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Sample records for adult tissue repair

  1. Adult stem cells and tissue repair.

    PubMed

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells. PMID:12931235

  2. Tissue repair

    PubMed Central

    2010-01-01

    As living beings that encounter every kind of traumatic event from paper cut to myocardial infarction, we must possess ways to heal damaged tissues. While some animals are able to regrow complete body parts following injury (such as the earthworm who grows a new head following bisection), humans are sadly incapable of such feats. Our means of recovery following tissue damage consists largely of repair rather than pure regeneration. Thousands of times in our lives, a meticulously scripted but unseen wound healing drama plays, with cells serving as actors, extracellular matrix as the setting and growth factors as the means of communication. This article briefly reviews the cells involved in tissue repair, their signaling and proliferation mechanisms and the function of the extracellular matrix, then presents the actors and script for the three acts of the tissue repair drama. PMID:21220961

  3. Progerin expression disrupts critical adult stem cell functions involved in tissue repair.

    PubMed

    Pacheco, Laurin Marie; Gomez, Lourdes Adriana; Dias, Janice; Ziebarth, Noel M; Howard, Guy A; Schiller, Paul C

    2014-12-01

    Vascular disease is one of the leading causes of death worldwide. Vascular repair, essential for tissue maintenance, is critically reduced during vascular disease and aging. Efficient vascular repair requires functional adult stem cells unimpaired by aging or mutation. One protein candidate for reducing stem cell?mediated vascular repair is progerin, an alternative splice variant of lamin A. Progerin results from erroneous activation of cryptic splice sites within the LMNA gene, and significantly increases during aging. Mutations triggering progerin overexpression cause the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), in which patients die at approximately 13-years of age due to atherosclerosis-induced disease. Progerin expression affects tissues rich in cells that can be derived from marrow stromal cells (MSCs. Studies using various MSC subpopulations and models have led to discrepant results. Using a well-defined, immature subpopulation of MSCs, Marrow Isolated Adult Multilineage Inducible (MIAMI) cells, we find progerin significantly disrupts expression and localization of self-renewal markers, proliferation, migration, and membrane elasticity. One potential treatment, farnesyltransferase inhibitor, ameliorates some of these effects. Our results confirm proposed progerin-induced mechanisms and suggest novel ways in which progerin disturbs critical stem cell functions collectively required for proper tissue repair, offering promising treatment targets for future therapies. PMID:25567453

  4. Progerin expression disrupts critical adult stem cell functions involved in tissue repair

    PubMed Central

    Pacheco, Laurin Marie; Gomez, Lourdes Adriana; Dias, Janice; Ziebarth, Noel M; Howard, Guy A; Schiller, Paul C

    2014-01-01

    Vascular disease is one of the leading causes of death worldwide. Vascular repair, essential for tissue maintenance, is critically reduced during vascular disease and aging. Efficient vascular repair requires functional adult stem cells unimpaired by aging or mutation. One protein candidate for reducing stem cell–mediated vascular repair is progerin, an alternative splice variant of lamin A. Progerin results from erroneous activation of cryptic splice sites within the LMNA gene, and significantly increases during aging. Mutations triggering progerin overexpression cause the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), in which patients die at approximately 13-years of age due to atherosclerosis-induced disease. Progerin expression affects tissues rich in cells that can be derived from marrow stromal cells (MSCs). Studies using various MSC subpopulations and models have led to discrepant results. Using a well-defined, immature subpopulation of MSCs, Marrow Isolated Adult Multilineage Inducible (MIAMI) cells, we find progerin significantly disrupts expression and localization of self-renewal markers, proliferation, migration, and membrane elasticity. One potential treatment, farnesyltransferase inhibitor, ameliorates some of these effects. Our results confirm proposed progerin-induced mechanisms and suggest novel ways in which progerin disturbs critical stem cell functions collectively required for proper tissue repair, offering promising treatment targets for future therapies. PMID:25567453

  5. Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

    PubMed

    Young, Henry E; Duplaa, Cecile; Katz, Ryan; Thompson, Tina; Hawkins, Kristina C; Boev, Angel N; Henson, Nicholas L; Heaton, Matthew; Sood, Rajiv; Ashley, Dennis; Stout, Christopher; Morgan, Joe H; Uchakin, Peter N; Rimando, Marylen; Long, Gypsy F; Thomas, Crystal; Yoon, Jee-In; Park, Ji Eun; Hunt, Darren J; Walsh, Nancy M; Davis, Josh C; Lightner, Joel E; Hutchings, Anna M; Murphy, Meredith L; Boswell, Elizabeth; McAbee, Jessica A; Gray, Brandon M; Piskurich, Janet; Blake, Lisa; Collins, Julie A; Moreau, Catherine; Hixson, Douglas; Bowyer, Frank P; Black, Asa C

    2005-01-01

    This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine. PMID:16202227

  6. Adult stem cells and biocompatible scaffolds as smart drug delivery tools for cardiac tissue repair.

    PubMed

    Pagliari, Stefania; Romanazzo, Sara; Mosqueira, Diogo; Pinto-do-Ó, Perpetua; Aoyagi, Takao; Forte, Giancarlo

    2013-01-01

    The contribution of adult stem cells to cardiac repair is mostly ascribed to an indirect paracrine effect, rather than to their actual engraftment and differentiation into new contractile and vascular cells. This effect consists in a direct reduction of host cell death, promotion of neovascularization, and in a "bystander effect" on local inflammation. A number of cytokines secreted by adult stem/progenitor cells has been proposed to be responsible for the consistent beneficial effect reported in the early attempts to deliver different stem cell subsets to the injured myocardium. Aiming to maximize their beneficial activity on the diseased myocardium, the genetic modification of adult stem cells to enhance and/or control the secretion of specific cytokines would turn them into active drug delivery vectors. On the other hand, engineering biocompatible scaffolds as to release paracrine factors could result in multiple advantages: (1) achieve a local controlled release of the drug of interest, thus minimizing off-target effects, (2) enhance stem cell retention in the injured area and (3) boost the beneficial paracrine effects exerted by adult stem cells on the host tissue. In the present review, a critical overview of the state-of-the-art in the modification of stem cells and the functionalization of biocompatible scaffolds to deliver beneficial soluble factors to the injured myocardium is offered. Besides the number of concerns to be addressed before a clinical application can be foreseen for such concepts, this path could translate into the generation of active scaffolds as smart cell and drug delivery systems for cardiac repair. PMID:23745554

  7. Activation of the Canonical Bone Morphogenetic Protein (BMP) Pathway during Lung Morphogenesis and Adult Lung Tissue Repair

    PubMed Central

    Sountoulidis, Alexandros; Stavropoulos, Athanasios; Giaglis, Stavros; Apostolou, Eirini; Monteiro, Rui; Chuva de Sousa Lopes, Susana M.; Chen, Huaiyong; Stripp, Barry R.; Mummery, Christine; Andreakos, Evangelos; Sideras, Paschalis

    2012-01-01

    Signaling by Bone Morphogenetic Proteins (BMP) has been implicated in early lung development, adult lung homeostasis and tissue-injury repair. However, the precise mechanism of action and the spatio-temporal pattern of BMP-signaling during these processes remains inadequately described. To address this, we have utilized a transgenic line harboring a BMP-responsive eGFP-reporter allele (BRE-eGFP) to construct the first detailed spatiotemporal map of canonical BMP-pathway activation during lung development, homeostasis and adult-lung injury repair. We demonstrate that during the pseudoglandular stage, when branching morphogenesis progresses in the developing lung, canonical BMP-pathway is active mainly in the vascular network and the sub-epithelial smooth muscle layer of the proximal airways. Activation of the BMP-pathway becomes evident in epithelial compartments only after embryonic day (E) 14.5 primarily in cells negative for epithelial-lineage markers, located in the proximal portion of the airway-tree, clusters adjacent to neuro-epithelial-bodies (NEBs) and in a substantial portion of alveolar epithelial cells. The pathway becomes activated in isolated E12.5 mesenchyme-free distal epithelial buds cultured in Matrigel suggesting that absence of reporter activity in these regions stems from a dynamic cross-talk between endoderm and mesenchyme. Epithelial cells with activated BMP-pathway are enriched in progenitors capable of forming colonies in three-dimensional Matrigel cultures. As lung morphogenesis approaches completion, eGFP-expression declines and in adult lung its expression is barely detectable. However, upon tissue-injury, either with naphthalene or bleomycin, the canonical BMP-pathways is re-activated, in bronchial or alveolar epithelial cells respectively, in a manner reminiscent to early lung development and in tissue areas where reparatory progenitor cells reside. Our studies illustrate the dynamic activation of canonical BMP-pathway during lung

  8. Scalp repair using tissue expanders.

    PubMed

    Mangubat, E Antonio

    2013-08-01

    Repair of scalp defects is often challenging, because without careful planning, excision of the defect may leave unsatisfactory cosmesis. Contemporary techniques in hair restoration surgery allow creation of natural and undetectable results, but these techniques are often unsuitable for repairing large scarred areas of hair loss. However, by using older techniques of scalp reduction and tissue expansion, excision of many large scarring defects can be accomplished. Combining older methods with modern hair restoration surgery permits the satisfactory treatment of many previously untreatable conditions. This article focuses on tissue expansion as an adjunct to repairing large scalp defects. PMID:24017990

  9. URIC ACID AND TISSUE REPAIR

    PubMed Central

    NERY, Rodrigo Araldi; KAHLOW, Barbara Stadler; SKARE, Thelma L; TABUSHI, Fernando Issamu; CASTRO, Adham do Amaral e

    2015-01-01

    Uric acid, a metabolic product of purines, may exert a role in tissue healing. In this review we will explore its role as an alarm initiating the inflammatory process that is necessary for tissue repair, as a scavenger of oxygen free radicals, as a mobilizer of progenitor endothelial cells and as supporter of adaptive immune system. PMID:26734804

  10. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  11. Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.

    PubMed

    Goichberg, Polina

    2016-08-01

    With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential. PMID:27209167

  12. [Tissue engineered skin and regenerative wound repair].

    PubMed

    Han, Chun-mao; Wang, Xin-gang

    2013-04-01

    Various skin defects resulting from mechanical injury, burns, chronic ulcers, and resection of tumor etc. are very common in clinic. The traditional treatment measure, such as grafting of autologous split-thickness skin remains the gold standard. However, its limitations are obvious, such as shortage of donor sites, creation of new injury, and scar formation. To realize regenerative or scarless repair of tissue defects has always been the dream of human being. The advent of tissue engineered skin (TES) provides an ideal access to tissue regeneration. After decades of development, several kinds of TES products have been developed and used in clinic, with promising effects. However, a large number of basic scientific problems regarding TES, as well as difficulties in translation of basic research to bedside should be taken into serious consideration. This article presents a comprehensive overview of strategies of construction of TES, the role of TES in regenerative wound repair, and its opportunities and challenges. PMID:23985197

  13. Native Tissue Prolapse Repairs: Comparative Effectiveness Trials.

    PubMed

    Siff, Lauren N; Barber, Matthew D

    2016-03-01

    This report reviews the success rates and complications of native tissue (nonmesh) vaginal reconstruction of pelvic organ prolapse by compartment. For apical prolapse, both uterosacral ligament suspensions and sacrospinous ligament fixations are effective and provided similar outcomes in anatomy and function with few adverse events. In the anterior compartment, traditional colporrhaphy technique is no different than ultralateral suturing. In the posterior compartment, transvaginal rectocele repair is superior to transanal repair. For uterine preservation, sacrospinous hysteropexy is not inferior to vaginal hysterectomy with uterosacral ligament suspension for treatment of apical uterovaginal prolapse. PMID:26880509

  14. Myocardial tissue engineering for cardiac repair.

    PubMed

    Pecha, Simon; Eschenhagen, Thomas; Reichenspurner, Hermann

    2016-03-01

    The number of patients with heart failure is increasing in the aging population. Heart transplantation remains the only curative treatment option for patients with end-stage heart failure. Because of an organ donor shortage, new organ-independent treatment options are necessary. Different approaches to cardiac repair therapies have been developed and optimized in recent years. One of these promising approaches is myocardial tissue engineering, which refers to the creation of 3-dimensional engineered heart tissue in vitro. This perspective provides an overview of different approaches to tissue engineering, including essentials to improve tissue quality and choice of ideal cell source, as well as an overview of in vitro and in vivo studies. Several hurdles that have to be overcome before clinical application of engineered heart tissue might become a realistic scenario are also addressed. PMID:26856673

  15. Mesenchymal Stem Cells in Tissue Growth and Repair

    PubMed Central

    Kalinina, N.I.; Sysoeva, V.Yu.; Rubina, K.A.; Parfenova, Ye.V.; Tkachuk, V.A.

    2011-01-01

    It has been established in the recent several decades that stem cells play a crucial role in tissue renewal and regeneration. Mesenchymal stem cells (MSCs) are part of the most important population of adult stem cells. These cells have hereby been identified for the very first time and subsequently isolated from bone marrow stroma. Bone marrow-derived MSCs have been believed to play the role of a source of cells for the renewal and repair of connective tissues, including bone, cartilage and adipose tissues. Cells similar to bone marrow-derived MSCs have now been identified in all postnatal tissues. Data on the distribution and function of MSCsin vivocollected using novel approaches pertaining to the identification of MSCsin situ, to their isolation from tissues, and finally to the determination of their biological properties have enabled successful revision of the role of MSCs in various organs and tissues. This review summarizes our own, as well as others’, data concerning the role of MSCs in the regulation processes of tissue repair and regeneration. In our opinion, MSCs provide the connection between the blood-vascular, immune, endocrine, and nervous systems and tissue-specific stem cells in the body. PMID:22649702

  16. Tissue Engineering and Regenerative Repair in Wound Healing

    PubMed Central

    Hu, Michael S.; Maan, Zeshaan N.; Wu, Jen-Chieh; Rennert, Robert C.; Hong, Wan Xing; Lai, Tiffany S.; Cheung, Alexander T. M.; Walmsley, Graham G.; Chung, Michael T.; McArdle, Adrian; Longaker, Michael T.; Lorenz, H. Peter

    2014-01-01

    Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration. PMID:24788648

  17. Increased Production of Clusterin in Biopsies of Repair Tissue following Autologous Chondrocyte Implantation

    PubMed Central

    Malda, Jos; Richardson, James B.; Roberts, Sally

    2013-01-01

    Objective. To characterize the immunolocalization of clusterin in the repair cartilage of patients having undergone autologous chondrocyte implantation (ACI) and evaluate correlation to clinical outcome. Design. Full-depth core biopsies of repair tissue were obtained from 38 patients who had undergone ACI at an average of 18 ± 13 months previously (range 8-67 months). The biopsies were snap frozen, cryosectioned, and clusterin production immunolocalized using a specific monoclonal clusterin antibody and compared with normal and osteoarthritic cartilage. Clinical outcome was assessed from patients preoperatively, at the time of biopsy, and annually postoperatively. Results. Intensity of immunostaining for clusterin decreased with age in healthy cartilage tissue. Clusterin was detected to a variable degree in 37 of the 38 ACI cartilage biopsies, in single and clustered chondrocytes, in the pericellular capsule and the cartilage extracellular matrix, as well as the osteocytes and osteoid within the bone. Chondrocytes in hyaline repair tissue were significantly more immunopositive than those in fibrocartilage repair tissue. Clinical outcome improved significantly post-ACI, but did not correlate with the presence of clusterin in the repair tissue. Conclusions. These results demonstrate the presence of clusterin in actively repairing human cartilage and indicate a different distribution of clusterin in this tissue compared to normal cartilage. Variability in clusterin staining in the repair tissue could indicate different states of chondrogenic differentiation. The clinical significance of clusterin within repair tissue is difficult to assess, although the ideal functioning repair tissue morphology should resemble that of healthy adult cartilage. PMID:26069669

  18. Cell-based and biomaterial approaches to connective tissue repair

    NASA Astrophysics Data System (ADS)

    Stalling, Simone Suzette

    Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

  19. Mesothelial cells in tissue repair and fibrosis

    PubMed Central

    Mutsaers, Steven E.; Birnie, Kimberly; Lansley, Sally; Herrick, Sarah E.; Lim, Chuan-Bian; Prêle, Cecilia M.

    2015-01-01

    Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis. In addition to secreting proinflammatory mediators and contributing to both coagulation and fibrinolysis, mesothelial cells undergo mesothelial-to-mesenchymal transition, a process analogous to epithelial-to-mesenchymal transition, and become fibrogenic cells. Fibrogenic mesothelial cells have now been identified in tissues where they have not previously been thought to occur, such as within the parenchyma of the fibrotic lung. These findings show a direct role for mesothelial cells in fibrogenesis and open therapeutic strategies to prevent or reverse the fibrotic process. PMID:26106328

  20. Adult soft tissue sarcoma

    MedlinePlus

    ... free at 5 years. Most people who survive 5 years can expect to be cancer-free at 10 years. ... most soft tissue sarcomas, and there is no way to prevent it. ... them can increase your chance of surviving this type of cancer.

  1. Apparatus for enhancing tissue repair in mammals

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2007-01-01

    An apparatus is disclosed for enhancing tissue repair in mammals, with the apparatus comprising: a sleeve for encircling a portion of a mammalian body part, said sleeve comprising an electrically conductive coil capable of generating an electromagnetic field when an electrical current is applied thereto, means for supporting the sleeve on the mammalian body part; and means for supplying the electrically conductive coil with a square wave time varying electrical current sufficient to create a time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss within the interior of the coil in order that when the sleeve is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss is generated on the mammalian body part for an extended period of time, tissue regeneration within the mammalian body part is increased to a rate in excess of the normal tissue regeneration rate that would occur without application of the time varying electromagnetic force.

  2. General Information about Adult Soft Tissue Sarcoma

    MedlinePlus

    ... Soft Tissue Sarcoma Treatment (PDQ®)–Patient Version General Information About Adult Soft Tissue Sarcoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. Optimisation of the biology of soft tissue repair.

    PubMed

    Frank, C; Shrive, N; Hiraoka, H; Nakamura, N; Kaneda, Y; Hart, D

    1999-10-01

    As identified in this review, over the past twenty years there have been a number of very exciting new developments in the quest to optimise soft tissue repair. Comparing fetal soft tissue injuries, which heal by regeneration, to the adult processes of healing by inflammation-induced scar formation has led to a number of insights into how the latter may be improved. Seeding wounds with embryonic stem cells, bridging gaps with cell-derived "engineered tissues", addition of exogenous hyaluronic acid and modification of wounds to either enhance the growth factors which have been implicated in regeneration (e.g. TGF-B3) or block those implicated in scar formation (eg. TGF-B1) have all shown promise. Our group has quantified numerous cellular, molecular, biomechanical and matrix abnormalities of scar in a rabbit model of ligament healing. Based on these studies which we review here, three matrix deficiencies have been identified which appear to have specific implications to scar weakness: organisational "flaws", abnormal hydroxypyridinoline collagen cross-link densities and abnormally small, slow-maturing collagen fibrils. In tests aimed at finding therapeutic solutions in this model, the addition of a 7ug bolus of TGF-B1 at day 21 or 2.5ng/day of TGF-B1 being pumped into a wound x 21 days increased the size of ligament scars but did not improve their material strength. It also did not alter any of the above-noted matrix deficiencies. A liposome-mediated anti-sense gene therapy approach aimed at decreasing the expression of the proteoglycan decorin in 21-day scars, however, has significantly increased the size of scar collagen fibrils as well as improved these scars mechanically. Based on these positive results from a single dose of only one targeted molecule, we believe that this gene therapy approach has great potential for further scar improvement. If combined with some of the other biological strategies reviewed above, a repair which is closer to true regenerative

  4. Macrophage plasticity and polarization in tissue repair and remodelling.

    PubMed

    Mantovani, Alberto; Biswas, Subhra K; Galdiero, Maria Rosaria; Sica, Antonio; Locati, Massimo

    2013-01-01

    Mononuclear phagocyte plasticity includes the expression of functions related to the resolution of inflammation, tissue repair and remodelling, particularly when these cells are set in an M2 or an M2-like activation mode. Macrophages are credited with an essential role in remodelling during ontogenesis. In extraembryonic life, under homeostatic conditions, the macrophage trophic and remodelling functions are recapitulated in tissues such as bone, mammary gland, decidua and placenta. In pathology, macrophages are key components of tissue repair and remodelling that occur during wound healing, allergy, parasite infection and cancer. Interaction with cells bearing stem or progenitor cell properties is likely an important component of the role of macrophages in repair and remodelling. These properties of cells of the monocyte-macrophage lineage may represent a tool and a target for therapeutic exploitation. PMID:23096265

  5. Biomaterial applications in cardiovascular tissue repair and regeneration

    PubMed Central

    Lam, Mai T; Wu, Joseph C

    2013-01-01

    Cardiovascular disease physically damages the heart, resulting in loss of cardiac function. Medications can help alleviate symptoms, but it is more beneficial to treat the root cause by repairing injured tissues, which gives patients better outcomes. Besides heart transplants, cardiac surgeons use a variety of methods for repairing different areas of the heart such as the ventricular septal wall and valves. A multitude of biomaterials are used in the repair and replacement of impaired heart tissues. These biomaterials fall into two main categories: synthetic and natural. Synthetic materials used in cardiovascular applications include polymers and metals. Natural materials are derived from biological sources such as human donor or harvested animal tissues. A new class of composite materials has emerged to take advantage of the benefits of the strengths and minimize the weaknesses of both synthetic and natural materials. This article reviews the current and prospective applications of biomaterials in cardiovascular therapies. PMID:23030293

  6. Fibrocytes and the tissue niche in lung repair.

    PubMed

    Andersson-Sjöland, Annika; Nihlberg, Kristian; Eriksson, Leif; Bjermer, Leif; Westergren-Thorsson, Gunilla

    2011-01-01

    Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases. PMID:21658209

  7. The 23rd Annual Meeting of the European Tissue Repair Society (ETRS) in Reims, France

    PubMed Central

    2014-01-01

    The 23rd Annual Meeting of the European Tissue Repair Society, Reims, France, October 23 to 25, 2013 focused on tissue repair and regenerative medicine covering topics such as stem cells, biomaterials, tissue engineering, and burns. PMID:24552134

  8. Repair of Dense Connective Tissues via Biomaterial-Mediated Matrix Reprogramming of the Wound Interface

    PubMed Central

    Qu, Feini; Pintauro, Michael P.; Haughan, Joanne; Henning, Elizabeth A.; Esterhai, John L.; Schaer, Thomas P.; Mauck, Robert L.; Fisher, Matthew B.

    2014-01-01

    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. PMID:25477175

  9. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

    PubMed

    Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

    2015-01-01

    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. PMID:25477175

  10. Stem cell-derived angiogenic/vasculogenic cells: possible therapies for tissue repair and tissue engineering.

    PubMed

    Zwaginga, J J; Doevendans, P

    2003-11-01

    1. The recent ability to isolate stem cells and study their specific capacity of self-renewal with the formation of different cell types has opened up exciting vistas to help the repair of damaged tissue and even the formation of new tissue. In the present review, we deal with the characteristics and sources that stem cells can be derived and cultured from. 2. We focus on the role that stem cell-derived vascular cells or endothelial progenitor cells (EPC) may play in (re)vascularization of ischaemic and engineered tissues. This so-called vasculogenesis resembles the embryological process in which 'haemangioblasts' differentiate in blood cells, as well as in primitive vessels. Although also derived from the blood-forming bone marrow, in adult life vasculogenic stem cells contribute only little to the regular vascular repair mechanisms: namely (i) angiogenesis (outgrowth of vessels from existing vessels); and (ii) arteriogenesis (monocyte-aided increase in the calibre of existing arteriolar collaterals). 3. Most attempts to increase vascular repair by stem cells involve the use of growth factors, which mobilize stem cells from bone marrow into the blood, sometimes combined with isolation and reinfusion of these cells after ex vivo expansion and differentiation into EPC. 4. Clear improved perfusion of ischaemic sites and new vasculature has been observed in vivo mostly in animal models. Specific homing or administration of these cells and regulated and quantitative expansion and (final) differentiation at these vascular (repair) sites are less studied, but are paramount for efficacy and safety. 5. In conclusion, the use of embryonic stem cells will still encounter ethical objections. Moreover, special attention and measures are needed to cope with the allogeneic barriers that these cells usually encounter. In general, the long and complicated ex vivo cultures to obtain sufficient offspring from the very small numbers of stem cells that can be obtained as starting

  11. Host Responses in Tissue Repair and Fibrosis

    PubMed Central

    Duffield, Jeremy S.; Lupher, Mark; Thannickal, Victor J.

    2013-01-01

    Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary “effector” cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis. PMID:23092186

  12. Adult stem cell lineage tracing and deep tissue imaging

    PubMed Central

    Fink, Juergen; Andersson-Rolf, Amanda; Koo, Bon-Kyoung

    2015-01-01

    Lineage tracing is a widely used method for understanding cellular dynamics in multicellular organisms during processes such as development, adult tissue maintenance, injury repair and tumorigenesis. Advances in tracing or tracking methods, from light microscopy-based live cell tracking to fluorescent label-tracing with two-photon microscopy, together with emerging tissue clearing strategies and intravital imaging approaches have enabled scientists to decipher adult stem and progenitor cell properties in various tissues and in a wide variety of biological processes. Although technical advances have enabled time-controlled genetic labeling and simultaneous live imaging, a number of obstacles still need to be overcome. In this review, we aim to provide an in-depth description of the traditional use of lineage tracing as well as current strategies and upcoming new methods of labeling and imaging. [BMB Reports 2015; 48(12): 655-667] PMID:26634741

  13. Micro- and Nanostructured Biomaterials for Sutureless Tissue Repair.

    PubMed

    Frost, Samuel J; Mawad, D; Hook, J; Lauto, Antonio

    2016-02-18

    Sutureless procedures for wound repair and closure have recently integrated nanostructured devices to improve their effectiveness and clinical outcome. This review highlights the major advances in gecko-inspired bioadhesives that relies mostly on van der Waals bonding forces. These are challenged by the moist environment of surgical settings that weaken adherence to tissue. The incorporation of nanoparticles in biomatrices and their role in tissue repair and drug delivery is also reviewed with an emphasis on procedures involving adhesives that are laser-activated. Nanostructured adhesive devices have the advantage of being minimally invasive to tissue, can seal wounds, and deliver drugs in situ. All these tasks are very difficult to accomplish by sutures or staples that are invasive to host organs and often cause scarring. PMID:26725593

  14. Tissue engineering using adult stem cells.

    PubMed

    Eberli, Daniel; Atala, Anthony

    2006-01-01

    Patients with a variety of diseases may be treated with transplanted tissues and organs. However, there is a shortage of donor tissues and organs, which is worsening yearly because of the aging population. Scientists in the field of tissue engineering are applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new options for cellular therapy and tissue engineering. The use of adult stem cells for tissue engineering applications is promising. This chapter discusses applications of these new technologies for the engineering of tissues and organs. The first part provides an overview of regenerative medicine and tissue engineering techniques; the second highlights different adult stem cell populations used for tissue regeneration. PMID:17161702

  15. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation

    PubMed Central

    O'Connell, Grace D.; Leach, J. Kent; Klineberg, Eric O.

