collected from a contaminated wetland. Metal localizations especially in the case of Fe and Pb in the dermal tissue and the vascular bundles were different. Cluster analysis was performed to divide the dermal tissue into iron-plaque-enriched dermal tissue and regular dermal tissue based on the spatial distribution ofmore » Pb and Fe. Factor analysis showed that Cu and Zn were closely correlated to each other in the dermal tissues. The association of Cu, Zn and Mn with Fe was strong in both regular dermal tissue and iron-plaque-enriched dermal tissue, while significant (p < 0.05) correlation of Fe with Pb was only observed in tissues enriched with iron plaque. In the vascular bundles, Zn, Mn and Cu showed strong association, suggesting that the localization of these three elements was controlled by a similar mechanism. Iron plaque in the peripheral dermal tissues acted as a barrier for Pb and a buffer for Zn, Cu and Mn. Furthermore, the Casparian strip regulated the transportation of metals from dermal tissues to the vascular bundles. The results suggested that the mechanisms controlling metal localization in root tissues varied with both tissue types and metals.« less

Bio-chemo-mechanical models of vascular mechanics

PubMed Central

Kim, Jungsil; Wagenseil, Jessica E.

2014-01-01

Models of vascular mechanics are necessary to predict the response of an artery under a variety of loads, for complex geometries, and in pathological adaptation. Classic constitutive models for arteries are phenomenological and the fitted parameters are not associated with physical components of the wall. Recently, microstructurally-linked models have been developed that associate structural information about the wall components with tissue-level mechanics. Microstructurally-linked models are useful for correlating changes in specific components with pathological outcomes, so that targeted treatments may be developed to prevent or reverse the physical changes. However, most treatments, and many causes, of vascular disease have chemical components. Chemical signaling within cells, between cells, and between cells and matrix constituents affects the biology and mechanics of the arterial wall in the short- and long-term. Hence, bio-chemo-mechanical models that include chemical signaling are critical for robust models of vascular mechanics. This review summarizes bio-mechanical and bio-chemo-mechanical models with a focus on large elastic arteries. We provide applications of these models and challenges for future work. PMID:25465618

Alexis Carrel (1873-1944): visionary vascular surgeon and pioneer in organ transplantation.

PubMed

Aida, Lai

2014-08-01

Alexis Carrel was a French surgeon in the 20th century. He made significant contributions to many advances in the fields of vascular surgery, cardiothoracic surgery and organ transplantation. He demonstrated that blood vessels can be united end-to-end and pioneered the triangulation suturing technique in vascular anastomosis. The methods he developed are still in use to this day. He insisted on the importance of absolute asepsis in vascular surgery when such practices were almost unheard of. He was also considered the father of solid organ transplantation. He was awarded the Nobel Prize in recognition of his work. Together with Charles Lindbergh, he developed the extracorporeal perfusion pump to keep organs alive outside the human body. His contribution to medicine also extended to tissue culture and wound management. He was one of the most controversial figures of his generation, believing in the idea of genetic superiority and eugenics and he was associated with fascism in the 1930s. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Expression and distribution of endocan in human tissues.

PubMed

Zhang, S M; Zuo, L; Zhou, Q; Gui, S Y; Shi, R; Wu, Q; Wei, W; Wang, Y

2012-04-01

Endocan is a novel human endothelial cell specific molecule. Its expression is regulated by cytokines and vascular endothelial growth factor (VEGF). The distribution of endocan in normal human tissues, however, remains unclear. We examined the expression of endocan in normal human tissue using immunohistochemical stains. Endocan was expressed in actively proliferative or neogeneic tissues and cells such as glandular tissues, endothelium of neovasculature, bronchial epithelium, germinal centers of lymph nodes etc. Endocan was not present in silent or resting tissues or cells such as endothelium of great arteries and spleen etc. Our findings suggest that endocan may act as a marker for angiogenesis or oncogenesis and could be regarded as a candidate gene for inflammatory tissue, neoplasia, tumor development and metastasis. The expression level of endocan may assist early diagnosis and prognosis of some tumors.

Destructive effect of HIFU on rabbit embedded endometrial carcinoma tissues and their vascularities

PubMed Central

Guan, Liming; Xu, Gang

2017-01-01

Objectives To evaluate damage effect of High-intensity focused ultrasound on early stage endometrial cancer tissues and their vascularities. Materials and Methods Rabbit endometrial cancer models were established via tumor blocks implantation for a prospective control study. Ultrasonic ablation efficacy was evaluated by pathologic and imaging changes. The target lesions of experimental rabbits before and after ultrasonic ablation were observed after autopsy. The slides were used for hematoxylin-eosin staining, elastic fiber staining and endothelial cell staining; the slides were observed by optical microscopy. One slide was observed by electron microscopy. Then the target lesions of experimental animals with ultrasonic ablation were observed by vascular imaging, one group was visualized by digital subtract angiography, one group was quantified by color Doppler flow imaging, and one group was detected by dye perfusion. SPSS 19.0 software was used for statistical analyses. Results Histological examination indicated that High-intensity focused ultrasound caused the tumor tissues and their vascularities coagulative necrosis. Tumor vascular structure components including elastic fiber, endothelial cells all were destroyed by ultrasonic ablation. Digital subtract angiography showed tumor vascular shadow were dismissed after ultrasonic ablation. After ultrasonic ablation, gray-scale of tumor nodules enhanced in ultrasonography, tumor peripheral and internal blood flow signals disappeared or significantly reduced in color Doppler flow imaging. Vascular perfusion performed after ultrasonic ablation, tumor vessels could not filled by dye liquid. Conclusion High-intensity focused ultrasound as a noninvasive method can destroy whole endometrial cancer cells and their supplying vascularities, which maybe an alternative approach of targeted therapy and new antiangiogenic strategy for endometrial cancer. PMID:28121624

Destructive effect of HIFU on rabbit embedded endometrial carcinoma tissues and their vascularities.

PubMed

Guan, Liming; Xu, Gang

2017-03-21

To evaluate damage effect of High-intensity focused ultrasound on early stage endometrial cancer tissues and their vascularities. Rabbit endometrial cancer models were established via tumor blocks implantation for a prospective control study. Ultrasonic ablation efficacy was evaluated by pathologic and imaging changes. The target lesions of experimental rabbits before and after ultrasonic ablation were observed after autopsy. The slides were used for hematoxylin-eosin staining, elastic fiber staining and endothelial cell staining; the slides were observed by optical microscopy. One slide was observed by electron microscopy. Then the target lesions of experimental animals with ultrasonic ablation were observed by vascular imaging, one group was visualized by digital subtract angiography, one group was quantified by color Doppler flow imaging, and one group was detected by dye perfusion.SPSS 19.0 software was used for statistical analyses. Histological examination indicated that High-intensity focused ultrasound caused the tumor tissues and their vascularities coagulative necrosis. Tumor vascular structure components including elastic fiber, endothelial cells all were destroyed by ultrasonic ablation. Digital subtract angiography showed tumor vascular shadow were dismissed after ultrasonic ablation. After ultrasonic ablation, gray-scale of tumor nodules enhanced in ultrasonography, tumor peripheral and internal blood flow signals disappeared or significantly reduced in color Doppler flow imaging. Vascular perfusion performed after ultrasonic ablation, tumor vessels could not filled by dye liquid. High-intensity focused ultrasound as a noninvasive method can destroy whole endometrial cancer cells and their supplying vascularities, which maybe an alternative approach of targeted therapy and new antiangiogenic strategy for endometrial cancer.

Venous-derived angioblasts generate organ-specific vessels during zebrafish embryonic development.