    2015-01-01

    Abstract The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  16. A normal tissue dose response model of dynamic repair processes

    NASA Astrophysics Data System (ADS)

    Alber, Markus; Belka, Claus

    2006-01-01

    A model is presented for serial, critical element complication mechanisms for irradiated volumes from length scales of a few millimetres up to the entire organ. The central element of the model is the description of radiation complication as the failure of a dynamic repair process. The nature of the repair process is seen as reestablishing the structural organization of the tissue, rather than mere replenishment of lost cells. The interactions between the cells, such as migration, involved in the repair process are assumed to have finite ranges, which limits the repair capacity and is the defining property of a finite-sized reconstruction unit. Since the details of the repair processes are largely unknown, the development aims to make the most general assumptions about them. The model employs analogies and methods from thermodynamics and statistical physics. An explicit analytical form of the dose response of the reconstruction unit for total, partial and inhomogeneous irradiation is derived. The use of the model is demonstrated with data from animal spinal cord experiments and clinical data about heart, lung and rectum. The three-parameter model lends a new perspective to the equivalent uniform dose formalism and the established serial and parallel complication models. Its implications for dose optimization are discussed.

  17. New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

    PubMed Central

    Musumeci, Giuseppe; Castrogiovanni, Paola; Leonardi, Rosalia; Trovato, Francesca Maria; Szychlinska, Marta Anna; Di Giunta, Angelo; Loreto, Carla; Castorina, Sergio

    2014-01-01

    In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis. PMID:24829869

  18. HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR

    PubMed Central

    Zhu, Suwei; Segura, Tatiana

    2014-01-01

    The ability to design artificial extracellular matrices as cell instructive scaffolds has opened the door to technologies capable of studying cell fates in vitro and to guide tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of protein-based biochemical cues to guide cell phenotypes and multicellular organizations. However, promoting the long-term bioactivity, controlling the bioavailability and understanding how the physical presentations of these proteins impacts cellular fates are among the challenges of the field. Nanotechnolgy has advanced to meet the challenges of protein therapeutics. For example, the approaches to incorporating proteins into tissue repairing scaffolds have ranged from bulk encapsulations to smart nanodepots that protect proteins from degradations and allow opportunities for controlled release. PMID:24778979

  19. Laparoscopic repair of a Bochdalek hernia in an adult woman.

    PubMed

    Sutedja, Barlian; Muliani, Yenny

    2015-08-01

    Bochdalek hernia (BH) is a congenital defect of the diaphragm that usually presents in the neonatal period with life threatening cardiorespiratory distress. It is rare for BH to remain silent until adulthood. A 51-year-old woman presented with progressive dyspnea and abdominal symptoms, but without a history of trauma. The diagnosis of BH was made based on chest X-ray and CT. The hernia was repaired by the laparoscopic technique, and the patient made an uneventful recovery. This report validates the feasibility of laparoscopic repair of BH in an adult, which should be within the capability of an advanced laparoscopic surgeon. PMID:26303737

  20. Materials Science and Tissue Engineering: Repairing the Heart

    PubMed Central

    Radisic, Milica; Christman, Karen L.

    2013-01-01

    Heart failure following a myocardial infarction continues to be a leading killer in the western world. Currently there are no therapies that effectively prevent or reverse the cardiac damage and negative left ventricular remodeling process that follows a myocardial infarction. Since the heart has limited regenerative capacity, there has been significant effort to develop new therapies that could repair and regenerate the myocardium. While cell transplantation alone was initially studied, more recently tissue engineering strategies using biomaterial scaffolds have been explored. In this review, we cover the different approaches to engineer the myocardium. These include cardiac patches, which are in vitro engineered constructs of functional myocardium, as well as injectable scaffolds that can either encourage endogenous repair and regeneration, or act as vehicles to support delivery of cells and other therapeutics. PMID:23910415

  1. Apparatus and method for enhancing tissue repair in mammals

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2009-01-01

    An apparatus is introduced for the use of enhancing tissue repair in mammals. The apparatus includes a sleeve; an electrically conductive coil; a sleeve support; an electrical circuit configured to supply the coil with a square wave time varying electrical current sufficient to create approximately 0.05 gauss to 0.5 gauss. When in use, the sleeve of the apparatus is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.5 gauss is generated on the mammalian body for an extended period of time so that the tissue is encouraged to be regenerated in the mammalian body part at a rate in excess of the normal tissue regeneration rate relative to regeneration without application of the time varying electromagnetic force.

  2. Wound-Induced Polyploidy Is Required for Tissue Repair

    PubMed Central

    Losick, Vicki P.

    2016-01-01

    Significance: All organs suffer wounds to some extent during an animal's lifetime and to compensate for cell loss, tissues often rely on cell division. However, many organs are made up of differentiated cells with only a limited capacity to divide. It is not well understood how cells are replaced in the absence of cell division. Recent Advances: Recent studies in the model organism Drosophila melanogaster have proven that wound-induced polyploidy (WIP) is an essential mechanism to replace tissue mass and restore tissue integrity in the absence of cell division. In this repair mechanism, preexisting differentiated cells increase their DNA content and cell size by becoming polyploid. Critical Issues: Cells within mammalian organs such as the liver, heart, and cornea have also been observed to increase their DNA ploidy in response to injury, suggesting that WIP may be an evolutionarily conserved mechanism to compensate for cell loss. Future Directions: The Hippo signal transduction pathway is required for differentiated cells to initiate WIP in Drosophila. Continued studies in Drosophila will help to identify other signaling pathways required for WIP as well as the conserved mechanisms that polyploid cells may play during wound repair in all organisms. PMID:27274437

  3. Use of NASA Bioreactor in Engineering Tissue for Bone Repair

    NASA Technical Reports Server (NTRS)

    Duke, Pauline

    1998-01-01

    This study was proposed in search for a new alternative for bone replacement or repair. Because the systems commonly used in repair of bony defects form bone by going through a cartilaginous phase, implantation of a piece of cartilage could enhance the healing process by having a more advanced starting point. However, cartilage has seldom been used to replace bone due, in part, to the limitations in conventional culture systems that did not allow production of enough tissue for implants. The NASA-developed bioreactors known as STLV (Slow Turning Lateral Vessel) provide homogeneous distribution of cells, nutrients, and waste products, with less damaging turbulence and shear forces than conventional systems. Cultures under these conditions have higher growth rates, viability, and longevity, allowing larger "tissue-like" aggregates to form, thus opening the possibilities of producing enough tissue for implantation, along with the inherent advantages of in vitro manipulations. To assure large numbers of cells and to eliminate the use of timed embryos, we proposed to use an immortalized mouse limb bud cell line as the source of cells.

  4. Pleural tissue repair with cord blood platelet gel

    PubMed Central

    Rosso, Lorenzo; Parazzi, Valentina; Damarco, Francesco; Righi, Ilaria; Santambrogio, Luigi; Rebulla, Paolo; Gatti, Stefano; Ferrero, Stefano; Nosotti, Mario; Lazzari, Lorenza

    2014-01-01

    Background Prolonged air leak is the major cause of morbidity after pulmonary resection. In this study we used in vitro and in vivo experiments to investigate an innovative approach based on the use of human umbilical cord blood platelet gel. Materials and methods In vitro, a scratch assay was performed to test the tissue repair capability mediated by cord blood platelet gel compared to the standard culture conditions using human primary mesothelial cells. In vivo, an iatrogenic injury was made to the left lung of 54 Wistar rats. Cord blood platelet gel was placed on the injured area only in treated animals and at different times histological changes and the presence of pleural adhesions were evaluated. In addition, changes in the pattern of soluble inflammatory factors were investigated using a multiplex proteome array. Results In vitro, mesothelial cell damage was repaired in a shorter time by cord blood platelet gel than in the control condition (24 versus 35 hours, respectively). In vivo, formation of new mesothelial tissue and complete tissue recovery were observed at 45±1 and 75±1 hours in treated animals and at 130±2.5 and 160±6 hours in controls, respectively. Pleural adhesions were evident in 43% of treated animals compared to 17% of controls. No complications were observed. Interestingly, some crucial soluble factors involved in inflammation were significantly reduced in treated animals. Discussion Cord blood platelet gel accelerates the repair of pleural damage and stimulates the development of pleural adhesions. Both properties could be particularly useful in the management of prolonged air leak, and to reduce inflammation. PMID:23736928

  5. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  6. Cellular forces and matrix assembly coordinate fibrous tissue repair

    PubMed Central

    Sakar, Mahmut Selman; Eyckmans, Jeroen; Pieters, Roel; Eberli, Daniel; Nelson, Bradley J.; Chen, Christopher S.

    2016-01-01

    Planar in vitro models have been invaluable tools to identify the mechanical basis of wound closure. Although these models may recapitulate closure dynamics of epithelial cell sheets, they fail to capture how a wounded fibrous tissue rebuilds its 3D architecture. Here we develop a 3D biomimetic model for soft tissue repair and demonstrate that fibroblasts ensconced in a collagen matrix rapidly close microsurgically induced defects within 24 h. Traction force microscopy and time-lapse imaging reveal that closure of gaps begins with contractility-mediated whole-tissue deformations. Subsequently, tangentially migrating fibroblasts along the wound edge tow and assemble a progressively thickening fibronectin template inside the gap that provide the substrate for cells to complete closure. Unlike previously reported mechanisms based on lamellipodial protrusions and purse-string contraction, our data reveal a mode of stromal closure in which coordination of tissue-scale deformations, matrix assembly and cell migration act together to restore 3D tissue architecture. PMID:26980715

  7. Cellular forces and matrix assembly coordinate fibrous tissue repair.

    PubMed

    Sakar, Mahmut Selman; Eyckmans, Jeroen; Pieters, Roel; Eberli, Daniel; Nelson, Bradley J; Chen, Christopher S

    2016-01-01

    Planar in vitro models have been invaluable tools to identify the mechanical basis of wound closure. Although these models may recapitulate closure dynamics of epithelial cell sheets, they fail to capture how a wounded fibrous tissue rebuilds its 3D architecture. Here we develop a 3D biomimetic model for soft tissue repair and demonstrate that fibroblasts ensconced in a collagen matrix rapidly close microsurgically induced defects within 24 h. Traction force microscopy and time-lapse imaging reveal that closure of gaps begins with contractility-mediated whole-tissue deformations. Subsequently, tangentially migrating fibroblasts along the wound edge tow and assemble a progressively thickening fibronectin template inside the gap that provide the substrate for cells to complete closure. Unlike previously reported mechanisms based on lamellipodial protrusions and purse-string contraction, our data reveal a mode of stromal closure in which coordination of tissue-scale deformations, matrix assembly and cell migration act together to restore 3D tissue architecture. PMID:26980715

  8. Method of tissue repair using a composite material

    DOEpatents

    Hutchens, Stacy A; Woodward, Jonathan; Evans, Barbara R; O'Neill, Hugh M

    2014-03-18

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  9. Method of tissue repair using a composite material

    DOEpatents

    Hutchens, Stacy A.; Woodward, Jonathan; Evans, Barbara R.; O'Neill, Hugh M.

    2016-03-01

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  10. Adult human neural crest-derived cells for articular cartilage repair.

    PubMed

    Pelttari, Karoliina; Pippenger, Benjamin; Mumme, Marcus; Feliciano, Sandra; Scotti, Celeste; Mainil-Varlet, Pierre; Procino, Alfredo; von Rechenberg, Brigitte; Schwamborn, Thomas; Jakob, Marcel; Cillo, Clemente; Barbero, Andrea; Martin, Ivan

    2014-08-27

    In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions. PMID:25163479

  11. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    PubMed

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26801961

  12. Fibroblast growth factors as tissue repair and regeneration therapeutics.

    PubMed

    Nunes, Quentin M; Li, Yong; Sun, Changye; Kinnunen, Tarja K; Fernig, David G

    2016-01-01

    Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West. PMID:26793421

  13. Fibroblast growth factors as tissue repair and regeneration therapeutics

    PubMed Central

    Kinnunen, Tarja K.

    2016-01-01

    Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West. PMID:26793421

  14. Parthenogenetic stem cells for tissue-engineered heart repair

    PubMed Central

    Didié, Michael; Christalla, Peter; Rubart, Michael; Muppala, Vijayakumar; Döker, Stephan; Unsöld, Bernhard; El-Armouche, Ali; Rau, Thomas; Eschenhagen, Thomas; Schwoerer, Alexander P.; Ehmke, Heimo; Schumacher, Udo; Fuchs, Sigrid; Lange, Claudia; Becker, Alexander; Tao, Wen; Scherschel, John A.; Soonpaa, Mark H.; Yang, Tao; Lin, Qiong; Zenke, Martin; Han, Dong-Wook; Schöler, Hans R.; Rudolph, Cornelia; Steinemann, Doris; Schlegelberger, Brigitte; Kattman, Steve; Witty, Alec; Keller, Gordon; Field, Loren J.; Zimmermann, Wolfram-Hubertus

    2013-01-01

    Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair. PMID:23434590

  15. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds

    PubMed Central

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D.

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  16. S100B protein in tissue development, repair and regeneration

    PubMed Central

    Sorci, Guglielmo; Riuzzi, Francesca; Arcuri, Cataldo; Tubaro, Claudia; Bianchi, Roberta; Giambanco, Ileana; Donato, Rosario

    2013-01-01

    The Ca2+-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular regulatory activities. As an intracellular regulator, S100B is involved in the regulation of energy metabolism, transcription, protein phosphorylation, cell proliferation, survival, differentiation and motility, and Ca2+ homeostasis, by interacting with a wide array of proteins (i.e., enzymes, enzyme substrates, cytoskeletal subunits, scaffold/adaptor proteins, transcription factors, ubiquitin E3 ligases, ion channels) in a restricted number of cell types. As an extracellular signal, S100B engages the pattern recognition receptor, receptor for advanced glycation end-products (RAGE), on immune cells as well as on neuronal, astrocytic and microglial cells, vascular smooth muscle cells, skeletal myoblasts and cardiomyocytes. However, RAGE may not be the sole receptor activated by S100B, the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types. Moreover, extracellular effects of S100B vary depending on its local concentration. Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury, which is up to a few nM levels, S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis. The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development, repair and regeneration. PMID:23580916

  17. Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures.

    PubMed

    Uhl, Franziska E; Vierkotten, Sarah; Wagner, Darcy E; Burgstaller, Gerald; Costa, Rita; Koch, Ina; Lindner, Michael; Meiners, Silke; Eickelberg, Oliver; Königshoff, Melanie

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of lung tissue. Inducing repair processes within the adult diseased lung is of major interest and Wnt/β-catenin signalling represents a promising target for lung repair. However, the translation of novel therapeutic targets from model systems into clinical use remains a major challenge.We generated murine and patient-derived three-dimensional (3D) ex vivo lung tissue cultures (LTCs), which closely mimic the 3D lung microenvironment in vivo. Using two well-known glycogen synthase kinase-3β inhibitors, lithium chloride (LiCl) and CHIR 99021 (CT), we determined Wnt/β-catenin-driven lung repair processes in high spatiotemporal resolution using quantitative PCR, Western blotting, ELISA, (immuno)histological assessment, and four-dimensional confocal live tissue imaging.Viable 3D-LTCs exhibited preserved lung structure and function for up to 5 days. We demonstrate successful Wnt/β-catenin signal activation in murine and patient-derived 3D-LTCs from COPD patients. Wnt/β-catenin signalling led to increased alveolar epithelial cell marker expression, decreased matrix metalloproteinase-12 expression, as well as altered macrophage activity and elastin remodelling. Importantly, induction of surfactant protein C significantly correlated with disease stage (per cent predicted forced expiratory volume in 1 s) in patient-derived 3D-LTCs.Patient-derived 3D-LTCs represent a valuable tool to analyse potential targets and drugs for lung repair. Enhanced Wnt/β-catenin signalling attenuated pathological features of patient-derived COPD 3D-LTCs. PMID:25929950

  18. [Endovascular repair for coarctation of the aorta in an adult].

    PubMed

    Hayashi, Jun; Abe, Kazuo; Hata, Masaki; Nagano, Naoko; Hamasaki, Azumi; Suzuki, Kenji

    2013-09-01

    A 27-year-old woman with Turner's syndrome who underwent successful endovascular treatment for coarctation of the aorta is presented. She was admitted to our hospital complaining of upper extremity hypertension. Computed tomography revealed discrete stenosis of the proximal descending aorta and developed collateral circulation. After endovascular repair with a balloon expandable stent, her transcoarctation gradient fell from 44 mmHg preoperatively to less than 10 mmHg. She was discharged with no complications on the 7th postoperative day. Coarctation of the aorta in an adult patient could be safely and effectively managed by endovascular treatment. PMID:24008641

  19. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair.

    PubMed

    Gnecchi, Massimiliano; Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara

    2016-01-01

    Tissue regeneration from transplanted mesenchymal stromal cells (MSC) either through transdifferentiation or cell fusion was originally proposed as the principal mechanism underlying their therapeutic action. However, several studies have now shown that both these mechanisms are very inefficient. The low MSC engraftment rate documented in injured areas also refutes the hypothesis that MSC repair tissue damage by replacing cell loss with newly differentiated cells. Indeed, despite evidence of preferential homing of MSC to the site of myocardial ischemia, exogenously administered MSC show poor survival and do not persist in the infarcted area. Therefore, it has been proposed that the functional benefits observed after MSC transplantation in experimental models of tissue injury might be related to the secretion of soluble factors acting in a paracrine fashion. This hypothesis is supported by pre-clinical studies demonstrating equal or even improved organ function upon infusion of MSC-derived conditioned medium (MSC-CM) compared with MSC transplantation. Identifying key MSC-secreted factors and their functional role seems a reasonable approach for a rational design of nextgeneration MSC-based therapeutics. Here, we summarize the major findings regarding both different MSC-mediated paracrine actions and the identification of paracrine mediators. PMID:27236669

  20. Advances and Perspectives on Tissue Repair and Healing

    NASA Astrophysics Data System (ADS)

    Pinheiro, Antonio L. B.; Marques, Aparecida M. C.; de Sousa, Ana Paula C.; Aciole, Jouber M. S.; Soares, Luiz G. P.

    2011-08-01

    Wound healing involves local and systemic responses that reflect the etiology of the lesion, type of tissue, systemic condition and others. Despite being essentially the same for different wounds, the pattern of healing may change due to intrinsic and/or extrinsic factors. The type of tissue has also to be considered. Several therapeutic approaches have been used to improve healing including phototherapies such as Laser, LEDs and Lamps. Their effects on soft and mineralized tissues are well reported. The choice of appropriated parameters is essential for the results of the treatment and includes wavelength, power density, energy, duration and frequency of application and others. We studied the effects of different types of light on the healing of both soft and mineralized tissues using different models. We found that the use of Laser and polarized light are effective on improving the healing of diabetic and undernourished animals. We also found that Laser light is capable of improving the healing of drug-induced impairment and on increasing the survival rate of flaps on both diabetic and non-diabetic animals. We have also studied and shown the influence of the laser parameters on the healing of surgical and laser wounds. Lately we verified the positive effect of LEDs on healing. We used Laser/LED light for improving bone healing in conditions such as in dental implants, autologous grafts, biomaterials and fractures. From these reports and our own experience we have no doubt whatsoever that the use of phototherapies, carried out with appropriate parameters, promotes quicker tissue repair.

  1. How Somatic Adult Tissues Develop Organizer Activity.

    PubMed

    Vogg, Matthias C; Wenger, Yvan; Galliot, Brigitte

    2016-01-01

    The growth and patterning of anatomical structures from specific cellular fields in developing organisms relies on organizing centers that instruct surrounding cells to modify their behavior, namely migration, proliferation, and differentiation. We discuss here how organizers can form in adult organisms, a process of utmost interest for regenerative medicine. Animals like Hydra and planarians, which maintain their shape and fitness thanks to a highly dynamic homeostasis, offer a useful paradigm to study adult organizers in steady-state conditions. Beside the homeostatic context, these model systems also offer the possibility to study how organizers form de novo from somatic adult tissues. Both extracellular matrix remodeling and caspase activation play a key role in this transition, acting as promoters of organizer formation in the vicinity of the wound. Their respective roles and the crosstalk between them just start to be deciphered. PMID:26970630

  2. Repair and tissue engineering techniques for articular cartilage

    PubMed Central

    Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

  3. Recombinant gelatin microspheres: novel formulations for tissue repair?

    PubMed

    Tuin, Annemarie; Kluijtmans, Sebastiaan G; Bouwstra, Jan B; Harmsen, Martin C; Van Luyn, Marja J A

    2010-06-01

    Microspheres (MSs) can function as multifunctional scaffolds in different approaches of tissue repair (TR), as a filler, a slow-release depot for growth factors, or a delivery vehicle for cells. Natural cell adhesion-supporting extracellular matrix components like gelatin are good materials for these purposes. Recombinant production of gelatin allows for on-demand design of gelatins, which is why we aim at developing recombinant gelatin (RG) MSs for TR. Two types of MSs (50 < Ø < 100 microm) were prepared by crosslinking two RGs, Syn-RG, and the arginine-glycine-aspartate-containing Hu-RG. The MSs were characterized, and their tissue reaction and degradation in rats was examined. Histological analysis of the explants after 14 and 28 days in vivo also showed that Syn-RG was degraded slower than Hu-RG, which correlated with the in vitro degradation assay. Hu-RG explants displayed more cellular ingrowth (60% vs. 15% for Syn-RG at day 14), which was associated with extracellular matrix deposition and vascularization. The infiltrating cells consisted of mainly macrophages, part of which fused to giant cells locally, and fibroblasts. No differences were found in matrix metalloproteinase mRNA levels, whereas gelatinase activity was clearly higher in Hu-RG explants. In conclusion, the in vitro and in vivo results of these novel formulations pave the way for cell- and/or factor-driven TR by these RG MSs. PMID:20102269

  4. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  5. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  6. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells.

    PubMed

    Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

    2014-01-01

    Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee. PMID:24592390

  7. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  8. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process.

    PubMed

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix-only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications. PMID

  9. Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila.

    PubMed

    Kashio, Soshiro; Obata, Fumiaki; Zhang, Liu; Katsuyama, Tomonori; Chihara, Takahiro; Miura, Masayuki

    2016-02-16

    Regulatory mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to induce local damage, independent of genetic manipulations in uninjured parts of the body. Herein, we develop a system in Drosophila for spatiotemporal tissue injury using a temperature-sensitive form of diphtheria toxin A domain driven by the Q system to study factors contributing to imaginal disc repair. Using this technique, we demonstrate that methionine metabolism in the fat body, a counterpart of mammalian liver and adipose tissue, supports the repair processes of wing discs. Local injury to wing discs decreases methionine and S-adenosylmethionine, whereas it increases S-adenosylhomocysteine in the fat body. Fat body-specific genetic manipulation of methionine metabolism results in defective disc repair but does not affect normal wing development. Our data indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing discs influences fat body metabolism, and proper control of methionine metabolism in the fat body, in turn, affects wing regeneration. PMID:26831070

  10. A radiation damage repair model for normal tissues

    NASA Astrophysics Data System (ADS)

    Partridge, Mike

    2008-07-01

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions (~2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 µm h-1 for large lesions (>15 000 cells).