PubMed

Hen, Gideon; Nicenboim, Julian; Mayseless, Oded; Asaf, Lihee; Shin, Masahiro; Busolin, Giorgia; Hofi, Roy; Almog, Gabriella; Tiso, Natascia; Lawson, Nathan D; Yaniv, Karina

2015-12-15

Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. Although it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions, the embryonic origins of tissue-specific vessels and the molecular mechanisms regulating their formation are poorly understood. The subintestinal plexus of the zebrafish embryo comprises vessels that vascularize the gut, liver and pancreas and, as such, represents an ideal model in which to investigate the early steps of organ-specific vessel formation. Here, we show that both arterial and venous components of the subintestinal plexus originate from a pool of specialized angioblasts residing in the floor of the posterior cardinal vein (PCV). Using live imaging of zebrafish embryos, in combination with photoconvertable transgenic reporters, we demonstrate that these angioblasts undergo two phases of migration and differentiation. Initially, a subintestinal vein forms and expands ventrally through a Bone Morphogenetic Protein-dependent step of collective migration. Concomitantly, a Vascular Endothelial Growth Factor-dependent shift in the directionality of migration, coupled to the upregulation of arterial markers, is observed, which culminates with the generation of the supraintestinal artery. Together, our results establish the zebrafish subintestinal plexus as an advantageous model for the study of organ-specific vessel development and provide new insights into the molecular mechanisms controlling its formation. More broadly, our findings suggest that PCV-specialized angioblasts contribute not only to the formation of the early trunk vasculature, but also to the establishment of late-forming, tissue-specific vascular beds. © 2015. Published by The Company of Biologists Ltd.

Emergency repair of upper extremity large soft tissue and vascular injuries with flow-through anterolateral thigh free flaps.

PubMed

Zhan, Yi; Fu, Guo; Zhou, Xiang; He, Bo; Yan, Li-Wei; Zhu, Qing-Tang; Gu, Li-Qiang; Liu, Xiao-Lin; Qi, Jian

2017-12-01

Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries. Copyright © 2017. Published by Elsevier Ltd.

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques

PubMed Central

Curtze, Sven C.; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-01-01

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron – and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration. PMID:26980376

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques.

PubMed

Curtze, Sven C; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-03-16

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron - and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration.

Epithelioid Hemangioendothelioma: A Rare Vascular Tumor

PubMed Central

Lakshmi, S Vidya; Prabhavathy, D; Jayakumar, S; Janaki, C; Tharini, G K

2012-01-01

Epithelioid hemangioendothelioma is an intermediate-grade vascular tumor arising from the vascular endothelium, which usually arises in soft tissue, and skin involvement is extremely rare. We report a case that presented with primary cutaneous tumor involving the whole limb and was present since birth. PMID:22470212

The gene encoding the catalytically inactive beta-amylase BAM4 involved in starch breakdown in Arabidopsis leaves is expressed preferentially in vascular tissues in source and sink organs.

PubMed

Francisco, Perigio; Li, Jing; Smith, Steven M

2010-07-15

Genetic studies in Arabidopsis thaliana have shown that two members of the beta-amylase (BAM) family BAM3 and BAM4 are required for leaf starch breakdown at night. Both are plastid proteins and while BAM3 encodes an active BAM, BAM4 is not an active alpha-1,4-glucan hydrolase. To gain further insight into the possible function of BAM4 we constructed reporter genes using promoters for both BAM3 and BAM4 genes, driving beta-glucuronidase (GUS) and luciferase (LUC) expression in transgenic Arabidopsis plants. Both promoters directed expression in vascular tissue throughout the plant including cotyledons, leaves, petioles, stems, petals, siliques and roots. Tissue sections showed expression to be focused in phloem cells in stem and petiole. The BAM3 promoter was also expressed strongly throughout the photosynthetic tissues of leaves, sepals and siliques, whereas the BAM4 promoter was not. Conversely, the BAM4 promoter was active in root tip but the BAM3 promoter was not. To confirm these expression patterns and to compare with expression of other starch genes we carried-out RT-PCR analysis on RNA from vascular (replum) and non-vascular (valve) tissues of siliques. This confirmed that BAM4 expression together with RAM1 (BAM5) and GWD2 genes is stronger in the replum than the valve, whereas BAM3 is strong in both tissues. These results show that even though BAM3 and BAM4 genes apparently interact genetically in leaf starch metabolism, BAM4 is preferentially expressed in non-photosynthetic vascular tissue, so revealing a potentially greater level of complexity in the control of starch breakdown than had previously been recognised. Copyright (c) 2010 Elsevier GmbH. All rights reserved.

Tissue Engineering Strategies for Promoting Vascularized Bone Regeneration

PubMed Central

Almubarak, Sarah; Nethercott, Hubert; Freeberg, Marie; Beaudon, Caroline; Jha, Amit; Jackson, Wesley; Marcucio, Ralph; Miclau, Theodore; Healy, Kevin; Bahney, Chelsea

2016-01-01

This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how adipose derived stem cells compare to bone marrow derived mesenchymal stem cells in the promotion of angiogenesis. We conclude this review with a discussion of a novel approach to bone regeneration through a cartilage intermediate, and discuss why it has the potential to be more effective than traditional bone grafting methods. PMID:26608518

Structure and vascular tissue expression of duplicated TERMINAL EAR1-like paralogues in poplar.

PubMed

Charon, Céline; Vivancos, Julien; Mazubert, Christelle; Paquet, Nicolas; Pilate, Gilles; Dron, Michel

2010-02-01

TERMINAL EAR1-like (TEL) genes encode putative RNA-binding proteins only found in land plants. Previous studies suggested that they may regulate tissue and organ initiation in Poaceae. Two TEL genes were identified in both Populus trichocarpa and the hybrid aspen Populus tremula x P. alba, named, respectively, PoptrTEL1-2 and PtaTEL1-2. The analysis of the organisation around the PoptrTEL genes in the P. trichocarpa genome and the estimation of the synonymous substitution rate for PtaTEL1-2 genes indicate that the paralogous link between these two Populus TEL genes probably results from the Salicoid large-scale gene-duplication event. Phylogenetic analyses confirmed their orthology link with the other TEL genes. The expression pattern of both PtaTEL genes appeared to be restricted to the mother cells of the plant body: leaf founder cells, leaf primordia, axillary buds and root differentiating tissues, as well as to mother cells of vascular tissues. Most interestingly, PtaTEL1-2 transcripts were found in differentiating cells of secondary xylem and phloem, but probably not in the cambium itself. Taken together, these results indicate specific expression of the TEL genes in differentiating cells controlling tissue and organ development in Populus (and other Angiosperm species).

Assembly of tissue engineered blood vessels with spatially-controlled heterogeneities.

PubMed

Strobel, Hannah A; Hookway, Tracy; Piola, Marco; Fiore, Gianfranco Beniamino; Soncini, Monica; Alsberg, Eben; Rolle, Marsha

2018-05-04

Tissue-engineered human blood vessels may enable in vitro disease modeling and drug screening to accelerate advances in vascular medicine. Existing methods for tissue engineered blood vessel (TEBV) fabrication create homogenous tubes not conducive to modeling the focal pathologies characteristic of vascular disease. We developed a system for generating self-assembled human smooth muscle cell ring-units, which were fused together into TEBVs. The goal of this study was to assess the feasibility of modular assembly and fusion of ring building units to fabricate spatially-controlled, heterogeneous tissue tubes. We first aimed to enhance fusion and reduce total culture time, and determined that reducing ring pre-culture duration improved tube fusion. Next, we incorporated electrospun polymer ring units onto tube ends as reinforced extensions, which allowed us to cannulate tubes after only 7 days of fusion, and culture tubes with luminal flow in a custom bioreactor. To create focal heterogeneities, we incorporated gelatin microspheres into select ring units during self-assembly, and fused these rings between ring units without microspheres. Cells within rings maintained their spatial position within tissue tubes after fusion. This work describes a platform approach for creating modular TEBVs with spatially-defined structural heterogeneities, which may ultimately be applied to mimic focal diseases such as intimal hyperplasia or aneurysm.