  11. Laparoscopic Repair of Bochdalek Diaphragmatic Hernia in Adults

    PubMed Central

    Machado, Norman Oneil

    2016-01-01

    Bochdalek hernia (BH) is an uncommon form of diaphragmatic hernia. The rarity of this hernia and its nonspecific presentation leads to delay in the diagnosis, with the potential risk of complications. This review summarizes the relevant aspects of its presentation and management, based on the present evidence in the literature. A literature search was performed on PubMed, Google Scholar, and EMBASE for articles in English on BH in adults. All case reports and series from the period after 1955 till January 2015 were included. A total of 180 articles comprising 368 cases were studied. The mean age of these patients was 51 years (range 15-90 years) with a male preponderance of 57% (211/368). Significantly, 6.5% of patients were above 70 years, with 3.5% of these being above 80 years. The majority of the hernias were on the left side (63%), with right-sided hernias and bilateral occurring in 27% and 10%, respectively. Precipitating factors were noted in 24%, with 5.3% of them being pregnant. Congenital anomalies were seen in 11%. The presenting symptoms included abdominal (62%), respiratory (40%), obstructive (vomiting/abdominal distension; 36%), strangulation (26%); 14% of them were asymptomatic (detected incidentally). In the 184 patients who underwent surgical intervention, the surgical approach involved laparotomy in 74 (40.27%), thoracotomy in 50 (27.7%), combined thoracoabdominal approach in 27 (14.6%), laparoscopy in 23 (12.5%), and thoracoscopic repair in 9 (4.89%). An overall recurrence rate of 1.6% was noted. Among these patients who underwent laparoscopic repair, 82% underwent elective procedure; 66% underwent primary repair, with 61% requiring interposition of mesh or reenforcement with or without primary repair. The overall mortality was 2.7%. Therefore, BH should form one of the differential diagnoses in patients who present with simultaneous abdominal and chest symptoms. Minimal access surgery offers a good alternative with short hospital stay and is

  12. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  13. Rational design of nanofiber scaffolds for orthopedic tissue repair and regeneration

    PubMed Central

    Ma, Bing; Xie, Jingwei; Jiang, Jiang; Shuler, Franklin D; Bartlett, David E

    2013-01-01

    This article reviews recent significant advances in the design of nanofiber scaffolds for orthopedic tissue repair and regeneration. It begins with a brief introduction on the limitations of current approaches for orthopedic tissue repair and regeneration. It then illustrates that rationally designed scaffolds made up of electrospun nanofibers could be a promising solution to overcome the problems that current approaches encounter. The article also discusses the intriguing properties of electrospun nanofibers, including control of composition, structures, orders, alignments and mechanical properties, use as carriers for topical drug and/or gene sustained delivery, and serving as substrates for the regulation of cell behaviors, which could benefit musculoskeletal tissue repair and regeneration. It further highlights a few of the many recent applications of electrospun nanofiber scaffolds in repairing and regenerating various orthopedic tissues. Finally, the article concludes with perspectives on the challenges and future directions for better design, fabrication and utilization of nanofiber scaffolds for orthopedic tissue engineering. PMID:23987110

  14. Immune modulation by MANF promotes tissue repair and regenerative success in the retina.

    PubMed

    Neves, Joana; Zhu, Jie; Sousa-Victor, Pedro; Konjikusic, Mia; Riley, Rebeccah; Chew, Shereen; Qi, Yanyan; Jasper, Heinrich; Lamba, Deepak A

    2016-07-01

    Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies. PMID:27365452

  15. Magnetic resonance techniques to quantify tissue damage, tissue repair, and functional cortical reorganization in multiple sclerosis.

    PubMed

    Filippi, M; Agosta, F

    2009-01-01

    A dramatic paradigm shift is taking place in our understanding of the pathophysiology of multiple sclerosis (MS). An important contribution to such a shift has been made possible by the advances in magnetic resonance imaging (MRI) technology, which allows structural damage to be quantified in the brains of patients with MS and to be followed over the course of the disease. Modern quantitative MR techniques have reshaped the picture of MS, leading to the definition of the so- called "axonal hypothesis" (i.e., changes in axonal metabolism, morphology, or density are important determinants of functional impairment in MS). Metrics derived from magnetization transfer and diffusion-weighted MRI enable us to quantify the extent of structural changes occurring within T2-visible lesions and normal-appearing tissues (including gray matter), with increased pathological specificity over conventional MRI to irreversible tissue damage; proton MR spectroscopy adds valuable pieces of information on the biochemical nature of such changes. Finally, functional MRI can provide new insights into the role of cortical adaptive changes in limiting the clinical consequences of MS-related irreversible structural damage. Our current understanding of the pathophysiology of MS is that this is not only a disease of the white matter, characterized by focal inflammatory lesions, but also a disease involving more subtle and diffuse damage throughout the white and gray matter. The inflammatory and neurodegenerative components of the disease process are present from the earliest observable phases of the disease, but appear to be, at least partially, dissociated. In addition, recovery and repair play an important role in the genesis of the clinical manifestations of the disease, involving both structural changes and plastic reorganization of the cortex. This new picture of MS has important implications in the context of treatment options, since it suggests that agents that protect against

  16. Hematopoietic tissue repair under chronic low daily dose irradiation

    SciTech Connect

    Seed, T.M.

    1994-12-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3{minus}26.3 cGy d{sup {minus}1}). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 & 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity.

  17. Treatment Options for Adult Soft Tissue Sarcoma

    MedlinePlus

    ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ...

  18. Treatment Option Overview (Adult Soft Tissue Sarcoma)

    MedlinePlus

    ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ...

  19. Stages of Adult Soft Tissue Sarcoma

    MedlinePlus

    ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ...

  20. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode.

    PubMed

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S; Tremoli, Elena; Catapano, Alberico L; Norata, Giuseppe D; Bottazzi, Barbara; Garlanda, Cecilia; Mantovani, Alberto

    2015-06-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  1. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

    PubMed Central

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S.; Tremoli, Elena; Catapano, Alberico L.; Norata, Giuseppe D.; Bottazzi, Barbara; Garlanda, Cecilia

    2015-01-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  2. The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

    PubMed Central

    Zhang, Lijie; Hu, Jerry; Athanasiou, Kyriacos A.

    2011-01-01

    Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed. PMID:20201770

  3. Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

    PubMed Central

    Thangarajah, Tanujan; Pendegrass, Catherine J.; Shahbazi, Shirin; Lambert, Simon; Alexander, Susan; Blunn, Gordon W.

    2015-01-01

    Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon. PMID:26665095

  4. Complement activation in the context of stem cells and tissue repair

    PubMed Central

    Schraufstatter, Ingrid U; Khaldoyanidi, Sophia K; DiScipio, Richard G

    2015-01-01

    The complement pathway is best known for its role in immune surveillance and inflammation. However, its ability of opsonizing and removing not only pathogens, but also necrotic and apoptotic cells, is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation, to increased survival of various cell types in the presence of split products of complement, and to the production of trophic factors by cells activated by the anaphylatoxins C3a and C5a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3a and C5a. PMID:26435769

  5. Cutaneous tissue repair: practical implications of current knowledge. II.

    PubMed

    Reed, B R; Clark, R A

    1985-12-01

    This article reviews the scientific basis for the certain factors that delay wound repair in the clinical setting. A brief history of wound healing is given, followed by a discussion of endogenous local factors (bacterial infection, hypoxia, foreign body, and desiccation) and endogenous systemic factors (nutritional deficiencies, aging, coagulation disorders, and the Ehlers-Danlos syndromes) associated with poor wound repair. Also reviewed are the mechanisms by which exogenously administered agents (glucocorticoids, antineoplastic agents, and anticoagulants) may delay healing. Commonly used topical antimicrobials, their spectrum of activity, and evidence of effects on wound healing are examined. Finally, properties of commercially available wound coverings and wound care in the future are discussed. PMID:3908513

  6. Current options in umbilical hernia repair in adult patients

    PubMed Central

    Kulaçoğlu, Hakan

    2015-01-01

    Umbilical hernia is a rather common surgical problem. Elective repair after diagnosis is advised. Suture repairs have high recurrence rates; therefore, mesh reinforcement is recommended. Mesh can be placed through either an open or laparoscopic approach with good clinical results. Standard polypropylene mesh is suitable for the open onlay technique; however, composite meshes are required for laparoscopic repairs. Large seromas and surgical site infection are rather common complications that may result in recurrence. Obesity, ascites, and excessive weight gain following repair are obviously potential risk factors. Moreover, smoking may create a risk for recurrence. PMID:26504420

  7. Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle.

    PubMed

    Pereira, Marcelo G; Silva, Meiricris T; Carlassara, Eduardo O C; Gonçalves, Dawit A; Abrahamsohn, Paulo A; Kettelhut, Isis C; Moriscot, Anselmo S; Aoki, Marcelo S; Miyabara, Elen H

    2014-10-01

    This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases. PMID:25268835

  8. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    PubMed Central

    Pereira, Marcelo G.; Silva, Meiricris T.; Carlassara, Eduardo O. C.; Gonçalves, Dawit A.; Abrahamsohn, Paulo A.; Kettelhut, Isis C.; Moriscot, Anselmo S.; Aoki, Marcelo S.; Miyabara, Elen H.

    2014-01-01

    This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases. PMID:25268835

  9. Functional Tissue Engineering of Tendon: Establishing Biological Success Criteria for Improving Tendon Repair

    PubMed Central

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2013-01-01

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: 1) scleraxis-expressing cells; 2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and 3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. PMID:24200342

  10. Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair.

    PubMed

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2014-06-27

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. PMID:24200342

  11. The Application of Tissue Engineering Procedures to Repair the Larynx

    ERIC Educational Resources Information Center

    Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

    2006-01-01

    The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

  12. The Adult With Repaired Coarctation: Need for Lifelong Surveillance.

    PubMed

    Vonder Muhll, Isabelle F; Sehgal, Tarun; Paterson, D Ian

    2016-08-01

    Because surgical repair for coarctation of the aorta has been performed since 1945, growing numbers of patients with repaired coarctation are reaching adulthood. Primary transcatheter intervention for coarctation emerged as an alternative to surgery after 1983, and it provides comparable relief of the aortic gradient with few complications at a cost of an increased need for reintervention and a higher risk of aneurysm after repair. Although short-term outcomes are good after coarctation repair, alterations of vascular form and function persist. Mortality is increased after coarctation repair compared with that in the general population, which is related to several predictable complications. Hypertension mediates much of the late morbidity with increased rates of stroke, coronary artery disease, and heart failure after coarctation repair. Prevalence of hypertension in patients with coarctation increases over time, with a majority of patients being affected by middle age. Other late complications include recoarctation, which can usually be addressed with percutaneous balloon dilation and stenting with covered stents. Aneurysms at the coarctation repair site and the ascending aorta require surveillance with imaging and timely treatment. Intracranial aneurysms occur 5 times more commonly in patients with coarctation than in the general population. Finally, bicuspid aortic valve disease, which is present in at least half of these patients, requires surveillance and ultimately becomes the most common reason for reoperation. Awareness, identification, and appropriate treatment of long-term complications after coarctation repair are paramount to reducing long-term morbidity and mortality. PMID:27084076

  13. Macrophage activation-induced thymosin beta 4 production: a tissue repair mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macrophages play significant role in immunity which not only kill pathogens, produce cytokines but also clear dead tissues at the site of inflammation and stimulate wound healing. Much less is known how these cells contribute to tissue repair process. In course of our studies comparing the peptide...

  14. Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-02-01

    Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

  15. Composite tissue flap at perforating branches of saphenous artery: a new design for repairing composite tissue defects in anterior knee

    PubMed Central

    Sun, Guangfeng; Nie, Kaiyu; Jin, Wenhu; Wei, Zairong; Qi, Jianping; Wang, Dali

    2015-01-01

    So far it has been difficult to repair and reconstruct the composite tissue defects in knee. Saphenous artery flap has been widely used to repair complex wounds, but the design and clinical application of composite tissue flap at perforating branches of saphenous artery were not reported. In this research, we design a new composite tissue flap by carrying fascial flap in the medial gastrocnemius muscle with perforators flap in saphenous artery to repair and reconstruct the composite tissue defects in knee. By anatomic observation and analysis, we find that there exists blood-supply in netty form among saphenous arteries, medial artery below the knee, intermuscular branch in high-order position of posterior tibial artery and perforating branch in medial artery of calf. We chose saphenous artery as blood-supplying artery; utilized the netty blood-supplying mode in middle-up and medial part of shank; cut the composite tissue flap at perforating branches of saphenous artery with fascial flap carried in the medial gastrocnemius muscle; reconstructed the ligamentum patellae using medial head of gastrocnemius muscle and Achilles’s tendon; and covered the wounds at front side of knee with flap. Composite tissues were survived completely, free from infection at wounds and exosmosis of joint fluid. Motion function of knee-joint proved satisfactory, and ambulatory function was recovered. There was no complication in donor site. Composite tissue flap at perforating branches of saphenous artery with fascial flap carried in the medial gastrocnemius muscle is one of the most ideal solutions for repairing the composite tissue defects at front side of knee joint. PMID:26885090

  16. Design and characterization of a tissue-engineered bilayer scaffold for osteochondral tissue repair.

    PubMed

    Giannoni, Paolo; Lazzarini, Erica; Ceseracciu, Luca; Barone, Alberto C; Quarto, Rodolfo; Scaglione, Silvia

    2015-10-01

    Treatment of full-thickness cartilage defects relies on osteochondral bilayer grafts, which mimic the microenvironment and structure of the two affected tissues: articular cartilage and subchondral bone. However, the integrity and stability of the grafts are hampered by the presence of a weak interphase, generated by the layering processes of scaffold manufacturing. We describe here the design and development of a bilayer monolithic osteochondral graft, avoiding delamination of the two distinct layers but preserving the cues for selective generation of cartilage and bone. A highly porous polycaprolactone-based graft was obtained by combining solvent casting/particulate leaching techniques. Pore structure and interconnections were designed to favour in vivo vascularization only at the bony layer. Hydroxyapatite granules were added as bioactive signals at the site of bone regeneration. Unconfined compressive tests displayed optimal elastic properties and low residual deformation of the graft after unloading (< 3%). The structural integrity of the graft was successfully validated by tension fracture tests, revealing high resistance to delamination, since fractures were never displayed at the interface of the layers (n = 8). Ectopic implantation of grafts in nude mice, after seeding with bovine trabecular bone-derived mesenchymal stem cells and bovine articular chondrocytes, resulted in thick areas of mature bone surrounding ceramic granules within the bony layer, and a cartilaginous alcianophilic matrix in the chondral layer. Vascularization was mostly observed in the bony layer, with a statistically significant higher blood vessel density and mean area. Thus, the easily generated osteochondral scaffolds, since they are mechanically and biologically functional, are suitable for tissue-engineering applications for cartilage repair. PMID:23172816

  17. Tissue Engineering for Rotator Cuff Repair: An Evidence-Based Systematic Review

    PubMed Central

    Maffulli, Nicola; Longo, Umile Giuseppe; Loppini, Mattia; Berton, Alessandra; Spiezia, Filippo; Denaro, Vincenzo

    2012-01-01

    The purpose of this systematic review was to address the treatment of rotator cuff tears by applying tissue engineering approaches to improve tendon healing, specifically platelet rich plasma (PRP) augmentation, stem cells, and scaffolds. Our systematic search was performed using the combination of the following terms: “rotator cuff”, “shoulder”, “PRP”, “platelet rich plasma”, “stemcells”, “scaffold”, “growth factors”, and “tissue engineering”. No level I or II studies were found on the use of scaffolds and stem cells for rotator cuff repair. Three studies compared rotator cuff repair with or without PRP augmentation. All authors performed arthroscopic rotator cuff repair with different techniques of suture anchor fixation and different PRP augmentation. The three studies found no difference in clinical rating scales and functional outcomes between PRP and control groups. Only one study showed clinical statistically significant difference between the two groups at the 3-month follow up. Any statistically significant difference in the rates of tendon rerupture between the control group and the PRP group was found using the magnetic resonance imaging. The current literature on tissue engineering application for rotator cuff repair is scanty. Comparative studies included in this review suggest that PRP augmented repair of a rotator cuff does not yield improved functional and clinical outcome compared with non-augmented repair at a medium and long-term followup. PMID:25098365

  18. Repair of a postappendectomy massive ventral hernia using tissue expanders

    PubMed Central

    Celebi, Fatih; Erozgen, Fazilet; Ergun, Selma Sonmez; Akaydin, Murat; Kaplan, Rafet

    2013-01-01

    Reconstruction of large abdominal wall defects is a challenging problem. Various reconstructive techniques have been described in the surgical literature each with its advantages and disadvantages. In this report we describe our experience in treating a patient with large abdominal wall defect by staged abdominal wall reconstruction utilizing prosthetic mesh in conjunction with tissue expanders. A 41-year-old male presented with abdominal pain. Exploratory laparotomy showed perforated appendicitis with intraabdominal abscess of 1,500 mL. Postoperatively, he developed intraperitoneal sepsis. To prevent abdominal compartment syndrome, he was reoperated and left with "open abdomen". After several open abdomen lavages, his abdominal wall defect was allowed to granulate. After epithelization of the defect, the abdominal wall was reconstructed using prosthetic mesh and tissue expanders. The tissue expansion process was well tolerated. We suggest that the use of tissue expanders provides reliable and well-vascularized soft-tissue coverage in abdominal wall reconstruction. PMID:23323238

  19. Modulation of tissue repair by regeneration enhancer elements.

    PubMed

    Kang, Junsu; Hu, Jianxin; Karra, Ravi; Dickson, Amy L; Tornini, Valerie A; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A; Black, Brian L; Poss, Kenneth D

    2016-04-14

    How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs. PMID:27049946

  20. [Radiotherapy of adult soft tissue sarcoma].

    PubMed

    Le Péchoux, C; Moureau-Zabotto, L; Llacer, C; Ducassou, A; Sargos, P; Sunyach, M P; Thariat, J

    2016-09-01

    Incidence of soft tissue sarcoma is low and requires multidisciplinary treatment in specialized centers. The objective of this paper is to report the state of the art regarding indications and treatment techniques of main soft tissue sarcoma localisations. PMID:27523415

  1. Implanted scaffold-free prevascularized constructs promote tissue repair

    PubMed Central

    Czajka, Caitlin A.; Calder, Bennet W.; Yost, Michael J.; Drake, Christopher J.

    2014-01-01

    To evaluate the anastomotic potential of prevascular tissue constructs generated from scaffold-free self-assembly of human endothelial and fibroblast cells, tissue constructs were implanted into athymic mice and immune-competent rats. Analysis of xenografts placed into hind limb muscle defects showed vascular anastomotic activity by 3 days following implantation and persisting for 2 weeks. Integration of the implanted prevascular tissue constructs with the host circulatory system was evident from presence of red blood cells in the implant as early as 3 days following implantation. Additionally, analysis of 3-day xenografts in the rat model showed activation of skeletal muscle satellite cells based on Pax-7 and MyoD expression. We conclude that prevascular tissue constructs generated from scaffold-free self-assembly of human endothelial and fibroblast cells are a promising tool to provide both vascular supply and satellite cell activation toward the resolution of skeletal muscle injury. PMID:25668498

  2. Detection of BrdU-label Retaining Cells in the Lacrimal Gland: Implications for Tissue Repair

    PubMed Central

    You, Samantha; Tariq, Ayesha; Kublin, Claire L.; Zoukhri, Driss

    2011-01-01

    The purpose of the present study was to determine if the lacrimal gland contains 5-bromo-2’-deoxyuridine (BrdU)-label retaining cells and if they are involved in tissue repair. Animals were pulsed daily with BrdU injections for 7 consecutive days. After a chase period of 2, 4, or 12 weeks, the animals were sacrificed and the lacrimal glands were removed and processed for BrdU immunostaining. In another series of experiments, the lacrimal glands of 12-week chased animals were either left untreated or were injected with interleukin 1 (IL-1) to induce injury. Two and half day post-injection, the lacrimal glands were removed and processed for BrdU immunostaining. After 2 and 4 week of chase period, a substantial number of lacrimal gland cells were BrdU+ (11.98 ± 1.84 and 7.95 ± 1.83 BrdU+ cells/mm2, respectively). After 12 weeks of chase, there was a 97% decline in the number of BrdU+ cells (0.38 ± 0.06 BrdU+ cells/mm2), suggesting that these BrdU-label retaining cells may represent slow-cycling adult stem/progenitor cells. In support of this hypothesis, the number of BrdU labeled cells increased over 7-fold during repair of the lacrimal gland (control: 0.41 ± 0.09 BrdU+ cells/mm2, injured: 2.91 ± 0.62 BrdU+ cells/mm2). Furthermore, during repair, among BrdU+ cells 58.2 ± 3.6 % were acinar cells, 26.4 ± 4.1% were myoepithelial cells, 0.4 ± 0.4% were ductal cells, and 15.0 ± 3.0% were stromal cells. We conclude that the murine lacrimal gland contains BrdU-label retaining cells that are mobilized following injury to generate acinar, myoepithelial and ductal cells. PMID:22101331

  3. Detection of BrdU-label retaining cells in the lacrimal gland: implications for tissue repair.

    PubMed

    You, Samantha; Tariq, Ayesha; Kublin, Claire L; Zoukhri, Driss

    2011-12-01

    The purpose of the present study was to determine if the lacrimal gland contains 5-bromo-2'-deoxyuridine (BrdU)-label retaining cells and if they are involved in tissue repair. Animals were pulsed daily with BrdU injections for 7 consecutive days. After a chase period of 2, 4, or 12 weeks, the animals were sacrificed and the lacrimal glands were removed and processed for BrdU immunostaining. In another series of experiments, the lacrimal glands of 12-week chased animals were either left untreated or were injected with interleukin 1 (IL-1) to induce injury. Two and half days post-injection, the lacrimal glands were removed and processed for BrdU immunostaining. After 2 and 4 weeks of chase period, a substantial number of lacrimal gland cells were BrdU(+) (11.98 ± 1.84 and 7.95 ± 1.83 BrdU(+) cells/mm(2), respectively). After 12 weeks of chase, there was a 97% decline in the number of BrdU(+) cells (0.38 ± 0.06 BrdU(+) cells/mm(2)), suggesting that these BrdU-label retaining cells may represent slow-cycling adult stem/progenitor cells. In support of this hypothesis, the number of BrdU labeled cells increased over 7-fold during repair of the lacrimal gland (control: 0.41 ± 0.09 BrdU(+) cells/mm(2); injured: 2.91 ± 0.62 BrdU(+) cells/mm(2)). Furthermore, during repair, among BrdU(+) cells 58.2 ± 3.6 % were acinar cells, 26.4 ± 4.1% were myoepithelial cells, 0.4 ± 0.4% were ductal cells and 15.0 ± 3.0% were stromal cells. We conclude that the murine lacrimal gland contains BrdU-label retaining cells that are mobilized following injury to generate acinar, myoepithelial and ductal cells. PMID:22101331

  4. Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

    PubMed

    Klotz, Barbara J; Gawlitta, Debby; Rosenberg, Antoine J W P; Malda, Jos; Melchels, Ferry P W

    2016-05-01

    Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications. PMID:26867787

  5. Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

    PubMed Central

    Xu, Hui; Sandor, Maryellen; Lombardi, Jared

    2013-01-01

    Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of

  6. Functional role of periostin in development and wound repair: implications for connective tissue disease

    PubMed Central

    2008-01-01

    Integrity of the extracellular matrix (ECM) is essential for maintaining the normal structure and function of connective tissues. ECM is secreted locally by cells and organized into a complex meshwork providing physical support to cells, tissues, and organs. Initially thought to act only as a scaffold, the ECM is now known to provide a myriad of signals to cells regulating all aspects of their phenotype from morphology to differentiation. Matricellular proteins are a class of ECM related molecules defined through their ability to modulate cell–matrix interactions. Matricellular proteins are expressed at high levels during development, but typically only appear in postnatal tissue in wound repair or disease, where their levels increase substantially. Members of the CCN family, tenascin-C, osteopontin, secreted protein acidic rich in cysteine (SPARC), bone sialoprotein, thrombospondins, and galectins have all been classed as matricellular proteins. Periostin, a 90 kDa secreted homophilic cell adhesion protein, was recently added to matricellular class of proteins based on its expression pattern and function during development as well as in wound repair. Periostin is expressed in connective tissues including the periodontal ligament, tendons, skin and bone, and is also prominent in neoplastic tissues, cardiovascular disease, as well as in connective tissue wound repair. This review will focus on the functional role of periostin in tissue physiology. Fundamentally, it appears that periostin influences cell behaviour as well as collagen fibrillogenesis, and therefore exerts control over the structural and functional properties of connective tissues in both health and disease. Periostin is a novel matricellular protein with close homology to Drosophila fasciclin 1. In this review, the functional role of periostin is discussed in the context of connective tissue physiology, in development, disease, and wound repair. PMID:18642132

  7. DNA repair gene expression in biological tissues exposed to low-intensity infrared laser.

    PubMed

    de Souza da Fonseca, Adenilson; Mencalha, Andre Luiz; Araújo de Campos, Vera Maria; Ferreira Machado, Samara Cristina; de Freitas Peregrino, Antonio Augusto; Geller, Mauro; de Paoli, Flavia

    2013-07-01

    Special properties of laser light have led to its usefulness in many applications in therapy. Excitation of endogenous chromophores in biotissues and generation of free radicals could be involved in its biological effects. DNA lesions induced by free radicals are repaired by base excision repair pathway. In this work, we evaluated the expression of APE1 and OGG1 genes related to repair of DNA lesions induced by free radicals. Skin and muscle tissues of Wistar rats were exposed to low-intensity infrared laser at different fluences and frequencies. After laser exposition of 1 and 24 h, tissue samples were withdrawn for total RNA extraction, cDNA synthesis, and evaluation of APE1 and OGG1 gene expression by quantitative polymerase chain reaction. Data obtained show that laser radiation alters the expression of APE1 and OGG1 mRNA differently in skin and muscle tissues of Wistar rats depending of the fluence, frequency, and time after exposure. Our study suggests that low-intensity infrared laser affects expression of genes involved in repair of DNA lesions by base excision repair pathway. PMID:22941447

  8. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

    PubMed Central

    Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

    2014-01-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

  9. Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design

    PubMed Central

    Ogle, Molly E; Segar, Claire E; Sridhar, Sraeyes; Botchwey, Edward A

    2016-01-01

    Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their

  10. Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design.

    PubMed

    Ogle, Molly E; Segar, Claire E; Sridhar, Sraeyes; Botchwey, Edward A

    2016-05-01

    Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their

  11. Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair.