Biomimetic hybrid porous scaffolds immobilized with platelet derived growth factor-BB promote cellularization and vascularization in tissue engineering.

PubMed

Murali, Ragothaman; Ponrasu, Thangavel; Cheirmadurai, Kalirajan; Thanikaivelan, Palanisamy

2016-02-01

Development of hybrid scaffolds with synergistic combination of growth factor is a promising approach to promote early in vivo wound repair and tissue regeneration. Here, we show the rapid wound healing in Wistar albino rats using biomimetic collagen-poly(dialdehyde) guar gum based hybrid porous scaffolds covalently immobilized with platelet derived growth factor-BB. The immobilized platelet derived growth factor in the hybrid scaffolds not only enhance the total protein, collagen, hexosamine, and uronic acid contents in the granulation tissue but also provide stronger tissues. The wound closure analysis reveal that the complete epithelialization period is 15.4 ± 0.9 days for collagen-poly(dialdehyde) guar gum-platelet derived growth factor hybrid scaffolds, whereas it is significantly higher for control, collagen, collagen- poly(dialdehyde) guar gum and povidine-iodine treated groups. Further, the histological evaluation shows that the immobilized platelet derived growth factor in the hybrid scaffolds induced a more robust cellular and vascular response in the implanted site. Hence, we demonstrate that the collagen-poly(dialdehyde) guar gum hybrid scaffolds loaded with platelet derived growth factor stimulates chemotactic effects in the implanted site to promote rapid tissue regeneration and wound repair without the assistance of antibacterial agents. © 2015 Wiley Periodicals, Inc.

Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0244 TITLE: Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival...observed effects these particles have on allograft survival. Key Words CTA Composite Tissue Allotransplantation VCA Vascularized Composite

Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma

PubMed Central

Strub, Graham M.; Kirsh, Andrew L.; Whipple, Mark E.; Kuo, Winston P.; Keller, Rachel B.; Kapur, Raj P.; Majesky, Mark W.; Perkins, Jonathan A.

2016-01-01

Infantile hemangioma (IH) is the most common vascular tumor of infancy, and it uniquely regresses in response to oral propranolol. MicroRNAs (miRNAs) have emerged as key regulators of vascular development and are dysregulated in many disease processes, but the role of miRNAs in IH growth has not been investigated. We report expression of C19MC, a primate-specific megacluster of miRNAs expressed in placenta with rare expression in postnatal tissues, in glucose transporter 1–expressing (GLUT-1–expressing) IH endothelial cells and in the plasma of children with IH. Tissue or circulating C19MC miRNAs were not detectable in patients having 9 other types of vascular anomalies or unaffected children, identifying C19MC miRNAs as the first circulating biomarkers of IH. Levels of circulating C19MC miRNAs correlated with IH tumor size and propranolol treatment response, and IH tissue from children treated with propranolol or from children with partially involuted tumors contained lower levels of C19MC miRNAs than untreated, proliferative tumors, implicating C19MC miRNAs as potential drivers of IH pathogenesis. Detection of C19MC miRNAs in the circulation of infants with IH may provide a specific and noninvasive means of IH diagnosis and identification of candidates for propranolol therapy as well as a means to monitor treatment response. PMID:27660822

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo.

PubMed

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-09-19

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25-100 μm wide) and minibeams (200-800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a(+) thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.

Cytocompatibility and biologic characteristics of synthetic scaffold materials of rabbit acellular vascular matrix combining with human-like collagen I.