    PubMed

    Zani, Brett G; Kojima, Koji; Vacanti, Charles A; Edelman, Elazer R

    2008-05-13

    The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unclear from vascular repair studies whether endothelial implants recapitulate the vascular epithelial lining or expose injured tissues to endothelial cells (ECs) with unique healing potential because ECs line the vascular epithelium and the vasa vasorum. We examined this issue in a nonvascular tubular system, asking whether airway repair is controlled by bronchial epithelial cells (EPs) or by ECs of the perfusing bronchial vasculature. Localized bronchial denuding injury damaged epithelium, narrowed bronchial lumen, and led to mesenchymal cell hyperplasia, hypervascularity, and inflammatory cell infiltration. Peribronchial TE constructs embedded with EPs or ECs limited airway injury, although optimum repair was obtained when both cells were present in TE matrices. EC and EP expression of PGE(2), TGFbeta1, TGFbeta2, GM-CSF, IL-8, MCP-1, and soluble VCAM-1 and ICAM-1 was altered by matrix embedding, but expression was altered most significantly when both cells were present simultaneously. EPs may provide for functional control of organ injury and fibrous response, and ECs may provide for preservation of tissue perfusion and the epithelium in particular. Together the two cells optimize functional restoration and healing, suggesting that multiple cells of a tissue contribute to the differentiated biochemical function and repair of a tissue, but need not assume a fixed, ordered architectural relationship, as in intact tissues, to achieve these effects. PMID:18458330

  12. Lung tissue flap repairs esophagus defection with an inner chitosan tube stent

    PubMed Central

    Chen, Gang; Shi, Wen-Jun

    2009-01-01

    AIM: To repair the partial esophagus defect with a chitosan stent, a new esophageal prosthesis made of pulmonary tissue with vascular pedicle. METHODS: Fifteen Japanese big ear white rabbits were divided into experimental group (n = 10) and control group (n = 5). Esophagus defect in rabbits of experimental group was repaired using lung tissue flap with a chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. Esophagus defect of rabbits in control group was repaired using lung tissue flap with no chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. RESULTS: In the experimental group, 6 rabbits survived for over two weeks, the lung tissue flap healed esophageal defection, and squamous metaplasia occurred on the surface of lung tissue flap. At week 10 after operation, barium sulphate examination found that barium was fluent through the esophagus with no stricture or back stream, the creeping was good. In the control group, 4 rabbits survived for two weeks, the lung tissue flap healed esophageal defection with fibrous tissue hyperplasia, barium sulphate examination found that barium was fluent through the esophagus with a slight stricture or back stream, and the creeping was not good at week 10 after operation. CONCLUSION: Esophagus defect can be repaired using lung tissue flap with an inner chitosan tube stent. PMID:19322927

  13. Epimorphic regeneration approach to tissue replacement in adult mammals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor...

  14. Right Ventricular Mass is Associated with Exercise Capacity in Adults with Repaired Tetralogy of Fallot.

    PubMed

    O'Meagher, Shamus; Seneviratne, Martin; Skilton, Michael R; Munoz, Phillip A; Robinson, Peter J; Malitz, Nathan; Tanous, David J; Celermajer, David S; Puranik, Rajesh

    2015-08-01

    The relationship between exercise capacity and right ventricular (RV) structure and function in adult repaired tetralogy of Fallot (TOF) is poorly understood. We therefore aimed to examine the relationships between cardiac MRI and cardiopulmonary exercise test variables in adult repaired TOF patients. In particular, we sought to determine the role of RV mass in determining exercise capacity. Eighty-two adult repaired TOF patients (age at evaluation 26 ± 10 years; mean age at repair 2.5 ± 2.8 years; 23.3 ± 7.9 years since repair; 53 males) (including nine patients with tetralogy-type pulmonary atresia with ventricular septal defect) were prospectively recruited to undergo cardiac MRI and cardiopulmonary exercise testing. As expected, these repaired TOF patients had RV dilatation (indexed RV end-diastolic volume: 153 ± 43.9 mL/m(2)), moderate-severe pulmonary regurgitation (pulmonary regurgitant fraction: 33 ± 14 %) and preserved left (LV ejection fraction: 59 ± 8 %) and RV systolic function (RV ejection fraction: 51 ± 7 %). Exercise capacity was near-normal (peak work: 88 ± 17 % predicted; peak oxygen consumption: 84 ± 17 % predicted). Peak work exhibited a significant positive correlation with RV mass in univariate analysis (r = 0.45, p < 0.001) and (independent of other cardiac MRI variables) in multivariate analyses. For each 10 g higher RV mass, peak work was 8 W higher. Peak work exhibits a significant positive correlation with RV mass, independent of other cardiac MRI variables. RV mass measured on cardiac MRI may provide a novel marker of clinical progress in adult patients with repaired TOF. PMID:25795311

  15. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury.

    PubMed

    Duann, Pu; Lianos, Elias A; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  16. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    PubMed Central

    Duann, Pu; Lianos, Elias A.; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  17. Telocytes as a Source of Progenitor Cells in Regeneration and Repair Through Granulation Tissue.

    PubMed

    Díaz-Flores, Lucio; Gutiérrez, Ricardo; Pino García, Maria; González, Miriam; Díaz-Flores, Lucio; Francisco Madrid, Juan

    2016-01-01

    This review outlines the role of CD34+ stromal cells/telocytes (CD34+ SC/TCs) in repair and considers the following issues. Firstly, the conceptual aspects of repair, including regeneration and repair through granulation tissue (RTGT) as two types of repair, RTGT stages (inflammatory, proliferative, and remodeling), and tissue in repair as a substrate to assess the in vivo behavior of activated CD34+ SC/TCs. Subsequently, current knowledge of CD34+ SC/TCs, such as identification, characteristics, and functions, as well as possible stages (quiescent and activated) are taken into account. We then consider the role in regeneration of quiescent CD34+ SC/TCs (in unperturbed physiological conditions) as a nurse of stem cells (e.g., in the heart, skin, respiratory tree, gastrointestinal tract, liver, eye, and choroid plexus). Special attention is paid to the characteristics of activated CD34+ SC/TCs and the overlapping steps of activation with and without loss of CD34 expression and with and without gain of αSMA expression. With this contribution, we establish the role of CD34+ SC/TCs as progenitor cells and as a source of fibroblasts and myofibroblasts in repair through granulation tissue, fibrosis, and tumor stroma. Activated CD34+ SC/TCs in encapsulation and other processes (e.g., Reinke's edema, cutaneous myxoid cyst, mixomatous mitral valve degeneration, and fibrous papula of the face) are also outlined. Finally, similarities between modifications of CD34+ SC/TCs during in vivo activation and of multipotent mesenchymal stromal/stem cells in culture are examined in order to correlate the growing literature on CD34+ SC/TCs and the exponential research in cultured mesenchymal stromal/stem cells. PMID:26423297

  18. Theoretical versus Ex Vivo Assessment of Radiation Damage Repair: An Investigation in Normal Breast Tissue.

    PubMed

    Ebert, Martin A; Dhal, Bipina; Prunster, Janelle; McLaren, Sally; Zeps, Nikolajs; House, Michael; Reniers, Brigitte; Verhaegen, Frank; Corica, Tammy; Saunders, Christobel; Joseph, David J

    2016-04-01

    In vivo validation of models of DNA damage repair will enable their use for optimizing clinical radiotherapy. In this study, a theoretical assessment was made of DNA double-strand break (DSB) induction in normal breast tissue after intraoperative radiation therapy (IORT), which is now an accepted form of adjuvant radiotherapy for selected patients with early breast cancer. DSB rates and relative biological effectiveness (RBE) were calculated as a function of dose, radiation quality and dose rate, each varying based on the applicator size used during IORT. The spectra of primary electrons in breast tissue adjacent to each applicator were calculated using measured X-ray spectra and Monte Carlo methods, and were used to inform a Monte Carlo damage simulation code. In the absence of repair, asymptotic RBE values (relative to (60)Co) were approximately 1.5. Beam-quality changes led to only minor variations in RBE among applicators, though differences in dose rate and overall dose delivery time led to larger variations and a rapid decrease in RBE. An experimental assessment of DSB induction was performed ex vivo using pre- and postirradiation tissue samples from patients receiving breast intraoperative radiation therapy. Relative DSB rates were assessed via γ-H2AX immunohistochemistry using proportional staining. Maximum-likelihood parameter estimation yielded a DSB repair halftime of 25.9 min (95% CI, 21.5-30.4 min), although the resulting model was not statistically distinguishable from one where there was no change in DSB yield among patients. Although the model yielded an in vivo repair halftime of the order of previous estimates for in vitro repair halftimes, we cannot conclude that it is valid in this context. This study highlights some of the uncertainties inherent in population analysis of ex vivo samples, and of the quantitative limitations of immunohistochemistry for assessment of DSB repair. PMID:27023258

  19. The landscape of genomic imprinting across diverse adult human tissues.

    PubMed

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K; Rivas, Manuel A; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S; Kukurba, Kim R; Zhang, Rui; Eng, Celeste; Torgerson, Dara G; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R; Burchard, Esteban G; Seibold, Max A; MacArthur, Daniel G; Montgomery, Stephen B; Zaitlen, Noah A; Lappalainen, Tuuli

    2015-07-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  20. The landscape of genomic imprinting across diverse adult human tissues

    PubMed Central

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

    2015-01-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  1. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    PubMed

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  2. MKP-1 coordinates ordered macrophage-phenotype transitions essential for stem cell-dependent tissue repair.

    PubMed

    Perdiguero, Eusebio; Kharraz, Yacine; Serrano, Antonio L; Muñoz-Cánoves, Pura

    2012-03-01

    Re-establishing tissue homoeostasis in response to injury requires infiltration of inflammatory cells and activation of resident stem cells. However, full tissue recovery also requires that the inflammation is resolved. While it is known that disturbing the interactions between inflammatory cells and tissue resident cells prevents successful healing, the molecular mechanisms underlying the paracrine interactions between these cell types are practically unknown. Here, and in a recent study, we provide mechanistic evidence that macrophages control stem cell-dependent tissue repair. In particular, we found that the temporal spacing of the pro- to anti-inflammatory macrophage polarization switch is controlled by the balance of p38 MAPK (termed here p38) and the MAPK phosphatase MKP-1 during the muscle healing process. Moreover, we demonstrate a new function for MKP-1-regulated p38 signaling in deactivating macrophages during inflammation resolution after injury. Specifically, at advanced stages of regeneration, MKP-1 loss caused an unscheduled "exhaustion-like" state in muscle macrophages, in which neither pro- nor anti-inflammatory cytokines are expressed despite persistent tissue damage, leading to dysregulated reparation by the tissue stem cells. Mechanistically, we demonstrate that p38 and MKP-1 control the AKT pathway through a miR-21-dependent PTEN regulation. Importantly, both genetic and pharmacological interference with the individual components of this pathway restored inflammation-dependent tissue homeostasis in MKP-1-deficient mice and delayed inflammation resolution and tissue repair dysregulation in wild-type mice. Because the process of tolerance to bacterial infection involves a progressive attenuation of pro-inflammatory gene expression, we discuss here the potential similarities between the mechanisms underlying inflammation resolution during tissue repair and those controlling endotoxin tolerance. PMID:22361726

  3. Present status and applications of bacterial cellulose-based materials for skin tissue repair.

    PubMed

    Fu, Lina; Zhang, Jin; Yang, Guang

    2013-02-15

    Bacterial cellulose (BC, also known as microbial cellulose, MC) is a promising natural polymer which is biosynthesized by certain bacteria. This review focused on BC-based materials which can be utilized for skin tissue repair. Firstly, it is illustrated that BC has unique structural and mechanical properties as compared with higher plant cellulose, and is thus expected to become a commodity material. Secondly, we summarized the basic properties and different types of BC, including self-assembled, oriented BC, and multiform BC. Thirdly, composites prepared by using BC in conjunction with other polymers are explored, and the research on BC for application in skin tissue engineering is addressed. Finally, experimental results and clinical treatments assessing the performance of wound healing materials based on BC were examined. With its superior mechanical properties, as well as its excellent biocompatibility, BC was shown to have great potential for biomedical application and very high clinical value for skin tissue repair. PMID:23399174

  4. NADPH Oxidase 1 and Its Derived Reactive Oxygen Species Mediated Tissue Injury and Repair

    PubMed Central

    Fu, Xiu-Jun; Peng, Ying-Bo; Hu, Yi-Ping; Shi, You-Zhen; Yao, Min; Zhang, Xiong

    2014-01-01

    Reactive oxygen species are mostly viewed to cause oxidative damage to various cells and induce organ dysfunction after ischemia-reperfusion injury. However, they are also considered as crucial molecules for cellular signal transduction in biology. NADPH oxidase, whose only function is reactive oxygen species production, has been extensively investigated in many cell types especially phagocytes. The deficiency of NADPH oxidase extends the process of inflammation and delays tissue repair, which causes chronic granulomatous disease in patients. NADPH oxidase 1, one member of the NADPH oxidase family, is not only constitutively expressed in a variety of tissues, but also induced to increase expression in both mRNA and protein levels under many circumstances. NADPH oxidase 1 and its derived reactive oxygen species are suggested to be able to regulate inflammation reaction, cell proliferation and migration, and extracellular matrix synthesis, which contribute to the processes of tissue injury and repair. PMID:24669283

  5. Achilles tendon repair with acellular tissue graft augmentation in neglected ruptures.

    PubMed

    Lee, Daniel K

    2007-01-01

    Neglected Achilles tendon rupture injuries present surgical challenges because of the quality and quantity of tendon tissue during repair combined with the magnitude of mechanical forces placed on this tendon. The purpose of this study was to evaluate the effects of an acellular human dermal tissue matrix, GRAFTJACKET, as an augmentation material in neglected Achilles tendon repair. Nine patients with neglected Achilles tendon ruptures were evaluated and followed up for a minimum of 20 months. Primary repair was followed by augmentation with the graft and suturing circumferentially around the tendon. Patients were placed in an early, functional rehabilitation program with postoperative evaluation at 3, 6, and 12 months. Outcome scores were calculated based on the American Orthopaedic Foot and Ankle Society ankle-hindfoot scoring system. At 20 to 30 months postoperative follow-up range, there has been no incidence of re-rupture or recurrent pain. The average return-to-activity time was 15.2 +/- 1.7 weeks. The results from this retrospective clinical series suggest that using an acellular human dermal tissue matrix to augment neglected Achilles tendon rupture primary repair offers desirable return-to-activity time points and viable surgical alternative over previously reported surgical options. PMID:17980842

  6. Hypospadias repair using laser tissue soldering (LTS): preliminary results of a prospective randomized study

    NASA Astrophysics Data System (ADS)

    Kirsch, Andrew J.; Cooper, Christopher S.; Canning, Douglas A.; Snyder, Howard M., III; Zderic, Stephen A.

    1998-07-01

    Purpose: The purpose of this study was to evaluate laser tissue soldering using an 808 nm diode laser and wavelength- matched human albumin solder for urethral surgery in children. Methods: Currently, 30 boys, ages 3 months to 8 years were randomized to standard suturing (n equals 22) or 'sutureless' laser hypospadias repair (n equals 18). Laser soldering was performed with a human albumin solder doped with indocyanine green dye (2.5 mg/ml) using a laser power output of 0.5 W, pulse duration of 0.5 sec, and interval of 0.1 sec. Power density was approximately 16 W/cm2. In the laser group, sutures were used for tissue alignment only. At the time of surgery, neourethral and penile lengths, operative time for urethral repair, and number of sutures/throws were measured. Postoperatively, patients were examined for complications of wound healing, stricture, or fistula formation. Results: Mean age, severity of urethral defect, type of repair, and neourethra length were equivalent between the two groups. Operative time was significantly faster for laser soldering in both simple (1.6 plus or minus 0.21 min, p less than 0.001) and complex (5.4 plus or minus 0.28 min, p less than 0.0001) hypospadias repairs compared to controls (10.6 plus or minus 1.4 min and 27.8 plus or minus 2.9 min, respectively). The mean number of sutures used in the laser group for simple and complex repairs (3.3 plus or minus 0.3 and 8.1 plus or minus 0.64, respectively) were significantly (p less than 0.0001) less than for controls (8.2 plus or minus 0.84 and 20 plus or minus 2.3, respectively). Followup was between 3 months and 14 months. The overall complication rate in the laser group (11%) was lower than the controls (23%). However, statistical significance (p less than 0.05) was achieved only for the subgroup of patients undergoing simple repairs (LTS, 100% success versus suturing, 69% success). Conclusions: These preliminary results indicate that laser tissue soldering for hypospadias repair

  7. [The three-dimensional culture of adult mesenchymal stem cells for intervertebral disc tissue engineering].

    PubMed

    Feng, Ganjun; Liu, Hao; Deng, Li; Chen, Xiaohe; Zhao, Xianfeng; Liang, Tao; Li, Xiuqiong

    2009-12-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain. As current clinical treatments are aimed at restoring biomechanical function and providing symptomatic relief, the methods focused on biological repair have aroused interest and several tissue engineering approaches using different cell types have been proposed. Owing to the unsuitable nature of degenerate cells for tissue engineering, attention has been given to the use of mesenchymal stem cells (MSCs). In this connection, we have made a study on the characteristics of MSCs derived from adult bone marrow and on the feasibility of constructing IVD tissue-engineering cell under a Three-Dimensional Pellet Culture System. The human bone marrow MSCs were isolated and purified with density gradient solution and attachment-independent culture system. MSCs isolated using this method are a homogeneous population as indicated by morphology and other criteria. They have the capacity for self-renewal and proliferation, and the multilineage potential to differentiate. PMID:20095491

  8. Urinary bladder matrix promotes site appropriate tissue formation following right ventricle outflow tract repair

    PubMed Central

    Remlinger, Nathaniel T; Gilbert, Thomas W; Yoshida, Masahiro; Guest, Brogan N; Hashizume, Ryotaro; Weaver, Michelle L; Wagner, William R; Brown, Bryan N; Tobita, Kimimasa; Wearden, Peter D

    2013-01-01

    The current prevalence and severity of heart defects requiring functional replacement of cardiac tissue pose a serious clinical challenge. Biologic scaffolds are an attractive tissue engineering approach to cardiac repair because they avoid sensitization associated with homograft materials and theoretically possess the potential for growth in similar patterns as surrounding native tissue. Both urinary bladder matrix (UBM) and cardiac ECM (C-ECM) have been previously investigated as scaffolds for cardiac repair with modest success, but have not been compared directly. In other tissue locations, bone marrow derived cells have been shown to play a role in the remodeling process, but this has not been investigated for UBM in the cardiac location, and has never been studied for C-ECM. The objectives of the present study were to compare the effectiveness of an organ-specific C-ECM patch with a commonly used ECM scaffold for myocardial tissue repair of the right ventricle outflow tract (RVOT), and to examine the role of bone marrow derived cells in the remodeling response. A chimeric rat model in which all bone marrow cells express green fluorescent protein (GFP) was generated and used to show the ability of ECM scaffolds derived from the heart and bladder to support cardiac function and cellular growth in the RVOT. The results from this study suggest that urinary bladder matrix may provide a more appropriate substrate for myocardial repair than cardiac derived matrices, as shown by differences in the remodeling responses following implantation, as well as the presence of site appropriate cells and the formation of immature, myocardial tissue. PMID:23974174

  9. Myocardial histopathology in late-repaired and unrepaired adults with tetralogy of Fallot.

    PubMed

    Pradegan, Nicola; Vida, Vladimiro L; Geva, Tal; Stellin, Giovanni; White, Matthew T; Sanders, Stephen P; Padera, Robert F

    2016-01-01

    Survival of patients after repair of tetralogy of Fallot (TOF) is worse than for the general population. We aimed to assess the time-related effects of surgical repair on right (RV) and left ventricle (LV) myocardium by quantifying hypertrophy and fibrosis. Cardiomyocyte transverse diameter and percent of fibrosis were measured in 8 adult heart specimens with late-repaired TOF, 6 with unrepaired TOF, and 11 normal hearts (controls). The RV and LV mean and median cardiomyocyte diameter and percent of fibrosis were significantly greater than controls in both repaired and unrepaired hearts. The mean RV inferior wall myocyte diameter in unrepaired hearts was significantly greater at average age at death than in repaired hearts (24.9±2.5 vs. 16.4±1.3μm, P=.015), but not the mean RV anterior wall myocyte diameter (21.5±2.2 vs. 17±1.2μm, P=.09) or the mean LV myocyte diameter (19.7±1.5 vs. 16.7±0.8μm, P=.10). Of the RV myocyte diameter measurements, only the RV anterior wall myocyte diameter for repaired hearts correlated with age at death, while LV myocyte diameter for both repaired and unrepaired hearts correlated with age at death. None of the measures of myocyte diameter correlated with age at repair. The mean RV anterior wall, inferior wall, and LV percent fibrosis were all significantly greater in unrepaired hearts at average age at death compared with repaired hearts (16.3±1.3 vs. 13.0±0.7%, P=.04; 18.1±1.9 vs. 12.7±1.0%, P=.03; 15.7±0.8 vs. 11.6±0.4%, P=.004, respectively). There was a significant correlation between RV percent fibrosis (both locations) and age at death for repaired hearts but not for unrepaired hearts, while LV wall percent fibrosis correlated significantly with age at death for both groups. RV percent fibrosis was not significantly correlated with age at repair, while LV percent fibrosis was negatively correlated with age at repair. Hypertrophy and fibrosis in RV and LV of late-repaired TOF hearts progress during follow-up despite

  10. Cryogel-PCL combination scaffolds for bone tissue repair.

    PubMed

    Van Rie, Jonas; Declercq, Heidi; Van Hoorick, Jasper; Dierick, Manuel; Van Hoorebeke, Luc; Cornelissen, Ria; Thienpont, Hugo; Dubruel, Peter; Van Vlierberghe, Sandra

    2015-03-01

    The present work describes the development and the evaluation of cryogel-poly-ε-caprolactone combinatory scaffolds for bone tissue engineering. Gelatin was selected as cell-interactive biopolymer to enable the adhesion and the proliferation of mouse calvaria pre-osteoblasts while poly-ε-caprolactone was applied for its mechanical strength required for the envisaged application. In order to realize suitable osteoblast carriers, methacrylamide-functionalized gelatin was introduced into 3D printed poly-ε-caprolactone scaffolds created using the Bioplotter technology, followed by performing a cryogenic treatment which was concomitant with the redox-initiated, covalent crosslinking of the gelatin derivative (i.e. cryogelation). In a first part, the efficiency of the cryogelation process was determined using gel fraction experiments and by correlating the results with conventional hydrogel formation at room temperature. Next, the optimal cryogelation parameters were fed into the combinatory approach and the scaffolds developed were characterized for their structural and mechanical properties using scanning electron microscopy, micro-computed tomography and compression tests respectively. In a final part, in vitro biocompatibility assays indicated a good colonization of the pre-osteoblasts and the attachment of viable cells onto the cryogenic network. However, the results also show that the cellular infiltration throughout the entire scaffold is suboptimal, which implies that the scaffold design should be optimized by reducing the cryogel density. PMID:25690621

  11. Hanging in the balance: endogenous anti-inflammatory mechanisms in tissue repair and fibrosis.

    PubMed

    Ariel, Amiram; Timor, Orly

    2013-01-01

    Inflammation is the physiological response to tissue injury caused by pathogens or trauma. Nevertheless, inflammation should be resolved in a timely manner, resulting in elimination of the inflammatory cells and mediators from the injured tissue, to avoid its deleterious consequences. Uncontrolled inflammation can lead to inflammatory, autoimmune, and cancerous disorders that are the result of improper resolution. The healing of the injured tissue during the termination of inflammation must also be tightly controlled since excessive tissue repair can lead to fibrosis and scarring of the affected organ. In the last three decades, it has been revealed that the resolution of inflammation is tightly orchestrated by specific cells, protein, and lipid mediators that are produced at proper timing and distinct locations. The bioactivity of these anti-inflammatory, pro-resolving, and immunoregulatory agents results in clearance of the tissue from inflammatory leukocytes and their products, and the return of homeostatic tissue architecture and function. Here, we will survey the current endogenous mechanisms governing the resolution of inflammation and directing it towards injury healing and halting of acquired immune responses while preventing excessive tissue repair and fibrosis. We focus on the role played by apoptotic polymorphonuclear cells (PMNs), 15-lipoxygenase (LO)-derived lipid mediators, and TGFβ in this macrophage-governed decision-making process and suggest new modes of action for fibrosis prevention and return to homeostasis. PMID:23007838

  12. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  13. Use of Adult Stem Cells for Cartilage Tissue Engineering: Current Status and Future Developments

    PubMed Central

    Baugé, Catherine; Boumédiene, Karim

    2015-01-01

    Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. So, in recent years, researchers and surgeons have been working hard to elaborate cartilage repair interventions for patients who suffer from cartilage damage. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or hypertrophic cartilage. In the next years, the development of new strategies using adult stem cells, in scaffolds, with supplementation of culture medium and/or culture in low oxygen tension should improve the quality of neoformed cartilage. Through these solutions, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injury or chondropathies. This review discusses the current knowledge about the use of adult stem cells in the context of cartilage tissue engineering and presents clinical trials in progress, as well as in the future, especially in the field of bioprinting stem cells. PMID:26246809

  14. Biodegradable porous polyurethane scaffolds for tissue repair and regeneration.

    PubMed

    Gorna, Katarzyna; Gogolewski, Sylwester

    2006-10-01

    Critical-size bone defects usually require the insertion of autogenous bone graft to heal. Harvesting of bone is traumatic and results in high morbidity at the donor site. A potential alternative to bone graft may be a bone substitute with adequate biocompatibility and biological properties produced from ceramics or bioresorbable/biodegradable polymers. In the present study, new elastomeric biodegradable polyurethanes with an enhanced affinity toward cells and tissues were synthesized using aliphatic diisocyanate, poly(epsilon-caprolactone) diol, and biologically active 1,4:3,6-dianhydro-D-sorbitol (isosorbide diol) as chain extender. The polymers were processed into 3D porous scaffolds by applying a combined salt leaching-phase inverse process. The critical parameters controlling pore size and geometry were the solvents and nonsolvents used for scaffold preparation and the sizes of the solid porogen crystals. Scaffolds prepared from the polymer solution in solvents such as dimethylsulfoxide or methyl-2-pyrrolidone did not have a homogenous pore structure. Many pores were interconnected, but numerous pores were closed. Irrespective of the high pore-to-volume ratio (75%), the scaffolds showed poor water permeability. The best solvent for the preparation of scaffolds from the polyurethane used in the study was dimethylformamide (DMF). The type of nonsolvent admixed to the polymer solution in DMF strongly affected the scaffolds' pore structure. The elastomeric polyurethane scaffold prepared from the optimal solvent-nonsolvent mixture had regular interconnected pores, high water permeability, and a pore-to-volume ratio of 90%. The osteoconductive properties of the 3D porous polyurethane scaffolds can be additionally promoted by loading them with calcium phosphate salts such as hydroxyapatite or tricalcium phosphate, thus making them promising candidates for bone graft substitutes. PMID:16779769

  15. Surgical anatomy and utility of pedicled vascularized tissue flaps for multilayered repair of skull base defects.

    PubMed

    Safavi-Abbasi, Sam; Komune, Noritaka; Archer, Jacob B; Sun, Hai; Theodore, Nicholas; James, Jeffrey; Little, Andrew S; Nakaji, Peter; Sughrue, Michael E; Rhoton, Albert L; Spetzler, Robert F

    2016-08-01

    OBJECT The objective of this study was to describe the surgical anatomy and technical nuances of various vascularized tissue flaps. METHODS The surgical anatomy of various tissue flaps and their vascular pedicles was studied in 5 colored silicone-injected anatomical specimens. Medical records were reviewed of 11 consecutive patients who underwent repair of extensive skull base defects with a combination of various vascularized flaps. RESULTS The supraorbital, supratrochlear, superficial temporal, greater auricular, and occipital arteries contribute to the vascular supply of the pericranium. The pericranial flap can be designed based on an axial blood supply. Laterally, various flaps are supplied by the deep or superficial temporal arteries. The nasoseptal flap is a vascular pedicled flap based on the nasoseptal artery. Patients with extensive skull base defects can undergo effective repair with dual flaps or triple flaps using these pedicled vascularized flaps. CONCLUSIONS Multiple pedicled flaps are available for reconstitution of the skull base. Knowledge of the surgical anatomy of these flaps is crucial for the skull base surgeon. These vascularized tissue flaps can be used effectively as single or combination flaps. Multilayered closure of cranial base defects with vascularized tissue can be used safely and may lead to excellent repair outcomes. PMID:26613175

  16. Use of an in vitro model in tissue engineering to study wound repair and differentiation of blastema tissue from rabbit pinna.

    PubMed

    Hashemzadeh, Mohammad Reza; Mahdavi-Shahri, Nasser; Bahrami, Ahmad Reza; Kheirabadi, Masoumeh; Naseri, Fatemeh; Atighi, Mitra

    2015-08-01

    Rabbit ear wound repair is an accepted model for studies of tissue regeneration, leading to scar less wound repair. It is believed that a specific tissue, blastema, is responsible for such interesting capacity of tissue regeneration. To test this idea further and to elucidate the cellular events happening during the ear wound repair, we designed some controlled experiments in vitro. Small pieces of the ear were punched and washed immediately with normal saline. The tissues were then cultured in the Dulbecco's Modified Eagle(')s Medium, supplemented with fetal bovine serum in control group. As a treatment vitamin A and C was used to evaluate the differentiation potency of the tissue. These tissues were fixed, sectioned, stained, and microscopically studied. Micrographs of electron microscopy provided evidences revealing dedifferentiation of certain cells inside the punched tissues after incubation in tissue culture medium. The histological studies revealed that cells of the tissue (i) can undergo cellular proliferation, (ii) differentiate to epithelial, condrogenic, and osteogenic tissues, and (iii) regenerate the wounds. These results could be used for interpretation of the possible events happening during tissue engineering and wound repair in vitro. An important goal of this study is to create a tissue engineering and tissue banking model, so that in the future it could be used in further blastema tissue studies at different levels. PMID:26091624

  17. Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration.

    PubMed

    Fan, Fuqin; He, Zhixiang; Kong, Lu-Lu; Chen, Qinghua; Yuan, Quan; Zhang, Shihao; Ye, Jinjin; Liu, Hao; Sun, Xiufeng; Geng, Jing; Yuan, Lunzhi; Hong, Lixin; Xiao, Chen; Zhang, Weiji; Sun, Xihuan; Li, Yunzhan; Wang, Ping; Huang, Lihong; Wu, Xinrui; Ji, Zhiliang; Wu, Qiao; Xia, Ning-Shao; Gray, Nathanael S; Chen, Lanfen; Yun, Cai-Hong; Deng, Xianming; Zhou, Dawang

    2016-08-17

    Tissue repair and regenerative medicine address the important medical needs to replace damaged tissue with functional tissue. Most regenerative medicine strategies have focused on delivering biomaterials and cells, yet there is the untapped potential for drug-induced regeneration with good specificity and safety profiles. The Hippo pathway is a key regulator of organ size and regeneration by inhibiting cell proliferation and promoting apoptosis. Kinases MST1 and MST2 (MST1/2), the mammalian Hippo orthologs, are central components of this pathway and are, therefore, strong target candidates for pharmacologically induced tissue regeneration. We report the discovery of a reversible and selective MST1/2 inhibitor, 4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide (XMU-MP-1), using an enzyme-linked immunosorbent assay-based high-throughput biochemical assay. The cocrystal structure and the structure-activity relationship confirmed that XMU-MP-1 is on-target to MST1/2. XMU-MP-1 blocked MST1/2 kinase activities, thereby activating the downstream effector Yes-associated protein and promoting cell growth. XMU-MP-1 displayed excellent in vivo pharmacokinetics and was able to augment mouse intestinal repair, as well as liver repair and regeneration, in both acute and chronic liver injury mouse models at a dose of 1 to 3 mg/kg via intraperitoneal injection. XMU-MP-1 treatment exhibited substantially greater repopulation rate of human hepatocytes in the Fah-deficient mouse model than in the vehicle-treated control, indicating that XMU-MP-1 treatment might facilitate human liver regeneration. Thus, the pharmacological modulation of MST1/2 kinase activities provides a novel approach to potentiate tissue repair and regeneration, with XMU-MP-1 as the first lead for the development of targeted regenerative therapeutics. PMID:27535619

  18. The transcription factor Egr-1: a potential drug in wound healing and tissue repair.

    PubMed

    Braddock, M

    2001-07-01

    In the United States, between 40 and 90 million hospital days are lost per year as a result of trauma and surgical procedures which result in the loss of functional tissue. This is estimated to cost the economy and healthcare providers in excess of US$ 500 billion, a figure that is increasing because of extending population lifespan. Tissue engineering and gene therapies are radical new treatments that are aimed at tissue regeneration ranging from dermal, osteal and occular repair to the replacement of failing tissue with entire biosynthetic organs. Over the last decade, numerous proteins have been identified that are able to direct the synthesis of new tissue. Such proteins include growth factors, cytokines and, more recently, transcription factors. PMID:11491188

  19. Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine

    PubMed Central

    Arnhold, Stefan; Wenisch, Sabine

    2015-01-01

    Adipose tissue derived stem cells (ASCs) are mesenchymal stem cells which can be obtained from different adipose tissue sources within the body. It is an abundant cell pool, which is easy accessible and the cells can be obtained in large numbers, cultivated and expanded in vitro and prepared for tissue engineering approaches, especially for skeletal tissue repair. In the recent years this cell population has attracted a great amount of attention among researchers in human as well as in veterinary medicine. In the meantime ASCs have been well characterized and their use in regenerative medicine is very well established. This review focuses on the characterization of ASCs for their use for tissue engineering approaches especially in veterinary medicine and also highlights a selection of clinical trials on the basis of ASCs as the relevant cell source. PMID:25973326

  20. A New Absorbable Synthetic Substitute With Biomimetic Design for Dural Tissue Repair.

    PubMed

    Shi, Zhidong; Xu, Tao; Yuan, Yuyu; Deng, Kunxue; Liu, Man; Ke, Yiquan; Luo, Chengyi; Yuan, Tun; Ayyad, Ali

    2016-04-01

    Dural repair products are evolving from animal tissue-derived materials to synthetic materials as well as from inert to absorbable features; most of them lack functional and structural characteristics compared with the natural dura mater. In the present study, we evaluated the properties and tissue repair performance of a new dural repair product with biomimetic design. The biomimetic patch exhibits unique three-dimensional nonwoven microfiber structure with good mechanical strength and biocompatibility. The animal study showed that the biomimetic patch and commercially synthetic material group presented new subdural regeneration at 90 days, with low level inflammatory response and minimal to no adhesion formation detected at each stage. In the biological material group, no new subdural regeneration was observed and severe adhesion between the implant and the cortex occurred at each stage. In clinical case study, there was no cerebrospinal fluid leakage, and all the postoperation observations were normal. The biomimetic structure and proper rate of degradation of the new absorbable dura substitute can guide the meaningful reconstruction of the dura mater, which may provide a novel approach for dural defect repair. PMID:26526152

  1. Nuss procedure for repair of pectus excavatum after failed Ravitch procedure in adults: indications and caveats

    PubMed Central

    Kocher, Gregor J.; Gstrein, Nathalie; Jaroszewski, Dawn E.; Ewais, Mennatallah M.

    2016-01-01

    Background Recurrence of pectus excavatum (PE) is not an uncommon problem after open repair using the Ravitch technique. The optimal approach for redo surgery is still under debate, especially in adults with less chest wall pliability. Aim of this study was to investigate the usefulness and efficacy of the minimally invasive Nuss technique for repair of recurrent PE after conventional open repair. Methods We performed a retrospective multicentre review of 20 adult patients from University Hospital Bern (n=6) and the US Mayo Clinic (n=14) who underwent minimally invasive repair of recurrent PE after unsuccessful prior Ravitch procedure. Results Mean patient age at primary open correction was 21 years, with recurrence being evident after a mean duration of 10.5 years (range, 0.25–47 years). Mean age at redo surgery using the Nuss technique was 31 years, with a mean Haller index of 4.7 before and 2.5 after final correction. Main reason for redo surgery was recurrent or persistent deformity (100%), followed by chest pain (75%) and exercise intolerance (75%). No major intraoperative or postoperative complications occurred and successful correction was possible in all patients. Conclusions Although the procedure itself is more challenging, the minimally invasive Nuss technique can be safely and successfully used for repair of recurrent PE after failed open surgery. In our series final results were good to excellent in the majority of patients without major complications or recurrence.

  2. Expression of tmp21 in normal adult human tissues

    PubMed Central

    Xie, Jian; Yang, Yuan; Li, Jianbo; Hou, Jing; Xia, Kun; Song, Weihong; Liu, Shengchun

    2014-01-01

    TMP21, known as p23 protein, is one important member of the p24 protein families. The degradation of TMP21 is mediated by the ubiquitin-proteasome pathway, as with the other presenilin-associated γ-secretase complex members. NFAT plays a very important role in regulation of human TMP21 gene expression. Compared with the function of TMP21, the studies about the distribution of this protein in human tissues are limited. We collected 19 normal adult human tissues from a healthy adult man died in a traffic accident and did examination of all the tissues collected for ICH, western blot and RT-PCR. It was shown that the expression of TMP21 is at high levels in heart, liver, lung, kidney and adrenal gland; moderate levels in brain, pancreas, prostate gland, testicle, small intestine, colon, stomach, gall bladder, thyroid gland and trachea; low levels in skeletal muscle, skin and lymphonodus. TMP21 is widely existed in normal adult human tissues. The current study provided for the first time a comprehensive expression of TMP21 in normal adult human tissues. It will benefit on helping in the design and interpretation of future studies focused on expounding the function of TMP21. PMID:25356171

  3. Mesh Sacrocolpopexy Compared With Native Tissue Vaginal Repair: A Systematic Review and Meta-analysis

    PubMed Central

    SIDDIQUI, Nazema Y.; GRIMES, Cara L.; Casiano, Elizabeth R.; ABED, Husam T.; JEPPSON, Peter C.; OLIVERA, Cedric K.; SANSES, Tatiana V.; STEINBERG, Adam C.; SOUTH, Mary M.; BALK, Ethan M.; SUNG, Vivian W.

    2015-01-01

    Objective To systematically review outcomes after mesh sacrocolpopexy compared with native tissue vaginal repairs in women with apical prolapse. Data Sources We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through June 4, 2012. Methods of Study Selection For anatomic and functional analyses, we included studies comparing mesh sacrocolpopexy compared with native tissue vaginal repairs with at least 6 months follow-up. The primary outcome was anatomic “success” after surgery. Secondary outcomes were reoperation and symptom outcomes. We included large case series and comparative studies with shorter follow-up to increase power for adverse event analyses. Tabulation, Integration, and Results Evidence quality was assessed with the Grades for Recommendation, Assessment, Development and Evaluation system. Meta-analyses were performed when at least three studies reported the same outcome. We included 13 comparative studies for anatomic success, reoperation, and symptom outcomes. Moderate-quality evidence supports improved anatomic outcomes after mesh sacrocolpopexy; very low–quality evidence shows no differences in reoperation between sacrocolpopexy and native tissue vaginal repairs. Evidence was insufficient regarding which procedures result in improved bladder or bowel symptoms. Low-quality evidence showed no differences in postoperative sexual function. Adverse event data were compiled and meta-analyzed from 79 studies. When including larger noncomparative studies, ileus or small bowel obstruction (2.7% vs. 0.2%, p < 0.01), mesh or suture complications (4.2% vs. 0.4%, p < 0.01), and thromboembolic phenomena (0.6% vs. 0.1%, p = 0.03) were more common after mesh sacrocolpopexy compared to native tissue vaginal repairs. Conclusion When anatomic durability is a priority, we suggest that mesh sacrocolpopexy may be the preferred surgical option. When minimizing adverse events or reoperation is the priority, there

  4. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  5. A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue

    PubMed Central

    Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

    2015-01-01

    Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715

  6. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.

    PubMed

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  7. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

    PubMed Central

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P.; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  8. Current advances in tissue repair and regeneration: the future is bright.

    PubMed

    Ninov, Nikolay; Yun, Maximina H

    2015-04-01

    The fifth EMBO conference on 'The Molecular and Cellular Basis of Regeneration and Repair' took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re-stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans. PMID:27499870

  9. Reserve stem cells: Reprogramming of differentiated cells fuels repair, metaplasia, and neoplasia in the adult gastrointestinal tract

    PubMed Central

    Mills, Jason C.; Sansom, Owen J.

    2016-01-01

    It has long been known that differentiated cells can switch fates, especially in vitro, but only recently has there been a critical mass of publications describing the mechanisms adult, post-mitotic cells use in vivo to reverse their differentiation state. We propose that this sort of cellular reprogramming is a fundamental cellular process akin to apoptosis or mitosis. Because reprogramming can invoke regenerative cells from mature cells, it is critical to the longterm maintenance of tissues like the pancreas, which encounter large insults during adulthood but lack constitutively active adult stem cells to repair the damage. However, even in tissues with adult stem cells, like stomach and intestine, reprogramming may allow mature cells to serve as reserve (“quiescent”) stem cells when normal stem cells are compromised. We propose that the potential downside to reprogramming is that it increases risk for cancers that occur late in adulthood. Mature, long-lived cells may have years of exposure to mutagens. Mutations that affect the physiological function of differentiated, post-mitotic cells may lead to apoptosis, but mutations in genes that govern proliferation might not be selected against. Hence, reprogramming with reentry into the cell cycle might unmask those mutations, causing an irreversible progenitor-like, proliferative state. We review recent evidence showing that reprogramming fuels irreversible metaplastic and precancerous proliferations in stomach and pancreas. Finally, we illustrate how we think reprogrammed differentiated cells are likely candidates as cells of origin for cancers of the intestine. PMID:26175494

  10. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    NASA Astrophysics Data System (ADS)

    Wei, Y. T.; Tian, W. M.; Yu, X.; Cui, F. Z.; Hou, S. P.; Xu, Q. Y.; Lee, In-Seop

    2007-09-01

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  11. Drug delivery technologies and stem cells for tissue repair and regeneration.

    PubMed

    Orive, Gorka; Cobos, Raquel; Gorriti, Janire; Pedraz, Jose L; Meregalli, Mirella; Torrente, Yvan

    2015-01-01

    In the last few years several technologies are being developed for eventually repairing or replacing damaged or injured tissues and even organs. Some of these emerging technologies include the design and development of new biomaterials, the optimization of nano- and micro-technologies for drug and cell delivery, the use of autologous proteins or the application of stem cells as therapeutics. Thus, several types of stem cells, e.g. ESCs, iPSCs, MSCs, CD133+ stem cells are being evaluated for tissue regeneration purposes. The present review describes some of these emerging technologies and discusses their potential benefits and challenges. PMID:25934974

  12. Drug delivery strategies to control macrophages for tissue repair and regeneration.

    PubMed

    Garash, Reham; Bajpai, Anamika; Marcinkiewicz, Brandon M; Spiller, Kara L

    2016-05-01

    Tissue repair and regeneration is a complex process. Our bodies have an excellent capacity to regenerate damaged tissues in many situations. However, tissue healing is impaired in injuries that exceed a critical size or are exacerbated by chronic inflammatory diseases like diabetes. In these instances, biomaterials and drug delivery strategies are often required to facilitate tissue regeneration by providing physical and biochemical cues. Inflammation is the body's response to injury. It is critical for wound healing and biomaterial integration and vascularization, as long as the timing is well controlled. For example, chronic inflammation is well known to impair healing in chronic wounds. In this review, we highlight the importance of a well-controlled inflammatory response, primarily mediated by macrophages in tissue repair and regeneration and discuss various strategies designed to promote regeneration by controlling macrophage behavior. These strategies include temporally controlled delivery of anti-inflammatory drugs, delivery of macrophages as cellular therapy, controlled release of cytokines that modulate macrophage phenotype, and the design of nanoparticles that exploit the inherent phagocytic behavior of macrophages. A clear outcome of this review is that a deeper understanding of the role and timing of complex macrophage phenotypes or activation states is required to fully harness their abilities with drug delivery strategies. PMID:27190256

  13. In situ strategy for bone repair by facilitated endogenous tissue engineering.

    PubMed

    Chen, Jingdi; Zhang, Yujue; Pan, Panpan; Fan, Tiantang; Chen, Mingmao; Zhang, Qiqing

    2015-11-01

    Traditional tissue engineering procedures are expensive and time consuming. Facilitated endogenous tissue engineering (FETE) provides a solution that can avoid the ex vivo culture of autologous cells and initiate in situ reparative endogenous repair processes in vivo. This method involves fabricating a porous scaffold that mimics the environment present during the bone formation process, consisting of components that provide biomimetic interfacial interactions to cells. After the scaffold is implanted, progenitor cells provided by autologous bone marrow and surrounding tissues then differentiate to bone cells under the direction of the in situ scaffold. This paper reports a biomimetic method to prepare a hierarchically structured hybrid scaffold. Bone-like nano hydroxyapatite (HA) was crystallized from a collagen and chitosan (CC) matrix to form a porous scaffold. The in vivo study demonstrates that this nanohybrid scaffold supports excellent bone repair. This means that the FETE approach, in which the cell culture portion of traditional tissue engineering takes place in vivo, can promote the intrinsic regenerative potential of endogenous tissues. PMID:26320569

  14. 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.

  15. Alkaline diets favor lean tissue mass in older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining muscle mass in aging is important to prevent falls and fractures. The net acid load from diets that are rich in acidogenic protein and cereal grains relative to their content of alkalinogenic fruits and vegetables may contribute to reduced lean tissue mass in older adults. This analysis ...

  16. Elastin-like protein matrix reinforced with collagen microfibers for soft tissue repair.

    PubMed

    Caves, Jeffrey M; Cui, Wanxing; Wen, Jing; Kumar, Vivek A; Haller, Carolyn A; Chaikof, Elliot L

    2011-08-01

    Artificial composites designed to mimic the structure and properties of native extracellular matrix may lead to acellular materials for soft tissue repair and replacement, which display mechanical strength, stiffness, and resilience resembling native tissue. We describe the fabrication of thin lamellae consisting of continuous collagen microfiber embedded at controlled orientations and densities in a recombinant elastin-like protein polymer matrix. Multilamellar stacking affords flexible, protein-based composite sheets whose properties are dependent upon both the elastomeric matrix and collagen content and organization. Sheets are produced with properties that range over 13-fold in elongation to break (23-314%), six-fold in Young's modulus (5.3-33.1 MPa), and more than two-fold in tensile strength (1.85-4.08 MPa), exceeding that of a number of native human tissues, including urinary bladder, pulmonary artery, and aorta. A sheet approximating the mechanical response of human abdominal wall fascia is investigated as a fascial substitute for ventral hernia repair. Protein-based composite patches prevent hernia recurrence in Wistar rats over an 8-week period with new tissue formation and sustained structural integrity. PMID:21550111

  17. Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair

    PubMed Central

    Yodmuang, Supansa; McNamara, Stephanie L.; Nover, Adam B.; Mandal, Biman B.; Agarwal, Monica; Kelly, Terri-Ann N.; Chao, Pen-hsiu Grace; Hung, Clark; Kaplan, David L.; Vunjak-Novakovic, Gordana

    2014-01-01

    Cartilage tissue lacks an intrinsic capacity for self-regeneration due to slow matrix turnover, a limited supply of mature chondrocytes and insufficient vasculature. Although cartilage tissue engineering has achieved some success using agarose as a scaffolding material, major challenges of agarose-based cartilage repair, including non-degradability, poor tissue–scaffold integration and limited processing capability, have prompted the search for an alternative biomaterial. In this study, silk fiber–hydrogel composites (SF–silk hydrogels) made from silk microfibers and silk hydrogels were investigated for their potential use as a support material for engineered cartilage. We demonstrated the use of 100% silk-based fiber–hydrogel composite scaffolds for the development of cartilage constructs with properties comparable to those made with agarose. Cartilage constructs with an equilibrium modulus in the native tissue range were fabricated by mimicking the collagen fiber and proteoglycan composite architecture of native cartilage using biocompatible, biodegradable silk fibroin from Bombyx mori. Excellent chondrocyte response was observed on SF–silk hydrogels, and fiber reinforcement resulted in the development of more mechanically robust constructs after 42 days in culture compared to silk hydrogels alone. Thus, we demonstrate the versatility of silk fibroin as a composite scaffolding material for use in cartilage tissue repair to create functional cartilage constructs that overcome the limitations of agarose biomaterials, and provide a much-needed alternative to the agarose standard. PMID:25281788

  18. Elastin-like protein matrix reinforced with collagen microfibers for soft tissue repair

    PubMed Central

    Caves, Jeffrey M.; Cui, Wanxing; Wen, Jing; Kumar, Vivek A.; Haller, Carolyn A.; Chaikof, Elliot L.

    2011-01-01

    Artificial composites designed to mimic the structure and properties of native extracellular matrix may lead to acellular materials for soft tissue repair and replacement, which display mechanical strength, stiffness, and resilience resembling native tissue. We describe the fabrication of thin lamellae consisting of continuous collagen microfiber embedded at controlled orientations and densities in a recombinant elastin-like protein polymer matrix. Multilamellar stacking affords flexible, protein-based composite sheets whose properties are dependent upon both the elastomeric matrix and collagen content and organization. Sheets are produced with properties that range over 13-fold in elongation to break (23 – 314%), six-fold in Young’s modulus (5.3 to 33.1 MPa), and more than two-fold in tensile strength (1.85 to 4.08 MPa), exceeding that of a number of native human tissues, including urinary bladder, pulmonary artery, and aorta. A sheet approximating the mechanical response of human abdominal wall fascia is investigated as a fascial substitute for ventral hernia repair. Protein-based composite patches prevent hernia recurrence in Wistar rats over an 8-week period with new tissue formation and sustained structural integrity. PMID:21550111

  19. Current Concepts of Bone Tissue Engineering for Craniofacial Bone Defect Repair

    PubMed Central

    Fishero, Brian Alan; Kohli, Nikita; Das, Anusuya; Christophel, John Jared; Cui, Quanjun

    2014-01-01

    Craniofacial fractures and bony defects are common causes of morbidity and contribute to increasing health care costs. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. Current methods of repair and reconstruction include rigid fixation, grafting, and free tissue transfer. However, these methods carry innate complications, including plate extrusion, nonunion, graft/flap failure, and donor site morbidity. Recent research efforts have focused on using stem cells and synthetic scaffolds to heal critical-sized bone defects similar to those sustained from traumatic injury or ablative oncologic surgery. Growth factors can be used to augment both osteogenesis and neovascularization across these defects. Many different growth factor delivery techniques and scaffold compositions have been explored yet none have emerged as the universally accepted standard. In this review, we will discuss the recent literature regarding the use of stem cells, growth factors, and synthetic scaffolds as alternative methods of craniofacial fracture repair. PMID:25709750

  20. Investigation on laser-assisted tissue repair with NIR millisecond-long light pulses and Indocyanine Green-biopolymeric patches

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Banchelli, Martina; Cottat, Maximilien; Osticioli, Iacopo; de Angelis, Marella; Rossi, Francesca; Pini, Roberto

    2016-03-01

    In previous works a minimally invasive laser-assisted technique for vascular repair was presented. The technique rests on the photothermal adhesion of a biocompatible and bioresorbable patch containing Indocyanine Green that is brought into contact with the site to be repaired. Afterward the use of NIR millisecond-long light pulses generates a strong welding effect between the patch and the underlying tissue and in turn the repair of the wound. This technique was shown to be effective in animal model and provides several advantages over conventional suturing methods. Here we investigate and discuss the optical stability of the ICG-biopolymeric patches and the photothermal effects induced to the irradiated tissue.