PubMed

Liu, Xuqian; Wang, Jie; Dong, Fusheng; Song, Peng; Tian, Songbo; Li, Hexiang; Hou, Yali

2017-10-01

Scaffold material provides a three-dimensional growing environment for seed cells in the research field of tissue engineering. In the present study, rabbit arterial blood vessel cells were chemically removed with trypsin and Triton X-100 to prepare rabbit acellular vascular matrix scaffold material. Observation by He&Masson staining revealed that no cellular components or nuclei existed in the vascular intima and media after decellularization. Human-like collagen I was combined with acellular vascular matrix by freeze-drying to prepare an acellular vascular matrix-0.25% human-like collagen I scaffold to compensate for the extracellular matrix loss during the decellularization process. We next performed a series of experiments to test the water absorbing quality, biomechanics, pressure resistance, cytotoxicity, and ultra-micro structure of the acellular vascular matrix composite material and natural rabbit artery and found that the acellular vascular matrix-0.25% human-like collagen I material behaved similarly to natural rabbit artery. In conclusion, the acellular vascular matrix-0.25% human-like collagen I composite material provides a new approach and lays the foundation for novel scaffold material research into tissue engineering of blood vessels.

Skin allograft and vascularized composite allograft: potential for long-term efficacy in the context of lymphatic modulation.

PubMed

Rinkinen, Jacob; Selley, Ryan; Agarwal, Shailesh; Loder, Shawn; Levi, Benjamin

2014-01-01

Tissue transplantation restores form and function in burn patients. The treatment of burn injuries is influenced by severity, location, and the percentage of total body surface area. There have been a number of different techniques developed to temporize and repair the destroyed tissue. However, in patients with large wound burden, sufficient donor site tissue may not be available for autograft harvesting. Such extensive burns necessitate other temporary and permanent options for wound coverage such as skin or vascularized composite allografts (VCA). Rejection of these tissues presents an ongoing problem which is currently managed using a host of systemic immunosuppressive medications. This article discusses the mechanism behind the innate and adaptive immune systems rejection of the allografts. By understanding these pathways, various techniques using immunomodulatory protocols have led to increased allograft survival. However, our primary interest lies in the initial recognition of the graft. We tailor this article to have a specific emphasis on lymphatic modulation as a potential adjunctive therapy. Reviews of the studies evaluating the effect of lymph node modulation on graft survival are described with future implications to allograft transplant research.

Modeling steady state SO2-dependent changes in capillary ATP concentration using novel O2 micro-delivery methods

PubMed Central

Ghonaim, Nour W.; Fraser, Graham M.; Ellis, Christopher G.; Yang, Jun; Goldman, Daniel

2013-01-01

Adenosine triphosphate (ATP) is known to be released from the erythrocyte in an oxygen (O2) dependent manner. Since ATP is a potent vasodilator, it is proposed to be a key regulator in the pathway that mediates micro-vascular response to varying tissue O2 demand. We propose that ATP signaling mainly originates in the capillaries due to the relatively long erythrocyte transit times in the capillary and the short ATP diffusion distance to the electrically coupled endothelium. We have developed a computational model to investigate the effect of delivering or removing O2 to limited areas at the surface of a tissue with an idealized parallel capillary array on total ATP concentration. Simulations were conducted when exposing full surface to perturbations in tissue O2 tension (PO2) or locally using a circular micro-outlet (~100 μm in diameter), a square micro-slit (200 × 200 μm), or a rectangular micro-slit (1000 μm wide × 200 μm long). Results indicated the rectangular micro-slit has the optimal dimensions for altering hemoglobin saturations (SO2) in sufficient number capillaries to generate effective changes in total [ATP]. This suggests a threshold for the minimum number of capillaries that need to be stimulated in vivo by imposed tissue hypoxia to induce a conducted micro-vascular response. SO2 and corresponding [ATP] changes were also modeled in a terminal arteriole (9 μm in diameter) that replaces 4 surface capillaries in the idealized network geometry. Based on the results, the contribution of terminal arterioles to the net change in [ATP] in the micro-vascular network is minimal although they would participate as O2 sources thus influencing the O2 distribution. The modeling data presented here provide important insights into designing a novel micro-delivery device for studying micro-vascular O2 regulation in the capillaries in vivo. PMID:24069001

Vascular wall progenitor cells in health and disease.