  1. Emerging functions of amphiregulin in orchestrating immunity, inflammation and tissue repair

    PubMed Central

    Zaiss, Dietmar M.W.; Gause, William C.; Osborne, Lisa C.; Artis, David

    2016-01-01

    Type 2 inflammatory responses can be elicited by diverse stimuli, including toxins, venoms, allergens and infectious agents and play critical roles in resistance and tolerance associated with infection, wound healing, tissue repair and tumor development. Emerging data suggest that in addition to characteristic type 2-associated cytokines, the Epidermal Growth Factor (EGF)-like molecule Amphiregulin (AREG) may be a critical component of type 2-mediated resistance and tolerance. Notably, numerous studies demonstrate that in addition to the established role of epithelial- and mesenchymal-derived AREG, multiple leukocyte populations including mast cells, basophils, group 2 innate lymphoid cells (ILC2) and a subset of tissue-resident regulatory CD4+ T cells can express AREG. In this review, we discuss recent advances in our understanding of the AREG-EGF receptor pathway and its involvement in infection and inflammation, and propose a model for the function of this pathway in the context of resistance and tissue tolerance. PMID:25692699

  2. Failed hypospadias repair: An algorithm for secondary reconstruction using remaining local tissue.

    PubMed

    Nozohoor Ekmark, Ann; Svensson, Henry; Arnbjörnsson, Einar; Hansson, Emma

    2015-11-01

    Salvage hypospadias surgery is performed after failed primary reconstruction. Several treatment strategies have been suggested, all with pros and cons. The aim of this study was to evaluate our treatment algorithm for primary hypospadias repair applied to secondary cases in which a salvage procedure is indicated and, most importantly, local tissue is present. The algorithm was applied to 36 consecutive patients who had undergone a total of 109 surgical procedures before referral. In accordance with the algorithm, 12 patients without ventral curvature achieved a satisfactory result with one procedure by the use of local skin flaps. Six patients with moderate ventral curvature underwent orthoplasty, fistula closure, and/or urethral reconstruction using local skin flaps in one session. Eighteen patients with a severe ventral curvature or a proximal meatus were reconstructed in two stages using Byars' technique. After a median of two salvage procedures (range: 1-4), all patients but one, who awaits splitting of a skin bridge in the meatus, were successfully reconstructed. Two patients in active follow-up have potential problems requiring further surgery. Our findings indicate that failed hypospadias repairs are often due to an underestimation of the ventral curvature at the initial repair. Therefore, reevaluation of the degree of curvature is important. One-stage salvage repairs can be used, provided that none or minimal curvature remains. In cases of marked curvature, however, a meticulous resection of the chordee and ventral scarring is crucial. The subsequent repair of the large ventral defect and the long urethral reconstruction can, in most cases, be safely managed in a two-stage procedure. PMID:26195272

  3. A novel tissue-engineered bone in repairing femoral head defect and necrosis

    PubMed Central

    Peng, Wuxun; Wang, Lei; Zhang, Jian; Deng, Jin; Gong, Yuekun; Li, Shihe; Hu, Yunyu

    2015-01-01

    Objective: To evaluate the therapeutic effects of AACB/BMP/bFGF, a novel tissue-engineered bone, in repairing femoral head defect and necrosis in dog models. Methods: Dog models of avascular necrosis of femoral head (ANFH) were established by liquid nitrogen freezing method. Group A was untreated; Groups B, C, and D were implanted with AACB, AACB/BMP, and AACB/BMP/bFGF complex, respectively; Group E was grafted with autologous cancellous bone. Samples were collected at 3 w, 6 w, and 12 w after operation. A series of examinations were carried out to investigate the effects of the materials in repairing femoral head defect, including anatomical observation, X-ray examination, histological analysis, and vascular immunohistochemical staining. Results: Our results indicated that, compared with AACB alone and AACB/BMP, AACB/BMP/bFGF complex could exert the most efficient therapeutic effects in dog ANFH models. X-ray examination further confirmed that AACB/BMP/bFGF complex could effectively repair the injuries in dog ANFH models, almost to a comparable level with cancellous bone autografts. Moreover, histological analysis indicated that AACB/BMP/bFGF complex greatly enhanced the new bone formation, which would contribute to the healing of ANFH. Furthermore, vascular immunohistochemical staining revealed that AACB/BMP/bFGF complex could significantly stimulate the revascularization in defect areas, reflecting the post-injury healing process in these models. Conclusion: AACB/BMP/bFGF complex has great potential in repairing femoral head defect by enhancing osteogenesis and revascularization. The novel tissue-engineered bone would be widely used in clinical applications for ANFH treatment, especially as an alternative for autografts. PMID:25785097

  4. Type I collagen degradation during tissue repair: comparison of mechanisms following fracture and acute coronary syndromes.

    PubMed

    Stansfield, Rachel; Gossiel, Fatma; Morton, Allison; Newman, Christopher; Eastell, Richard

    2014-12-01

    There is turnover of type I collagen during tissue repair. The degradation of type I collagen by matrix metalloproteinases (MMPs) is reflected by serum ICTP and that by cathepsins by CTX-I. There is evidence for increases in ICTP after acute coronary syndromes (ACS) and in CTX-I during fracture repair. The involvement of the MMP pathway in fracture repair and cathepsins after myocardial infarction is unclear. We studied 74 men; 22 were admitted to the hospital on the day of their ACS (ST or non-ST elevation myocardial infarction) (mean age 56 years, range 39 to 82) and 9 attended hospital on the day of their tibial shaft fracture (mean age 33 years, range 21 to 79); we had 43 age-matched controls (mean age 54 years, range 20 to 82). Subjects with ACS and tibial shaft fracture were followed up for up to one year; control subjects were used to establish a reference interval. We measured serum ICTP by ELISA (reference interval 1.1 to 17.6 ng/mL) and CTX-I by chemiluminescence (reference interval 0.094 to 0.991 ng/mL). After ACS, the mean ICTP increased from 5.41 to 6.60 ng/mL within one day of admission (p<0.05); the mean CTX-I increased from 0.263 to 0.414 ng/mL (p<0.05). In two cases, the CTX increased to above the reference interval. After tibial shaft fracture, the mean ICTP increased from 5.51 to maximum of 8.71 ng/mL within 28 days of admission (p<0.01); the mean CTX increased from 0.200 to 0.374 ng/mL (p<0.001). In four cases, the CTX increased to above the reference interval. We conclude that the MMP and cathepsin pathways are both implicated in tissue repair in the bone and heart. This may have clinical implications; drugs that block either pathway (TIMPs, cathepsin K inhibitors) may affect the repair of both tissues. PMID:25193029

  5. Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation

    PubMed Central

    Cott, Catherine; Thuenauer, Roland; Landi, Alessia; Kühn, Katja; Juillot, Samuel; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Römer, Winfried

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell–cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery. PMID:26862060

  6. Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation.

    PubMed

    Cott, Catherine; Thuenauer, Roland; Landi, Alessia; Kühn, Katja; Juillot, Samuel; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Römer, Winfried

    2016-06-01

    Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell-cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery. PMID:26862060

  7. Current advances in tissue repair and regeneration: the future is bright

    PubMed Central

    2015-01-01

    Abstract The fifth EMBO conference on ‘The Molecular and Cellular Basis of Regeneration and Repair’ took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re‐stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans.

  8. Stages of the Inflammatory Response in Pathology and Tissue Repair after Intracerebral Hemorrhage.

    PubMed

    Askenase, Michael H; Sansing, Lauren H

    2016-06-01

    Intracerebral hemorrhage (ICH) is a major health concern, with high rates of mortality and morbidity and no highly effective clinical interventions. Basic research in animal models of ICH has provided insight into its complex pathology, in particular revealing the role of inflammation in driving neuronal death and neurologic deficits after hemorrhage. The response to ICH occurs in four distinct phases: (1) initial tissue damage and local activation of inflammatory factors, (2) inflammation-driven breakdown of the blood-brain barrier, (3) recruitment of circulating inflammatory cells and subsequent secondary immunopathology, and (4) engagement of tissue repair responses that promote tissue repair and restoration of neurologic function. The development of CNS inflammation occurs over many days after initial hemorrhage and thus may represent an ideal target for treatment of the disease, but further research is required to identify the mechanisms that promote engagement of inflammatory versus anti-inflammatory pathways. In this review, the authors examine how experimental models of ICH have uncovered critical mediators of pathology in each of the four stages of the inflammatory response, and focus on the role of the immune system in these processes. PMID:27214704

  9. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

    PubMed

    Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

    2016-08-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

  10. Fabrication and Application of Rose Bengal-chitosan Films in Laser Tissue Repair

    PubMed Central

    Lauto, Antonio; Stoodley, Marcus; Barton, Matthew; Morley, John W.; Mahns, David A.; Longo, Leonardo; Mawad, Damia

    2012-01-01

    Photochemical tissue bonding (PTB) is a sutureless technique for tissue repair, which is achieved by applying a solution of rose bengal (RB) between two tissue edges1,2. These are then irradiated by a laser that is selectively absorbed by the RB. The resulting photochemical reactions supposedly crosslink the collagen fibers in the tissue with minimal heat production3. In this report, RB has been incorporated in thin chitosan films to fabricate a novel tissue adhesive that is laser-activated. Adhesive films, based on chitosan and containing ~0.1 wt% RB, are fabricated and bonded to calf intestine and rat tibial nerves by a solid state laser (λ=532 nm, Fluence~110 J/cm2, spot size~0.5 cm). A single-column tensiometer, interfaced with a personal computer, is used to test the bonding strength. The RB-chitosan adhesive bonds firmly to the intestine with a strength of 15 ± 6 kPa, (n=30). The adhesion strength drops to 2 ± 2 kPa (n=30) when the laser is not applied to the adhesive. The anastomosis of tibial nerves can be also completed without the use of sutures. A novel chitosan adhesive has been fabricated that bonds photochemically to tissue and does not require sutures. PMID:23117629

  11. Linking the Primary Cilium to Cell Migration in Tissue Repair and Brain Development

    PubMed Central

    Veland, Iben Rønn; Lindbæk, Louise; Christensen, Søren Tvorup

    2014-01-01

    Primary cilia are unique sensory organelles that coordinate cellular signaling networks in vertebrates. Inevitably, defects in the formation or function of primary cilia lead to imbalanced regulation of cellular processes that causes multisystemic disorders and diseases, commonly known as ciliopathies. Mounting evidence has demonstrated that primary cilia coordinate multiple activities that are required for cell migration, which, when they are aberrantly regulated, lead to defects in organogenesis and tissue repair, as well as metastasis of tumors. Here, we present an overview on how primary cilia may contribute to the regulation of the cellular signaling pathways that control cyclic processes in directional cell migration. PMID:26955067

  12. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair

    PubMed Central

    Xin, Mei; Olson, Eric N.; Bassel-Duby, Rhonda

    2013-01-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through ‘reawakening’ pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure. PMID:23839576

  13. A method to screen and evaluate tissue adhesives for joint repair applications

    PubMed Central

    2012-01-01

    Background Tissue adhesives are useful means for various medical procedures. Since varying requirements cause that a single adhesive cannot meet all needs, bond strength testing remains one of the key applications used to screen for new products and study the influence of experimental variables. This study was conducted to develop an easy to use method to screen and evaluate tissue adhesives for tissue engineering applications. Method Tissue grips were designed to facilitate the reproducible production of substrate tissue and adhesive strength measurements in universal testing machines. Porcine femoral condyles were used to generate osteochondral test tissue cylinders (substrates) of different shapes. Viability of substrates was tested using PI/FDA staining. Self-bonding properties were determined to examine reusability of substrates (n = 3). Serial measurements (n = 5) in different operation modes (OM) were performed to analyze the bonding strength of tissue adhesives in bone (OM-1) and cartilage tissue either in isolation (OM-2) or under specific requirements in joint repair such as filling cartilage defects with clinical applied fibrin/PLGA-cell-transplants (OM-3) or tissues (OM-4). The efficiency of the method was determined on the basis of adhesive properties of fibrin glue for different assembly times (30 s, 60 s). Seven randomly generated collagen formulations were analyzed to examine the potential of method to identify new tissue adhesives. Results Viability analysis of test tissue cylinders revealed vital cells (>80%) in cartilage components even 48 h post preparation. Reuse (n = 10) of test substrate did not significantly change adhesive characteristics. Adhesive strength of fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3: 32.7 kPa, OM-4: 30.1 kPa) and was increasing with assembly time on average (2.4-fold). The screening of the different collagen formulations revealed a substance with significant higher adhesive

  14. A light-reflecting balloon catheter for atraumatic tissue defect repair.

    PubMed

    Roche, Ellen T; Fabozzo, Assunta; Lee, Yuhan; Polygerinos, Panagiotis; Friehs, Ingeborg; Schuster, Lucia; Whyte, William; Casar Berazaluce, Alejandra Maria; Bueno, Alejandra; Lang, Nora; Pereira, Maria J N; Feins, Eric; Wasserman, Steven; O'Cearbhaill, Eoin D; Vasilyev, Nikolay V; Mooney, David J; Karp, Jeffrey M; Del Nido, Pedro J; Walsh, Conor J

    2015-09-23

    A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinical translation. We developed a multifunctional, catheter-based technology with no implantable rigid components that functions by unfolding an adhesive-loaded elastic patch and deploying a double-balloon design to stabilize and apply pressure to the patch against the tissue defect site. The device uses a fiber-optic system and reflective metallic coating to uniformly disperse ultraviolet light for adhesive activation. Using this device, we demonstrate closure on the distal side of a defect in porcine abdominal wall, stomach, and heart tissue ex vivo. The catheter was further evaluated as a potential tool for tissue closure in vivo in rat heart and abdomen and as a perventricular tool for closure of a challenging cardiac septal defect in a large animal (porcine) model. Patches attached to the heart and abdominal wall with the device showed similar inflammatory response as sutures, with 100% small animal survival, indicating safety. In the large animal model, a ventricular septal defect in a beating heart was reduced to <1.6 mm. This new therapeutic platform has utility in a range of clinical scenarios that warrant minimally invasive and atraumatic repair of hard-to-reach defects. PMID:26400910

  15. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair.

    PubMed

    Zhang, Zhen-Qiang; Song, Jun-Ying; Jia, Ya-Quan; Zhang, Yun-Ke

    2016-03-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury. PMID:27127482

  16. Capturing Tissue Repair in Zebrafish Larvae with Time-lapse Brightfield Stereomicroscopy

    PubMed Central

    Lisse, Thomas S.; Brochu, Elizabeth A.; Rieger, Sandra

    2015-01-01

    The zebrafish larval tail fin is ideal for studying tissue regeneration due to the simple architecture of the larval fin-fold, which comprises of two layers of skin that enclose undifferentiated mesenchyme, and because the larval tail fin regenerates rapidly within 2-3 days. Using this system, we demonstrate a method for capturing the repair dynamics of the amputated tail fin with time-lapse video brightfield stereomicroscopy. We demonstrate that fin amputation triggers a contraction of the amputation wound and extrusion of cells around the wound margin, leading to their subsequent clearance. Fin regeneration proceeds from proximal to distal direction after a short delay. In addition, developmental growth of the larva can be observed during all stages. The presented method provides an opportunity for observing and analyzing whole tissue-scale behaviors such as fin development and growth in a simple microscope setting, which is easily adaptable to any stereomicroscope with time-lapse capabilities. PMID:25742070

  17. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair

    PubMed Central

    Zhang, Zhen-qiang; Song, Jun-ying; Jia, Ya-quan; Zhang, Yun-ke

    2016-01-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury. PMID:27127482

  18. Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration.

    PubMed

    Scotti, Celeste; Gobbi, Alberto; Karnatzikos, Georgios; Martin, Ivan; Shimomura, Kazunori; Lane, John G; Peretti, Giuseppe Michele; Nakamura, Norimasa

    2016-04-01

    Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI. PMID:26467024

  19. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes*

    PubMed Central

    ZHAO, Ming; CHEN, Zhu; LIU, Kang; WAN, Yu-qing; LI, Xu-dong; Luo, Xu-wei; Bai, Yi-guang; Yang, Ze-long; Feng, Gang

    2015-01-01

    Objective: In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods: Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society (ICRS) standard. Results: The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P<0.05). Conclusions: Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage. PMID:26537209

  20. Traumatic dislocation of the incudostapedial joint repaired with fibrin tissue adhesive.

    PubMed

    Nikolaidis, Vasilios

    2011-03-01

    We present a case of traumatic dislocation of the incudostapedial joint (ISJ) and a simple method for controlled application of the glue using commercial fibrin tissue adhesive. A 26-year-old female presented to our ENT clinic for hearing impairment to her left ear 2 months after a head trauma due to a motorcycle accident. The audiogram revealed a 40- to 50-dB HL conductive hearing loss with a notch configuration in bone conduction curve on the left ear. Computed tomography of the left temporal bone revealed a longitudinal fracture line. An exploratory tympanotomy was performed under general anesthesia. The ISJ was found dislocated while the incus was trapped by the edges of the bony lateral attic wall fracture. A small bony edge that impeded incus movement was removed and a small amount of the glue was precisely applied to the lenticular process of the incus with an angled incision knife. The long process of the incus was firmly pressed over the stapes for 30 seconds with a 90° hook and 60 seconds after the application of the glue the ISJ was repaired. One year after our patient achieved full airbone gap (ABG) closure (ABG, ≤10 dB HL), while she demonstrated overclosure in frequencies 2 and 4 kHz. Fibrin tissue glue allowed safe, rapid, and accurate repair of the ISJ and resulted in an anatomically normal articulation as the mass and shape of the ossicles was preserved. Moreover, our patient achieved full ABG closure. PMID:21344438

  1. Repair of lacerated anterior tibial tendon with acellular tissue graft augmentation.

    PubMed

    DiDomenico, Lawrence A; Blasko, Gregory A; Cane, Laurence; Cross, Davina J

    2012-01-01

    In the present case report, we describe the surgical repair of a complete laceration of the anterior tibial tendon using acellular human dermal tissue matrix. A 17-year-old, elite league hockey player was injured in the locker room when a teammate still clad in ice skates stepped on his bare left foot. After evaluation at a local emergency department, the patient presented to our office the next day for additional evaluation. It was determined that surgery would be performed using acellular tissue graft augmentation, followed by physical therapy. Within 7 weeks of the injury, the athlete returned to his original level of activity. At 3 years of follow-up, he was playing Division 1 hockey at the university level. We believe that augmentation of the tendon repair with the grafting material enhanced the tendon tensile strength and promoted ingrowth through vascular channels. This, combined with the patient's dedication to physical therapy, led to excellent recovery in less time than anticipated. PMID:22762944

  2. The influence of platelet-derived products on angiogenesis and tissue repair: a concise update

    PubMed Central

    Martínez, Constanza E.; Smith, Patricio C.; Palma Alvarado, Verónica A.

    2015-01-01

    Platelet degranulation allows the release of a large amount of soluble mediators, is an essential step for wound healing initiation, and stimulates clotting, and angiogenesis. The latter process is one of the most critical biological events observed during tissue repair, increasing the growth of blood vessels in the maturing wound. Angiogenesis requires the action of a variety of growth factors that act in an appropriate physiological ratio to assure functional blood vessel restoration. Platelets release main regulators of angiogenesis: Vascular Endothelial Growth Factors (VEGFs), basic fibroblast growth factor (FGF-2), and Platelet derived growth factors (PDGFs), among others. In order to stimulate tissue repair, platelet derived fractions have been used as an autologous source of growth factors and biomolecules, namely Platelet Rich Plasma (PRP), Platelet Poor Plasma (PPP), and Platelet Rich Fibrin (PRF). The continuous release of these growth factors has been proposed to promote angiogenesis both in vitro and in vivo. Considering the existence of clinical trials currently evaluating the efficacy of autologous PRP, the present review analyses fundamental questions regarding the putative role of platelet derived fractions as regulators of angiogenesis and evaluates the possible clinical implications of these formulations. PMID:26539125

  3. Hiatal Hernia Repair with Gore Bio-A Tissue Reinforcement: Our Experience

    PubMed Central

    Antonino, Agrusa; Giorgio, Romano; Giuseppe, Frazzetta; Giovanni, De Vita; Silvia, Di Giovanni; Daniela, Chianetta; Giuseppe, Di Buono; Vincenzo, Sorce; Gaspare, Gulotta

    2014-01-01

    Type I hiatal hernia is associated with gastroesophageal reflux disease (GERD) in 50–90% of cases. Several trials strongly support surgery as an effective alternative to medical therapy. Today, laparoscopic fundoplication is considered as the procedure of choice. However, primary laparoscopic hiatal hernia repair is associated with upto 42% recurrence rate. Mesh reinforcement of the crural closure decreases the recurrence but can lead to complications, above all nonabsorbable ones. We experiment a new totally absorbable mesh by Gore. Case. We present a case of a 65-year-old female patient with a 6-year classic history of GERD. Endoscopy revealed a large hiatal hernia and esophagitis. pH study was positive for acid reflux; esophageal manometry revealed LES intrathoracic dislocation. With laparoscopic approach, the hiatal hernia defect was identified and primarily repaired, by crural closure. Gore Bio-A Tissue Reinforcement was trimmed to fit the defect accommodating the esophagus. Nissen fundoplication was performed. Result. Bio-A mesh was easily placed laparoscopically. It has good handling and could be cut and tailored intraoperatively for optimal adaptation. There were no short-term complications. Conclusion. Crural closure reinforcement can be done readily with this new totally absorbable mesh replaced by soft tissue over six months. However, further data and studies are needed to evaluate long-term outcomes. PMID:24864221

  4. Hiatal hernia repair with gore bio-a tissue reinforcement: our experience.

    PubMed

    Antonino, Agrusa; Giorgio, Romano; Giuseppe, Frazzetta; Giovanni, De Vita; Silvia, Di Giovanni; Daniela, Chianetta; Giuseppe, Di Buono; Vincenzo, Sorce; Gaspare, Gulotta

    2014-01-01

    Type I hiatal hernia is associated with gastroesophageal reflux disease (GERD) in 50-90% of cases. Several trials strongly support surgery as an effective alternative to medical therapy. Today, laparoscopic fundoplication is considered as the procedure of choice. However, primary laparoscopic hiatal hernia repair is associated with upto 42% recurrence rate. Mesh reinforcement of the crural closure decreases the recurrence but can lead to complications, above all nonabsorbable ones. We experiment a new totally absorbable mesh by Gore. Case. We present a case of a 65-year-old female patient with a 6-year classic history of GERD. Endoscopy revealed a large hiatal hernia and esophagitis. pH study was positive for acid reflux; esophageal manometry revealed LES intrathoracic dislocation. With laparoscopic approach, the hiatal hernia defect was identified and primarily repaired, by crural closure. Gore Bio-A Tissue Reinforcement was trimmed to fit the defect accommodating the esophagus. Nissen fundoplication was performed. Result. Bio-A mesh was easily placed laparoscopically. It has good handling and could be cut and tailored intraoperatively for optimal adaptation. There were no short-term complications. Conclusion. Crural closure reinforcement can be done readily with this new totally absorbable mesh replaced by soft tissue over six months. However, further data and studies are needed to evaluate long-term outcomes. PMID:24864221

  5. A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair.

    PubMed

    Chen, Xi; Li, Yan; Gu, Ning

    2010-08-01

    A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair. PMID:20683132

  6. Objective assessment of endogenous collagen in vivo during tissue repair by laser induced fluorescence.

    PubMed

    Prabhu, Vijendra; Rao, Satish B S; Fernandes, Edward Mark; Rao, Anuradha C K; Prasad, Keerthana; Mahato, Krishna K

    2014-01-01

    Collagen, a triple helical protein with the primary role of mechanical function, provides tensile strength to the skin, and plays a pivotal task in tissue repair. During tissue regeneration, collagen level increases gradually and therefore, monitoring of such changes in vivo by laser induced fluorescence was the main objective behind the present study. In order to accomplish this, 15 mm diameter excisional wounds were created on six to eight week old Swiss albino mice. The collagen deposition accelerated upon irradiation of single exposure of 2 J/cm2 He-Ne laser dose immediately after wounding was recorded by laser induced autofluorescence in vivo along with un-illuminated and un-wounded controls. Autofluorescence spectra were recorded for each animal of the experimental groups on 0, 5, 10, 30, 45 and 60 days post-wounding, by exciting the granulation tissue/skin with 325 nm He-Cd laser. The variations in the average collagen intensities from the granulation tissue/skin of mice were inspected as a function of age and gender. Further, the spectral findings of the collagen synthesis in wound granulation tissue/un-wounded skin tissues were validated by Picro-Sirius red- polarized light microscopy in a blinded manner through image analysis of the respective collagen birefringence. The in vivo autofluorescence studies have shown a significant increase in collagen synthesis in laser treated animals as compared to the un-illuminated controls. Image analysis of the collagen birefringence further authenticated the ability of autofluorescence in the objective monitoring of collagen in vivo. Our results clearly demonstrate the potential of laser induced autofluorescence in the monitoring of collegen synthesis during tissue regeneration, which may have clinical implications. PMID:24874229

  7. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  8. Takotsubo Cardiomyopathy in an Adult Woman With Repaired Tetralogy of Fallot.

    PubMed

    Nguyen, Lan T; Schelbert, Erik B; Cook, Stephen C

    2016-05-01

    Takotsubo cardiomyopathy is a reversible form of cardiomyopathy rarely reported in the adult congenital patient. We describe a case of a 49-year-old woman with repaired tetralogy of Fallot who presented with acute dyspnea. A 12-lead electrocardiogram revealed diffuse anterolateral T-wave inversion suggestive of myocardial ischemia. Cardiac catheterization was performed, demonstrating angiographically normal coronary arteries. A cardiovascular magnetic resonance examination showed apical akinesis with associated myocardial edema, but no myocardial damage on late gadolinium enhancement imaging, which is a characteristic of Takotsubo cardiomyopathy. The patient was treated medically. A follow-up echocardiogram demonstrated normalization of left ventricular systolic function and apical wall motion abnormalities. PMID:26701619

  9. Shouldice inguinal hernia repair in the male adult: the gold standard? A multicenter controlled trial in 1578 patients.

    PubMed Central

    Hay, J M; Boudet, M J; Fingerhut, A; Poucher, J; Hennet, H; Habib, E; Veyrières, M; Flamant, Y

    1995-01-01

    BACKGROUND: Hernia repair is the second most frequently performed operation in France and in the United States, the prevalence being 36 for every 1000 males. Lowering the recurrence rate by 1% would mean 1000 fewer operations for hernia repair per year in France. METHODS: Between 1983 and 1989, 1578 adult males with a total of 1706 nonrecurrent inguinal hernias were prospectively and randomly allotted to undergo either a Bassini's repair, Cooper's ligament, or Shouldice repair with polypropylene or a Shouldice repair with stainless steel for determination of which technique was associated with the lowest recurrence rate. Fifty-nine hernia repairs were withdrawn after inclusion. Of the 1647 remaining hernias, 52.2% were indirect, 25.6% were direct, and 23.2% were combined. Patients were seen every 6 months for 3 years and then every year. Median follow-up was 5 years 8 months (range, 3 months-8.5 years). RESULTS: At 8.5 years, 5.6% of hernias were lost to follow-up. Ninety-seven hernia repairs failed, 50% during the first 2 years. The actuarial recurrence rate was 7.94% at 8.5 years. The Shouldice repair (stainless steel or polypropylene) was associated with fewer recurrences (6.1%) than either the Bassini's (8.6%) or Cooper's ligament repair (11.2%) technique (p < 0.001). This difference remained significant even when the maximal bias test was used. Fewer recurrences (5.9%) were observed with the stainless steel wire Shouldice repair than with polypropylene version (6.5%), but the difference was not significant. CONCLUSIONS: Shouldice hernia repair provides the patient with the best chances of nonrecurrence regardless of the anatomical type of hernia. The Shouldice hernia repair should be the gold standard for inguinal hernia repair in men and serves as the basis for comparison with all other techniques, be they prosthetic or laparoscopic. PMID:8526578

  10. Fetal and adult fibroblasts display intrinsic differences in tendon tissue engineering and regeneration

    PubMed Central

    Tang, Qiao-Mei; Chen, Jia Lin; Shen, Wei Liang; Yin, Zi; Liu, Huan Huan; Fang, Zhi; Heng, Boon Chin; Ouyang, Hong Wei; Chen, Xiao

    2014-01-01

    Injured adult tendons do not exhibit optimal healing through a regenerative process, whereas fetal tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered tendons. Our results demonstrated that FFs had more potential for tendon tissue engineering, as shown by higher levels of tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult tendon healing. This may assist in the development of future strategies to treat tendon injuries. PMID:24992450

  11. Switching roles: the functional plasticity of adult tissue stem cells.

    PubMed

    Wabik, Agnieszka; Jones, Philip H

    2015-05-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  12. Switching roles: the functional plasticity of adult tissue stem cells

    PubMed Central

    Wabik, Agnieszka; Jones, Philip H

    2015-01-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  13. Postoperative residua and sequelae in adults with repaired tetralogy of Fallot.

    PubMed

    Masuda, Munetaka

    2016-07-01

    Postoperative residua and sequelae after repair of tetralogy of Fallot in adults became one of the major concerns in the field of adult congenital heart disease. Right heart failure and arrhythmia can result fatal, and are considered to be related dilated right ventricle due to pulmonary valve regurgitation. Although precise indication of pulmonary valve replacement (PVR) is still not established, right ventricular end-diastolic volume index less than 150-170 ml/m(2) and right ventricular end systolic volume index less than 82-90 ml/m(2) may be border line for RV remodeling after PVR. Biological prosthetic valve is generally used at the pulmonary position. PMID:27116601

  14. Adult stem cell plasticity: will engineered tissues be rejected?

    PubMed Central

    Fang, Te-Chao; Alison, Malcolm R; Wright, Nicholas A; Poulsom, Richard

    2004-01-01

    The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. PMID:15255965

  15. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells.

    PubMed

    Regnell, Christine Elisabeth; Hildrestrand, Gunn Annette; Sejersted, Yngve; Medin, Tirill; Moldestad, Olve; Rolseth, Veslemøy; Krokeide, Silje Zandstra; Suganthan, Rajikala; Luna, Luisa; Bjørås, Magnar; Bergersen, Linda H

    2012-09-27

    Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance. PMID:22959434

  16. Safety of Intra-Articular Use of Atelocollagen for Enhanced Tissue Repair

    PubMed Central

    Magarian, Elise M; Vavken, Patrick; Connolly, Susan A; Mastrangelo, Ashley N; Murray, Martha M

    2012-01-01

    Collagen is an important biomaterial in intra-articular tissue engineering, but there are unanswered questions about its safety. We hypothesize that the addition of type-I-collagen for primary repair of the Anterior Cruciate Ligament (ACL) might result in a local and systemic reaction in a porcine model after 15 weeks as demonstrated by joint effusion, synovial thickening, elevated intraarticular and systemic leukocyte counts. Further, this reaction might be aggravated by the addition of a platelet concentrate. Eighteen porcine ACLs were transected and repaired with either sutures (n=6), a collagen sponge (n=6), or a collagen-platelet-composite (CPC; n=6). Twelve intact contralateral knees served as controls (n=12). No significant synovial thickening or joint effusion was seen in the collagen-treated knees. Synovial fluid leukocyte counts showed no significant differences between surgically treated and intact knees, and no differences were seen in leukocyte counts of the peripheral blood. The addition of a platelet concentrate to the knee joint resulted in lower serum levels of IL-1β, but serum levels of TNF-α were not significantly different between groups. In conclusion, the presence of collagen, with or without added platelets, did not increase the local or systemic inflammatory reactions following surgery, suggesting that Type I collagen is safe to use in the knee joint. PMID:22802918

  17. Lin− Cells Mediate Tissue Repair by Regulating MCP-1/CCL-2

    PubMed Central

    Schatteman, Gina C.; Awad, Ola; Nau, Eric; Wang, Chunlin; Jiao, Chunhua; Tomanek, Robert J.; Dunnwald, Martine

    2010-01-01

    Exogenous bone marrow-derived cells (BMDCs) are promising therapeutic agents for the treatment of tissue ischemia and traumatic injury. However, until we identify the molecular mechanisms that underlie their actions, there can be no rational basis for the design of therapeutic strategies using BMDCs. The pro-healing effects of BMDCs are apparent very shortly after treatment, which suggests that they may exert their effects by the modulation of acute inflammation. We investigated this hypothesis by taking advantage of the fact that BMDCs from healthy, young, but not obese, diabetic mice stimulate vascular growth. By comparing both in vitro secretion and in vivo local induction of acute phase inflammatory cytokines by these cells, we identified monocyte chemoattractant factor 1 and tumor necrosis factor α as potential mediators of BMDC-induced tissue repair. In vivo analysis of BMDC-treated ischemic limbs and cutaneous wounds revealed that the production of monocyte chemoattractant factor 1 by exogenous and endogenous BMDCs is essential for BMDC-mediated vascular growth and tissue healing, while the inability of BMDCs to produce tumor necrosis factor α appears to play a lesser but still meaningful role. Thus, measurements of the secretion of cytokines by BMDCs may allow us to identify a priori individuals who would or would not be good candidates for BMDC-based therapies. PMID:20813969

  18. HDAC inhibition radiosensitizes human normal tissue cells and reduces DNA Double-Strand Break repair capacity.

    PubMed

    Purrucker, Jan C; Fricke, Andreas; Ong, Mei Fang; Rübe, Christian; Rübe, Claudia E; Mahlknecht, Ulrich

    2010-01-01

    HDAC inhibitors (HDACi) are gaining increasing attention in the treatment of cancer, particularly in view of their therapeutic effectiveness and assumed mild toxicity profile. While numerous studies have investigated the role of HDACi in tumor cells, little is known about their effects on normal tissue cells. We studied the effect of suberoylanilide hydroxamic acid (SAHA), MS275, sodium-butyrate and valproic acid in healthy human fibroblasts and found HDACi-treatment to go along with increased radiosensitivity and reduced DSB repair capacity. In view of the potential genotoxic effects of HDACi-treatment, particularly when being administered long-term for chronic disease or when given to children, to women of childbearing age or their partners or in combination with radiotherapy, an extensive education of patients and prescribing physicians as well as a stringent definition of clinical indications is urgently required. PMID:19956891

  19. DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma.

    PubMed

    Rajaraman, Preetha; Hutchinson, Amy; Wichner, Sara; Black, Peter M; Fine, Howard A; Loeffler, Jay S; Selker, Robert G; Shapiro, William R; Rothman, Nathaniel; Linet, Martha S; Inskip, Peter D

    2010-01-01

    Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case-control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR(CT/TT) = 3.5; 95% confidence interval: 1.8-6.9; P(trend) .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P(trend) .01); MUTYH rs3219466 (P(trend) .02), and PCNA rs25406 (P(trend) .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P(trend) .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P(trend) .03) and ERCC5 rs17655 (P(trend) .05) variants and decreased for the PARP1 rs1136410 (P(trend) .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P(trend) .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma. PMID:20150366

  20. A biocompatible hybrid material with simultaneous calcium and strontium release capability for bone tissue repair.

    PubMed

    Almeida, J Carlos; Wacha, András; Gomes, Pedro S; Alves, Luís C; Fernandes, M Helena Vaz; Salvado, Isabel M Miranda; Fernandes, M Helena R

    2016-05-01

    The increasing interest in the effect of strontium in bone tissue repair has promoted the development of bioactive materials with strontium release capability. According to literature, hybrid materials based on the system PDMS-SiO2 have been considered a plausible alternative as they present a mechanical behavior similar to the one of the human bone. The main purpose of this study was to obtain a biocompatible hybrid material with simultaneous calcium and strontium release capability. A hybrid material, in the system PDMS-SiO2-CaO-SrO, was prepared with the incorporation of 0.05 mol of titanium per mol of SiO2. Calcium and strontium were added using the respective acetates as sources, following a sol-gel technique previously developed by the present authors. The obtained samples were characterized by FT-IR, solid-state NMR, and SAXS, and surface roughness was analyzed by 3D optical profilometry. In vitro studies were performed by immersion of the samples in Kokubo's SBF for different periods of time, in order to determine the bioactive potential of these hybrids. Surfaces of the immersed samples were observed by SEM, EDS and PIXE, showing the formation of calcium phosphate precipitates. Supernatants were analyzed by ICP, revealing the capability of the material to simultaneously fix phosphorus ions and to release calcium and strontium, in a concentration range within the values reported as suitable for the induction of the bone tissue repair. The material demonstrated to be cytocompatible when tested with MG63 osteoblastic cells, exhibiting an inductive effect on cell proliferation and alkaline phosphatase activity. PMID:26952443

  1. Tissue repair genes: the TiRe database and its implication for skin wound healing

    PubMed Central

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E.

    2016-01-01

    Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org. PMID:27049721

  2. Tissue repair genes: the TiRe database and its implication for skin wound healing.

    PubMed

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E

    2016-04-19

    Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org. PMID:27049721

  3. Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair.

    PubMed

    Varga, Tamas; Mounier, Rémi; Horvath, Attila; Cuvellier, Sylvain; Dumont, Florent; Poliska, Szilard; Ardjoune, Hamida; Juban, Gaëtan; Nagy, Laszlo; Chazaud, Bénédicte

    2016-06-01

    Macrophage gene expression determines phagocyte responses and effector functions. Macrophage plasticity has been mainly addressed in in vitro models that do not account for the environmental complexity observed in vivo. In this study, we show that microarray gene expression profiling revealed a highly dynamic landscape of transcriptomic changes of Ly6C(pos)CX3CR1(lo) and Ly6C(neg)CX3CR1(hi) macrophage populations during skeletal muscle regeneration after a sterile damage. Systematic gene expression analysis revealed that the time elapsed, much more than Ly6C status, was correlated with the largest differential gene expression, indicating that the time course of inflammation was the predominant driving force of macrophage gene expression. Moreover, Ly6C(pos)/Ly6C(neg) subsets could not have been aligned to canonical M1/M2 profiles. Instead, a combination of analyses suggested the existence of four main features of muscle-derived macrophages specifying important steps of regeneration: 1) infiltrating Ly6C(pos) macrophages expressed acute-phase proteins and exhibited an inflammatory profile independent of IFN-γ, making them damage-associated macrophages; 2) metabolic changes of macrophages, characterized by a decreased glycolysis and an increased tricarboxylic acid cycle/oxidative pathway, preceded the switch to and sustained their anti-inflammatory profile; 3) Ly6C(neg) macrophages, originating from skewed Ly6C(pos) cells, actively proliferated; and 4) later on, restorative Ly6C(neg) macrophages were characterized by a novel profile, indicative of secretion of molecules involved in intercellular communications, notably matrix-related molecules. These results show the highly dynamic nature of the macrophage response at the molecular level after an acute tissue injury and subsequent repair, and associate a specific signature of macrophages to predictive specialized functions of macrophages at each step of tissue injury/repair. PMID:27183604

  4. Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome

    PubMed Central

    Singh, Rabindra P.; Grimer, Robert J.; Bhujel, Nabina; Carter, Simon R.; Tillman, Roger M.; Abudu, Adesegun

    2008-01-01

    We have retrospectively analysed the experience of a musculoskeletal oncological unit in the management of adult head and neck soft tissue sarcomas from 1990 to 2005. Thirty-six patients were seen, of whom 24 were treated at this unit, the remainder only receiving advice. The median age of the patients was 46 years. Most of the sarcomas were deep and of high or intermediate grade with a median size of 5.5 cm. Eleven different histological subtypes were identified. Wide excision was possible only in 21% of the cases. 42% of the patients developed local recurrence and 42% developed metastatic disease usually in the lungs. Overall survival was 49% at 5 years. Tumour size was the most important prognostic factor. Adult head and neck soft tissue sarcomas have a high mortality rate with a high risk of local recurrence and metastatic disease. The rarity of the disease would suggest that centralisation of care could lead to increased expertise and better outcomes. PMID:18382622

  5. Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

    PubMed Central

    2012-01-01

    Background All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP) which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR). Results mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus-host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP, where the majority of genes were differentially expressed, the enrichment (adjusted P < 0.1) of tissue repair and proliferative activity pathways was observed. Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions The results of this study reveal an early activation of the immune

  6. Evaluation of a new range of light-activated surgical adhesives for tissue repair in a porcine model

    NASA Astrophysics Data System (ADS)

    Riley, Jill N.; Hodges, Diane E.; March, Keith L.; McNally-Heintzelman, Karen M.

    2001-05-01

    An in vitro study was conducted to determine the feasibility of using a new range of light-activated surgical adhesives for incision repair in a wide range of tissue types. Biodegradable polymer membranes of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and salt particles using a solvent-casting and particulate- leaching technique. The porous membranes were doped with protein solder composed of 50%(w/v) bovine serum albumin solder and 0.5 mg/ml indocyanine green (ICG) dye mixed in deionized water. Tissue incisions were repaired using the surgical adhesive in conjunction with an 805-nm diode laser. Nine organs were tested ranging from skin to liver to the small intestine, as well as the coronary, pulmonary, carotid, femoral and splenetic arteries. Acute breaking strengths were measured and the data were analyzed by Student's T-test. Repairs formed on the small intestine were most successful followed by spleen, atrium, kidney, muscle and skin. The strongest vascular repairs were achieved in the carotid artery and femoral artery. The new surgical adhesive could possibly be used as a simple and effective method to stop bleeding and repair tissue quickly in an emergency situation, or as a substitute to mechanical staples or sutures in many clinical applications.

  7. Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

    PubMed Central

    2013-01-01

    Background In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. PMID:23324433

  8. Double-Strand Break Repair by Interchromosomal Recombination: An In Vivo Repair Mechanism Utilized by Multiple Somatic Tissues in Mammals

    PubMed Central

    White, Ryan R.; Sung, Patricia; Vestal, C. Greer; Benedetto, Gregory; Cornelio, Noelle; Richardson, Christine

    2013-01-01

    Homologous recombination (HR) is essential for accurate genome duplication and maintenance of genome stability. In eukaryotes, chromosomal double strand breaks (DSBs) are central to HR during specialized developmental programs of meiosis and antigen receptor gene rearrangements, and form at unusual DNA structures and stalled replication forks. DSBs also result from exposure to ionizing radiation, reactive oxygen species, some anti-cancer agents, or inhibitors of topoisomerase II. Literature predicts that repair of such breaks normally will occur by non-homologous end-joining (in G1), intrachromosomal HR (all phases), or sister chromatid HR (in S/G2). However, no in vivo model is in place to directly determine the potential for DSB repair in somatic cells of mammals to occur by HR between repeated sequences on heterologs (i.e., interchromosomal HR). To test this, we developed a mouse model with three transgenes—two nonfunctional green fluorescent protein (GFP) transgenes each containing a recognition site for the I-SceI endonuclease, and a tetracycline-inducible I-SceI endonuclease transgene. If interchromosomal HR can be utilized for DSB repair in somatic cells, then I-SceI expression and induction of DSBs within the GFP reporters may result in a functional GFP+ gene. Strikingly, GFP+ recombinant cells were observed in multiple organs with highest numbers in thymus, kidney, and lung. Additionally, bone marrow cultures demonstrated interchromosomal HR within multiple hematopoietic subpopulations including multi-lineage colony forming unit–granulocyte-erythrocyte-monocyte-megakaryocte (CFU-GEMM) colonies. This is a direct demonstration that somatic cells in vivo search genome-wide for homologous sequences suitable for DSB repair, and this type of repair can occur within early developmental populations capable of multi-lineage differentiation. PMID:24349572

  9. The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

    NASA Astrophysics Data System (ADS)

    Zhang, Ning

    A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility

  10. Visible Light Crosslinking of Methacrylated Hyaluronan Hydrogels for Injectable Tissue Repair

    PubMed Central

    Fenn, Spencer L.; Oldinski, Rachael A.

    2015-01-01

    Tissue engineering hydrogels are primarily cured in situ using ultraviolet (UV) radiation which limits the use of hydrogels as drug or cell carriers. Visible green light activated crosslinking systems are presented as a safe alternative to UV photocrosslinked hydrogels, without compromising material properties such as viscosity and stiffness. The objective of this study was to fabricate and characterize photocrosslinked hydrogels with well-regulated gelation kinetics and mechanical properties for the repair or replacement of soft tissue. An anhydrous methacrylation of hyaluronan (HA) was performed to control the degree of modification (DOM) of HA, verified by 1H-NMR spectroscopy. UV activated crosslinking was compared to visible green light activated crosslinking. While the different photocrosslinking techniques resulted in varied crosslinking times, comparable mechanical properties of UV and green light activated crosslinked hydrogels were achieved using each photocrosslinking method by adjusting time of light exposure. Methacrylated HA (HA-MA) hydrogels of varying molecular weight, DOM and concentration exhibited compressive moduli ranging from 1 kPa to 116 kPa, for UV crosslinking, and 3 kPa to 146 kPa, for green light crosslinking. HA-MA molecular weight and concentration were found to significantly influence moduli values. HA-MA hydrogels did not exhibit any significant cytotoxic affects towards human mesenchymal stem cells. Green light activated crosslinking systems are presented as a viable method to form natural-based hydrogels in situ. PMID:26097172

  11. Design of a Novel Composite H2 S-Releasing Hydrogel for Cardiac Tissue Repair.

    PubMed

    Mauretti, Arianna; Neri, Annalisa; Kossover, Olga; Seliktar, Dror; Nardo, Paolo Di; Melino, Sonia

    2016-06-01

    The design of 3D scaffolds is a crucial step in the field of regenerative medicine. Scaffolds should be degradable and bioresorbable as well as display good porosity, interconnecting pores, and topographic features; these properties favour tissue integration and vascularization. These requirements could be fulfilled by hybrid hydrogels using a combination of natural and synthetic components. Here, the mechanical and biological properties of a polyethylene glycol-fibrinogen hydrogel (PFHy) are improved in order to favour the proliferation and differentiation of human Sca-1(pos) cardiac progenitor cells (hCPCs). PFHys are modified by embedding air- or perfluorohexane-filled bovine serum albumin microbubbles (MBs) and characterized. Changes in cell morphology are observed in MBs-PFHys, suggesting that MBs could enhance the formation of bundles of cells and influence the direction of the spindle growth. The properties of MBs as carriers of active macromolecules are also exploited. For the first time, enzyme-coated MBs have been used as systems for the production of hydrogen sulfide (H2 S)-releasing scaffolds. Novel H2 S-releasing PFHys are produced, which are able to improve the growth of hCPCs. This novel 3D cell-scaffold system will allow the assessment of the effects of H2 S on the cardiac muscle regeneration with its potential applications in tissue repair. PMID:26857526

  12. Genesis of myocardial repair with cardiac progenitor cells and tissue engineering

    PubMed Central

    Sim, Eugene K W; Haider, Husnain Kh; Lila, Nermine; Schussler, Olivier; Chachques, Juan C; Ye, Lei

    2010-01-01

    Background There is mounting evidence to suggest that the heart has regenerative potential in the event of myocardial injury. Recent studies have shown that a resident population of cardiac progenitor cells (CPCs) in the heart contains both vasculogenic and myogenic lineages. CPCs are able to migrate to the site of injury in the heart for participation in the healing process. The resident CPCs in the heart may also be activated through outside pharmacological intervention to promote their participation in the intrinsic repair process. In the light of these characteristics, CPCs provide a logical source for the heart cell therapy. During the regenerative cardiac process, stem cell niches (a specialised environment surrounding stem cells) provide crucial support needed for their maintenance. Discussion Compromised niche function may lead to the selection of stem cells that no longer depend on self-renewal factors produced by its environment. The objective of stem cell transplantation associated with tissue-engineered approaches is to create a new modality in the treatment of heart failure. The use of efficient scaffolds will aid to re-establish a favourable microenvironment for stem cell survival, multiplication, differentiation and function. Cardiac tissue engineering using natural and/or synthetic materials in this regard provides a novel possibility in cardiovascular therapeutics. PMID:27325955

  13. Adult stem cells in bone and cartilage tissue engineering.

    PubMed

    Salgado, António J; Oliveira, João T; Pedro, Adriano J; Reis, Rui L

    2006-09-01

    The progressive increase in life expectancy within the last century has led to the appearance of novel health related problems, some of those within the musculoskeletal field. Among the latter, one can find diseases such as osteoporosis, rheumatoid arthritis and bone cancer, just to mention some of the most relevant. Other related problems are those that arise from serious injuries, often leading to non-recoverable critical size defects. The therapies currently used to treat this type of diseases/injuries are based on the use of pharmaceutical agents, auto/allotransplant and synthetic materials. However, such solutions present a number of inconveniences and therefore, there is a constant search for novel therapeutic solutions. The appearance of a novel field of science called Tissue engineering brought some hope for the solution of the above mentioned problems. In this field, it is believed that by combining a 3D porous template--scaffold--with an adequate cell population, with osteo or chondrogenic potential, it will be possible to develop bone and cartilage tissue equivalents that when implanted in vivo, could lead to the total regeneration of the affected area. This ideal cell population should have a series of properties, namely a high osteo and chondrogenic potential and at the same time, should be easily expandable and maintained in cultures for long periods of time. Due to its natural and intrinsic properties, stem cells are one of the best available cell types. However, after this sentence, the readers may ask, "Which Stem Cells?". During the last 10/15 years, the scientific community witnessed and reported the appearance of several sources of stem cells with both osteo and chondrogenic potential. Therefore, the present review intends to make an overview of data reported on different sources of adult stem cells (bone marrow, periosteum, adipose tissue, skeletal muscle and umbilical cord) for bone and cartilage regenerative medicine, namely those focusing on

  14. Evaluation of adipose-derived stem cells for tissue-engineered muscle repair construct-mediated repair of a murine model of volumetric muscle loss injury.

    PubMed

    Kesireddy, Venu

    2016-01-01

    Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR-MDC constructs as previously reported. PMID:27114706

  15. Evaluation of adipose-derived stem cells for tissue-engineered muscle repair construct-mediated repair of a murine model of volumetric muscle loss injury

    PubMed Central

    Kesireddy, Venu

    2016-01-01

    Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR–MDC constructs as previously reported. PMID:27114706

  16. Comparative potential of juvenile and adult human articular chondrocytes for cartilage tissue formation in three-dimensional biomimetic hydrogels.

    PubMed

    Smeriglio, Piera; Lai, Janice H; Dhulipala, Lakshmi; Behn, Anthony W; Goodman, Stuart B; Smith, Robert L; Maloney, William J; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Regeneration of human articular cartilage is inherently limited and extensive efforts have focused on engineering the cartilage tissue. Various cellular sources have been studied for cartilage tissue engineering including adult chondrocytes, and embryonic or adult stem cells. Juvenile chondrocytes (from donors below 13 years of age) have recently been reported to be a promising cell source for cartilage regeneration. Previous studies have compared the potential of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes. To comprehensively characterize the comparative potential of young, old, and diseased chondrocytes, here we examined cartilage formation by juvenile, adult, and OA chondrocytes in three-dimensional (3D) biomimetic hydrogels composed of poly(ethylene glycol) and chondroitin sulfate. All three human articular chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3 or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were analyzed using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile chondrocytes showed a greater upregulation of chondrogenic gene expression than adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and type II collagen deposition and glycosaminoglycan accumulation were high for juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was observed in the compressive moduli of the cartilage constructs generated by the three different chondrocytes. In conclusion, the juvenile, adult and OA chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D culture model described here may also provide a useful tool to further study the molecular differences among chondrocytes from different stages, which can help elucidate the mechanisms for age-related decline in the intrinsic capacity for cartilage repair. PMID:25054343

  17. Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

    PubMed Central

    Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

    2014-01-01

    Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

  18. Chondroitin sulphate-based 3D scaffolds containing MWCNTs for nervous tissue repair.

    PubMed

    Serrano, María C; Nardecchia, Stefania; García-Rama, Concepción; Ferrer, María L; Collazos-Castro, Jorge E; del Monte, Francisco; Gutiérrez, María C

    2014-02-01

    Nervous tissue lesions are an important social concern due to their increasing prevalence and their high sanitary costs. Their treatment still remains a challenge because of the reduced ability of nervous tissue to regenerate, its intrinsic structural and functional complexity and the rapid formation of fibroglial scars inhibiting neural repair. Herein, we show that 3D porous scaffolds made of chondroitin sulphate (CS), a major regulatory component of the nervous tissue, and multi-walled carbon nanotubes (MWCNTs) are selective substrates for the formation of a viable and neuron-enriched network with a transitory low glial content. Scaffolds have been fabricated by using the ice segregation-induced self-assembly technique and cultured with embryonic neural progenitor cells. Cell adhesion, morphology, viability, neuron/glial differentiation, calcium signaling dynamics, and mitochondrial activity have been studied over time on the scaffolds and compared to appropriate 2D control substrates. Our results indicate the formation of viable cultures enriched in neuron cells for up to 20 days, with ability to display calcium transients and active mitochondria, even in the absence of poly-D-lysine coating. A synergistic neural-permissive signaling from both the scaffold structure and its components (i.e., MWCNTs and CS) is suggested as the major responsible factor for these findings. We anticipate that these scaffolds may serve nerve regeneration if implanted in the acute phase after injury, as it is during the first stages of graft implantation when the most critical sequence of phenomena takes place to drive either nervous regeneration or fibroglial scar formation. The temporary glial inhibition found may be, indeed, beneficial for promoting the formation of neuron-enriched circuits at early phases while guaranteeing posterior glial integration to support longer-term neuron survival and activity. PMID:24290440

  19. Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells.