PubMed

Psaltis, Peter J; Simari, Robert D

2015-04-10

The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease. © 2015 American Heart Association, Inc.

Immunocytolocalization of extensin in developing soybean seed coats by immunogold-silver staining and by tissue printing on nitrocellulose paper

PubMed Central

1987-01-01

In soybean seed coats the accumulation of the hydroxyproline-rich glycoprotein extensin is regulated in a developmental and tissue- specific manner. The time course of appearance of extensin during seed development was studied by Western blot analysis and by immunogold- silver localization. Using these techniques extensin was first detected at 16-18 d after anthesis, increasing during development to high levels at 24 d after anthesis. Immunogold-silver localization of extensin in the seed coat showed marked deposition of the glycoprotein in the walls of palisade epidermal cells and hourglass cells. The immunolocalization of extensin in developing soybean seeds was also made by a new technique--tissue printing on nitrocellulose paper. It was found that extensin is primarily localized in the seed coat, hilum, and vascular elements of the seed. PMID:3693394

Advances in Skin Regeneration Using Tissue Engineering.

PubMed

Vig, Komal; Chaudhari, Atul; Tripathi, Shweta; Dixit, Saurabh; Sahu, Rajnish; Pillai, Shreekumar; Dennis, Vida A; Singh, Shree R

2017-04-07

Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.

A highly printable and biocompatible hydrogel composite for direct printing of soft and perfusable vasculature-like structures.

PubMed

Suntornnond, Ratima; Tan, Edgar Yong Sheng; An, Jia; Chua, Chee Kai

2017-12-04

Vascularization is one major obstacle in bioprinting and tissue engineering. In order to create thick tissues or organs that can function like original body parts, the presence of a perfusable vascular system is essential. However, it is challenging to bioprint a hydrogel-based three-dimensional vasculature-like structure in a single step. In this paper, we report a new hydrogel-based composite that offers impressive printability, shape integrity, and biocompatibility for 3D bioprinting of a perfusable complex vasculature-like structure. The hydrogel composite can be used on a non-liquid platform and is printable at human body temperature. Moreover, the hydrogel composite supports both cell proliferation and cell differentiation. Our results represent a potentially new vascularization strategy for 3D bioprinting and tissue engineering.

Apical dominance in saffron and the involvement of the branching enzymes CCD7 and CCD8 in the control of bud sprouting

PubMed Central

2014-01-01

Background In saffron (Crocus sativus), new corms develop at the base of every shoot developed from the maternal corm, a globular underground storage stem. Since the degree of bud sprouts influences the number and size of new corms, and strigolactones (SLs) suppress growth of pre-formed axillary bud, it was considered appropriate to investigate SL involvement in physiology and molecular biology in saffron. We focused on two of the genes within the SL pathway, CCD7 and CCD8, encoding carotenoid cleavage enzymes required for the production of SLs. Results The CsCCD7 and CsCCD8 genes are the first ones isolated and characterized from a non-grass monocotyledonous plant. CsCCD7 and CsCCD8 expression showed some overlapping, although they were not identical. CsCCD8 was highly expressed in quiescent axillary buds and decapitation dramatically reduced its expression levels, suggesting its involvement in the suppression of axillary bud outgrowth. Furthermore, in vitro experiments showed also the involvement of auxin, cytokinin and jasmonic acid on the sprouting of axillary buds from corms in which the apical bud was removed. In addition, CsCCD8 expression, but not CsCCD7, was higher in the newly developed vascular tissue of axillary buds compared to the vascular tissue of the apical bud. Conclusions We showed that production and transport of auxin in saffron corms could act synergistically with SLs to arrest the outgrowth of the axillary buds, similar to the control of above-ground shoot branching. In addition, jasmonic acid seems to play a prominent role in bud dormancy in saffron. While cytokinins from roots promote bud outgrowth. In addition the expression results of CsCCD8 suggest that SLs could positively regulate procambial activity and the development of new vascular tissues connecting leaves with the mother corm. PMID:24947472

Effect of electromagnetic pulse exposure on brain micro vascular permeability in rats.

PubMed

Ding, Gui-Rong; Li, Kang-Chu; Wang, Xiao-Wu; Zhou, Yong-Chun; Qiu, Lian-Bo; Tan, Juan; Xu, Sheng-Long; Guo, Guo-Zhen

2009-06-01

To observe the effect of electromagnetic pulse (EMP) exposure on cerebral micro vascular permeability in rats. The whole-body of male Sprague-Dawley rats were exposed or sham exposed to 200 pulses or 400 pulses (1 Hz) of EMP at 200 kV/m. At 0.5, 1, 3, 6, and 12 h after EMP exposure, the permeability of cerebral micro vascular was detected by transmission electron microscopy and immunohistochemistry using lanthanum nitrate and endogenous albumin as vascular tracers, respectively. The lanthanum nitrate tracer was limited to the micro vascular lumen with no lanthanum nitrate or albumin tracer extravasation in control rat brain. After EMP exposure, the lanthanum nitrate ions reached the tight junction, basal lamina and pericapillary tissue. Similarly, the albumin immunopositive staining was identified in pericapillary tissue. The changes in brain micro vascular permeability were transient, the leakage of micro vascular vessels appeared at 1 h, and reached its peak at 3 h, and nearly recovered at 12 h, after EMP exposure. In addition, the leakage of micro vascular was more obvious after exposure of EMP at 400 pulses than after exposure of EMP at 200 pulses. Exposure to 200 and 400 pulses (1 Hz) of EMP at 200 kV/m can increase cerebral micro vascular permeability in rats, which is recoverable.

Regeneration of Tissues and Organs Using Autologous Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthony Atala

The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the curemore » that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the native tissue environment to ensure tissue integration, maturation, and survival. Other long-term benefits of this research are likely to be cell-based drug delivery mechanisms, intelligent biomaterials, bio-nano technologies, as well as controlled delivery using advances in materials science. The major challenges to the goal of producing tissues and organs for transplantation and reconstruction are three-fold and will form the basis for the goals of this research. These include (1) Identifying sources of autologous cells and developing methods to expand them in large number in vitro, (2) Providing vascular support for growing constructs, and (3) Developing biomaterials and bioreactor systems that mimic the native tissue environment.« less

Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration.

PubMed

Meghezi, Sébastien; Seifu, Dawit G; Bono, Nina; Unsworth, Larry; Mequanint, Kibret; Mantovani, Diego

2015-06-16

Synthetic materials are known to initiate clinical complications such as inflammation, stenosis, and infections when implanted as vascular substitutes. Collagen has been extensively used for a wide range of biomedical applications and is considered a valid alternative to synthetic materials due to its inherent biocompatibility (i.e., low antigenicity, inflammation, and cytotoxic responses). However, the limited mechanical properties and the related low hand-ability of collagen gels have hampered their use as scaffold materials for vascular tissue engineering. Therefore, the rationale behind this work was first to engineer cellularized collagen gels into a tubular-shaped geometry and second to enhance smooth muscle cells driven reorganization of collagen matrix to obtain tissues stiff enough to be handled. The strategy described here is based on the direct assembling of collagen and smooth muscle cells (construct) in a 3D cylindrical geometry with the use of a molding technique. This process requires a maturation period, during which the constructs are cultured in a bioreactor under static conditions (without applied external dynamic mechanical constraints) for 1 or 2 weeks. The "static bioreactor" provides a monitored and controlled sterile environment (pH, temperature, gas exchange, nutrient supply and waste removal) to the constructs. During culture period, thickness measurements were performed to evaluate the cells-driven remodeling of the collagen matrix, and glucose consumption and lactate production rates were measured to monitor the cells metabolic activity. Finally, mechanical and viscoelastic properties were assessed for the resulting tubular constructs. To this end, specific protocols and a focused know-how (manipulation, gripping, working in hydrated environment, and so on) were developed to characterize the engineered tissues.