    PubMed

    Ye, Lei; Haider, Husnain Kh; Sim, Eugene K W

    2006-01-01

    The real promise of a stem cell-based approach for cardiac regeneration and repair lies in the promotion of myogenesis and angiogenesis at the site of the cell graft to achieve both structural and functional benefits. Despite all of the progress and promise in this field, many unanswered questions remain; the answers to these questions will provide the much-needed breakthrough to harness the real benefits of cell therapy for the heart in the clinical perspective. One of the major issues is the choice of donor cell type for transplantation. Multiple cell types with varying potentials have been assessed for their ability to repopulate the infarcted myocardium; however, only the adult stem cells, that is, skeletal myoblasts (SkM) and bone marrow-derived stem cells (BMC), have been translated from the laboratory bench to clinical use. Which of these two cell types will provide the best option for clinical application in heart cell therapy remains arguable. With results pouring in from the long-term follow-ups of previously conducted phase I clinical studies, and with the onset of phase II clinical trials involving larger population of patients, transplantation of stem cells as a sole therapy without an adjunct conventional revascularization procedure will provide a deeper insight into the effectiveness of this approach. The present article discusses the pros and cons of using SkM and BMC individually or in combination for cardiac repair, and critically analyzes the progress made with each cell type. PMID:16380640

  20. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  1. Visible light crosslinking of methacrylated hyaluronan hydrogels for injectable tissue repair.

    PubMed

    Fenn, Spencer L; Oldinski, Rachael A

    2016-08-01

    Tissue engineering hydrogels are primarily cured in situ using ultraviolet (UV) radiation which limits the use of hydrogels as drug or cell carriers. Visible green light activated crosslinking systems are presented as a safe alternative to UV photocrosslinked hydrogels, without compromising material properties such as viscosity and stiffness. The objective of this study was to fabricate and characterize photocrosslinked hydrogels with well-regulated gelation kinetics and mechanical properties for the repair or replacement of soft tissue. An anhydrous methacrylation of hyaluronan (HA) was performed to control the degree of modification (DOM) of HA, verified by (1) H-NMR spectroscopy. UV-activated crosslinking was compared to visible green light activated crosslinking. While the different photocrosslinking techniques resulted in varied crosslinking times, comparable mechanical properties of UV and green light activated crosslinked hydrogels were achieved using each photocrosslinking method by adjusting time of light exposure. Methacrylated HA (HA-MA) hydrogels of varying molecular weight, DOM, and concentration exhibited compressive moduli ranging from 1 kPa to 116 kPa, for UV crosslinking, and 3 kPa to 146 kPa, for green light crosslinking. HA-MA molecular weight and concentration were found to significantly influence moduli values. HA-MA hydrogels did not exhibit any significant cytotoxic effects toward human mesenchymal stem cells. Green light activated crosslinking systems are presented as a viable method to form natural-based hydrogels in situ. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1229-1236, 2016. PMID:26097172

  2. Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.

    PubMed

    Min, Jouha; Choi, Ki Young; Dreaden, Erik C; Padera, Robert F; Braatz, Richard D; Spector, Myron; Hammond, Paula T

    2016-04-26

    Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic. PMID:26923427

  3. Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

    PubMed Central

    Fahy, Niamh; Farrell, Eric; Ritter, Thomas; Ryan, Aideen E.

    2015-01-01

    Osteoarthritis (OA), the most common form of arthritis, is a disabling degenerative joint disease affecting synovial joints and is associated with cartilage destruction, inflammation of the synovial membrane, and subchondral bone remodeling. Inflammation of the synovial membrane may arise secondary to degenerative processes in articular cartilage (AC), or may be a primary occurrence in OA pathogenesis. However, synovial inflammation plays a key role in the pathogenesis and disease progression of OA through the production of pro-inflammatory mediators, and is associated with cartilage destruction and pain. The triggers that initiate activation of the immune response in OA are unknown, but crosstalk between osteoarthritic chondrocytes, cartilage degradation products, and the synovium may act to perpetuate this response. Increasing evidence has emerged highlighting an important role for pro-inflammatory mediators and infiltrating inflammatory cell populations in the progression of the disease. Tissue engineering strategies hold great potential for the repair of damaged AC in an osteoarthritic joint. However, an in-depth understanding of how OA-associated inflammation impacts chondrocyte and progenitor cell behavior is required to achieve efficient cartilage regeneration in a catabolic osteoarthritic environment. In this review, we will discuss the role of inflammation in OA, and investigate novel immune modulation strategies that may prevent disease progression and facilitate successful cartilage regeneration for the treatment of OA. PMID:24950588

  4. Strategies to Stimulate Mobilization and Homing of Endogenous Stem and Progenitor Cells for Bone Tissue Repair

    PubMed Central

    Herrmann, Marietta; Verrier, Sophie; Alini, Mauro

    2015-01-01

    The gold standard for the treatment of critical-size bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies represent an alternative approach. Mesenchymal stem cells (MSCs) have been considered as a source of osteoprogenitor cells. More recently, focus has been placed on the use of endothelial progenitor cells (EPCs), since vascularization is a critical step in bone healing. Although many of these approaches have demonstrated effectiveness for bone regeneration, cell-based therapies require time consuming and cost-expensive in vitro cell expansion procedures. Accordingly, research is becoming increasingly focused on the homing and stimulation of native cells. The stromal cell-derived factor-1 (SDF-1) – CXCR4 axis has been shown to be critical for the recruitment of MSCs and EPCs. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and has been targeted in many studies. Here, we present an overview of the different approaches for delivering homing factors to the defect site by absorption or incorporation to biomaterials, gene therapy, or via genetically manipulated cells. We further review strategies focusing on the stimulation of endogenous cells to support bone repair. Finally, we discuss the major challenges in the treatment of critical-size bone defects and fracture non-unions. PMID:26082926

  5. Egr-1: new conductor for the tissue repair orchestra directs harmony (regeneration) or cacophony (fibrosis).

    PubMed

    Bhattacharyya, Swati; Fang, Feng; Tourtellotte, Warren; Varga, John

    2013-01-01

    Fibroblasts and myofibroblasts are the key effector cells executing physiological tissue repair leading to regeneration on the one hand, and pathological fibrogenesis leading to chronic fibrosing conditions on the other. Recent studies identify the multifunctional transcription factor early growth response-1(Egr-1) as an important mediator of fibroblast activation triggered by diverse stimuli. Egr-1 has potent stimulatory effects on fibrotic gene expression, and aberrant Egr-1 expression or function is associated with animal models of fibrosis and human fibrotic disorders, including emphysema, pulmonary fibrosis, pulmonary hypertension and systemic sclerosis. Pharmacological suppression or genetic targeting of Egr-1 blocks fibrotic responses in vitro and ameliorates experimental fibrosis in the skin and lung. In contrast, Egr-1 appears to act as a negative regulator of hepatic fibrosis in mouse models, suggesting a context-dependent role in fibrosis. The Egr-1-binding protein Nab2 is an endogenous inhibitor of Egr-1-mediated signalling and abrogates the stimulation of fibrotic responses induced by transforming growth factor-β (TGFβ). Moreover, mice deficient in Nab2 show excessive collagen accumulation in the skin. These observations highlight a previously unsuspected fundamental physiological function for the Egr-1-Nab2 signalling axis in regulating fibrogenesis, and suggest that Egr-1 may be a potential novel therapeutic target in human diseases complicated by fibrosis. This review summarizes recent advances in understanding the regulation and complex functional role of Egr-1 and its related proteins and inhibitors in pathological fibrosis. PMID:23132749

  6. OGG1 mRNA expression and incision activity in rats are higher in foetal tissue than in adult liver tissue while 8-oxo-2'-deoxyguanosine levels are unchanged.

    PubMed

    Riis, Bente; Risom, Lotte; Loft, Steffen; Poulsen, Henrik Enghusen

    2002-09-01

    This study was set up to investigate the relationships between the formation and removal of DNA damage in form of 8-oxodeoxyguanosine (8-oxodG) in neonatal (day 16 of gestation) as compared to adult rats. The hypothesis addressed was whether the rapidly dividing foetal tissue has an enhanced requirement of DNA repair providing protection against potentially mutagenic DNA damages such as 8-oxodG. The activity of the primary 8-oxodG-repair protein OGG1 was measured by a DNA incision assay and the expression of OGG1 mRNA was measured by Real-Time PCR normalised to 18S rRNA. The tissue level of 8-oxodG was measured by HPLC-ECD. We found a 2-3-fold increased incision activity in the foetal control tissue, together with a 3-15-fold increase in mRNA of OGG1 as compared to liver tissue from adult rats. The levels of 8-oxodG in the foetal tissue were unaltered as compared to the adult groups. To increase the levels of 8-oxodG, the rats received an injection (i.p.) of the hepatotoxin 2-nitropropane. The compound induced significant levels of 8-oxodG in male rat livers 5h after the injection and in the foetuses 24h after the injection, while the female rats showed no increase in 8-oxodG. The incision activity was slightly depressed in both male and female liver tissue and in the foetal tissue 5h after the injection, but significantly increased from 5 to 24h after the injection. However, it did not reach levels significantly above the control levels. In conclusion, this study confirms that foetal tissue has increased levels of OGG1 mRNA and correspondingly an enhanced incision activity on an 8-oxodG substrate in a crude tissue extract. PMID:12509275

  7. Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth.

    PubMed Central

    Peters, K G; De Vries, C; Williams, L T

    1993-01-01

    Vascular endothelial growth factor (VEGF) is a polypeptide mitogen that stimulates the growth of endothelial cells in vitro and promotes the growth of blood vessels in vivo. We have recently shown that the fms-like receptor tyrosine kinase (flt) is a receptor for VEGF. Here we used in situ hybridization to show that, in adult mouse tissues, the pattern of flt expression was consistent with localization in endothelium. We also show that flt was expressed in endothelium during neovascularization of healing skin wounds and during early vascular development in mouse embryos. Moreover, flt was expressed in populations of embryonic cells from which endothelium is derived such as early yolk sac mesenchyme. The expression of flt in the endothelium of both developing and mature blood vessels suggests that VEGF might regulate endothelial differentiation, blood vessel growth, and vascular repair. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7692439

  8. Alkaline diets favor lean tissue mass in older adults1234

    PubMed Central

    Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa

    2008-01-01

    Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women. PMID:18326605

  9. Adult human adipose tissue contains several types of multipotent cells.

    PubMed

    Tallone, Tiziano; Realini, Claudio; Böhmler, Andreas; Kornfeld, Christopher; Vassalli, Giuseppe; Moccetti, Tiziano; Bardelli, Silvana; Soldati, Gianni

    2011-04-01

    Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria. PMID:21327755

  10. Preparation and Characterization of Biomimetic Hydroxyapatite-Resorbable Polymer Composites for Hard Tissue Repair

    NASA Astrophysics Data System (ADS)

    Hiebner, Kristopher Robert

    Autografts are the orthopedic "gold standard" for repairing bone voids. Autografts are osteoconductive and do not elicit an immune response, but they are in short supply and require a second surgery to harvest the bone graft. Allografts are currently the most common materials used for the repair of segmental defects in hard tissue. Unlike autografts, allografts can cause an undesirable immune response and the possibility of disease transmission is a major concern. As an alternative to the above approaches, recent research efforts have focused on the use of composite materials made from hydroxyapatite (HA) and bioresorbable polymers, such as poly-L-lactide (PLLA). Recent results have shown that the surface hydroxides on HA can initiate the ring opening polymerization (ROP) of L-lactide and other lactones creating a composite with superior interfacial strength. This thesis demonstrates that the surface of porous biologically derived HA substrates, such as coralline HA and trabecular bone, can be used to initiate the ROP of L-lactide and other lactones from the vapor phase. This process increases the strength of the porous scaffold through the deposition of a thin, uniform polymer coating, while maintaining the porous structure. The kinetics of the chemical vapor deposition polymerization (CVDP) are described using a quartz crystal microbalance (QCM). The reaction temperature and monomer vapor pressure are found to affect the rate of the polymerization. Also described in this thesis is the preparation of a porous polymer scaffold that mimics the structure of demineralized bone matrix (DBM). This demineralized bone matrix simulant (DBMS) is created using anorganic bovine bone as a template to initiate the polymerization of various lactones, followed by the removal of the HA scaffold. This material retained its shape and exhibits mechanical properties superior to DBM. Finally it is shown that HA can be used to initiate the ROP of a-caprolactam and the biocompatibility

  11. Effect of Locally Administered Ciliary Neurotrophic Factor on the Survival of Transected and Repaired Adult Sheep Facial Nerve

    PubMed Central

    Al Abri, Rashid; Kolethekkat, Arif Ali; Kelleher, Michael O.; Myles, Lynn M.; Glasby, Michael A.

    2014-01-01

    Objective to determine whether the administration of Ciliary Neurotrophic Factor (CNTF) at the site of repaired facial nerve enhances regeneration in the adult sheep model. Methods Ten adult sheep were divided into 2 groups: control and study group (CNTF group). In the CNTF group, the buccal branch of the facial nerve was transected and then repaired by epineural sutures. CNTF was injected over the left depressor labii maxillaris muscle in the vicinity of the transected and repaired nerve for 28 days under local anesthesia. In the CNTF group, the sheep were again anesthetized after nine months and the site of facial nerve repair was exposed. Detailed electrophysiological, tension experiments and morphometric studies were carried out and then analyzed statistically. Results The skin CV min, refractory period, Jitter and tension parameters were marginally raised in the CNTF group than the control but the difference was statistically insignificant between the two groups. Morphometric indices also did not show any significant changes in the CNTF group. Conclusion CNTF has no profound effect on neuronal regeneration of adult sheep animal model. Keywords CNTF; Neurtrophic factors; Sheep; Facial nerve; Regeneration. PMID:24936272

  12. Adult stem cells from the hyaluronic acid-rich node and duct system differentiate into neuronal cells and repair brain injury.

    PubMed

    Lee, Seung J; Park, Sang H; Kim, Yu I; Hwang, Sunhee; Kwon, Patrick M; Han, In S; Kwon, Byoung S

    2014-12-01

    The existence of a hyaluronic acid-rich node and duct system (HAR-NDS) within the lymphatic and blood vessels was demonstrated previously. The HAR-NDS was enriched with small (3.0-5.0 μm in diameter), adult stem cells with properties similar to those of the very small embryonic-like stem cells (VSELs). Sca-1(+)Lin(-)CD45(-) cells were enriched approximately 100-fold in the intravascular HAR-NDS compared with the bone marrow. We named these adult stem cells "node and duct stem cells (NDSCs)." NDSCs formed colonies on C2C12 feeder layers, were positive for fetal alkaline phosphatase, and could be subcultured on the feeder layers. NDSCs were Oct4(+)Nanog(+)SSEA-1(+)Sox2(+), while VSELs were Oct4(+)Nanog(+)SSEA-1(+)Sox2(-). NDSCs had higher sphere-forming efficiency and proliferative potential than VSELs, and they were found to differentiate into neuronal cells in vitro. Injection of NDSCs into mice partially repaired ischemic brain damage. Thus, we report the discovery of potential adult stem cells that may be involved in tissue regeneration. The intravascular HAR-NDS may serve as a route that delivers these stem cells to their target tissues. PMID:25027245

  13. The integrin-collagen connection--a glue for tissue repair?

    PubMed

    Zeltz, Cédric; Gullberg, Donald

    2016-02-15

    The α1β1, α2β1, α10β1 and α11β1 integrins constitute a subset of the integrin family with affinity for GFOGER-like sequences in collagens. Integrins α1β1 and α2β1 were originally identified on a subset of activated T-cells, and have since been found to be expressed on a number of cell types including platelets (α2β1), vascular cells (α1β1, α2β1), epithelial cells (α1β1, α2β1) and fibroblasts (α1β1, α2β1). Integrin α10β1 shows a distribution that is restricted to mesenchymal stem cells and chondrocytes, whereas integrin α11β1 appears restricted to mesenchymal stem cells and subsets of fibroblasts. The bulk of the current literature suggests that collagen-binding integrins only have a limited role in adult connective tissue homeostasis, partly due to a limited availability of cell-binding sites in the mature fibrillar collagen matrices. However, some recent data suggest that, instead, they are more crucial for dynamic connective tissue remodeling events--such as wound healing--where they might act specifically to remodel and restore the tissue architecture. This Commentary discusses the recent development in the field of collagen-binding integrins, their roles in physiological and pathological settings with special emphasis on wound healing, fibrosis and tumor-stroma interactions, and include a discussion of the most recently identified newcomers to this subfamily--integrins α10β1 and α11β1. PMID:26857815

  14. Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions.

    PubMed

    Bochyńska, A I; Hannink, G; Grijpma, D W; Buma, P

    2016-05-01

    Menisci are crucial structures in the knee joint as they play important functions in load transfer, maintaining joint stability and in homeostasis of articular cartilage. Unfortunately, ones of the most frequently occurring knee injuries are meniscal tears. Particularly tears in the avascular zone of the meniscus usually do not heal spontaneously and lead to pain, swelling and locking of the knee joint. Eventually, after a (partial) meniscectomy, they will lead to osteoarthritis. Current treatment modalities to repair tears and by that restore the integrity of the native meniscus still carry their drawbacks and a new robust solution is desired. A strong tissue adhesive could provide such a solution and could potentially improve on sutures, which are the current gold standard. Moreover, a glue could serve as a carrier for biological compounds known to enhance tissue healing. Only few tissue adhesives, e.g., Dermabond(®) and fibrin glue, are already successfully used in clinical practice for other applications, but are not considered suitable for gluing meniscus tissue due to their sub-optimal mechanical properties or toxicity. There is a growing interest and research field focusing on the development of novel polymer-based tissue adhesives, but up to now, there is no material specially designed for the repair of meniscal tears. In this review, we discuss the current clinical gold standard treatment of meniscal tears and present an overview of new developments in this field. Moreover, we discuss the properties of different tissue adhesives for their potential use in meniscal tear repair. Finally, we formulate recommendations regarding the design criteria of material properties and adhesive strength for clinically applicable glues for meniscal tears. PMID:26970767

  15. Late Results after Repair of Partial Atrioventricular Septal Defect in Adolescents and Adults

    PubMed Central

    Lukács, László; Szántó, György; Kassai, Imre; Lengyel, Mária

    1992-01-01

    From January 1966 through December 1985, 29 adolescents and adults underwent surgical repair of a partial atrioventricular septal defect at our institution. The patients included 20 females and 9 males, whose ages ranged from 16 to 47 years (mean, 27.6 ± 10.1 years). Preoperatively, 24 patients were in New York Heart Association functional class I or II, and 5 were in class III. The pulmonary artery systolic pressure ranged from 22 to 62 mmHg (mean, 38.3 ± 12.7 mmHg). The pulmonary-to-systemic flow ratio ranged from 1.4 to 2.9 (mean, 2.3 ± 0.5). Upon left ventriculography, regurgitation through the left atrioventricular valve was trivial or nonexistent in 4 patients (13.8%), mild in 14 (48.3%), moderate in 10 (34.5%), and severe in 1 patient (3.4%). All patients underwent patch closure of the ostium primum defect, and all but 2 underwent partial or complete suturing of the septal commissure. One patient died within 30 days, for a hospital mortality of 3.4%. The follow-up period ranged from 7 to 25 years (mean, 15.2 ± 5.3 years). Postoperatively, all patients were evaluated with 2-dimensional and Doppler echocardiography. One patient underwent early implantation of a permanent pacemaker for persistent complete heart block. Three patients succumbed to late death 10, 15, and 21 years after operation. Among the 25 long-term survivors, 1 patient required late valve replacement because of severe left atrioventricular valve regurgitation. Nine (37.5%) of the other 24 long-term survivors had little or no regurgitation. Of the 11 patients with moderate-to-severe preoperative left atrioventricular valve regurgitation, 4 had moderate postoperative regurgitation. Seventeen patients had a moderate or severe persistent apical systolic murmur. At the latest follow-up in 1991, 5 (20%) of the 25 long-term survivors had significant arrhythmias. At 25 years, the actuarial survival rate was 78.9% ± 25.6%. All 25 surviving patients were in New York Heart Association class I or II

  16. The vascularized periosteum flap as novel tissue engineering model for repair of cartilage defects.

    PubMed

    Harhaus, Leila; Huang, Jung-Ju; Kao, Shu-Wei; Wu, Yen-Lin; Mackert, Gina Alicia; Höner, Bernd; Cheng, Ming-Huei; Kneser, Ulrich; Cheng, Chao-Min

    2015-06-01

    Periosteum is a promising tissue engineering scaffold in research of cartilage repair; so far however, periosteum transfers have not been realized successfully because of insufficient nourishment of the graft. In a translational approach we, for the first time, designed a vascularized periosteum flap as 'independent' biomaterial with its own blood supply to address this problem and to reconstruct circumscript cartilage defects. In six 3-month-old New Zealand rabbits, a critical size cartilage defect of the medial femur condyle was created and covered by a vascularized periosteum flap pedicled on the saphenous vessels. After 28 days, formation of newly built cartilage was assessed macroscopically, histologically and qualitatively via biomechanical compression testing, as well as on molecular biological level via immunohistochemistry. All wounds healed completely, all joints were stable and had full range of motion. All flaps survived and were perfused through their pulsating pedicles. They showed a stable attachment to the bone, although partially incomplete adherence. Hyaline cartilage with typical columnar cell distribution and positive Collagen II staining was formed in the transferred flaps. Biomechanical testing revealed a significantly higher maximum load than the positive control, but a low elasticity. This study proved that vascularization of the periosteum flap is the essential step for flap survival and enables the flap to transform into cartilage. Reconstruction of circumscript cartilage defects seems to be possible. Although these are the first results out of a pilot project, this technique, we believe, can have a wide range of potential applications and high relevance in the clinical field. PMID:25754287

  17. High-dose mode of mortality in Tribolium: A model system for study of radiation injury and repair in non-proliferative tissues

    SciTech Connect

    Cheng, Chihing Christina.

    1989-01-01

    With appropriate doses of ionizing radiation, both the acute, or lethal-midlethal, dose-independent pattern of mortality, and the hyperacute, dose-dependent pattern, were demonstrated within a single insect genus (Tribolium). This demonstration provides resolution of apparently contradictory reports of insect radiation responses in terms of doses required to cause lethality and those based on survival time as a function of dose. A dose-dependent mortality pattern was elicited in adult Tribolium receiving high doses, viz., 300 Gy or greater; its time course was complete in 10 days, before the dose-independent pattern of mortality began. Visual observations of heavily-irradiated Tribolium suggested neural and/or neuromuscular damage, as had been previously proposed by others for lethally-irradiated wasps, flies, and mosquitoes. Results of experiments using fractionated high doses supported the suggestion that the hyperacute or high-dose mode of death is the result of damage to nonproliferative tissues. Relative resistance of a strain to the hyperacute or high-dose mode of death was not correlated with resistance to the midlethal mode, which is believed to be the result of damage to the proliferative cells of the midgut. Using the high-dose mode of death as a model of radiation damage to nonproliferative tissues, the effects of age, and of a moderate priming dose were assessed. Beetles showed age-related increase in sensitivity to the high-dose mode of death, suggesting a decline in capacity to repair radiation damage to postmitotic tissue. This correlated with a decrease (50%) in the amount of repair reflected in the sparing effect of dose-fractionation (SDF) between the age of 1 to 3 months. The age related increase in radiosensitivity was reduced by a moderate priming dose (40 or 65 Gy) given at a young age.

  18. Left ventricular function in adults with mild pulmonary insufficiency late after Fallot repair

    PubMed Central

    Niezen, R; Helbing, W; van der Wall, E E; van der Geest, R J; Vliegen, H; de Roos, A

    1999-01-01

    OBJECTIVE—To assess left ventricular function in adult Fallot patients with residual pulmonary regurgitation.
SETTING—The radiology department of a tertiary referral centre.
PATIENTS—14 patients with chronic pulmonary regurgitation and right ventricular volume overload after repair of tetralogy of Fallot and 10 healthy subjects were studied using magnetic resonance imaging.
MAIN OUTCOME MEASURES—Biventricular volumes, global biventricular function, and regional left ventricular function were assessed in all subjects.
RESULTS—The amount of pulmonary regurgitation in patients (mean (SD)) was 25 (18)% of forward flow and correlated significantly with right ventricular enlargement (p < 0.05). Left ventricular end diastolic volume was decreased in patients (78 (11) v 88 (10) ml/m2; p < 0.05), ejection fraction was not significantly altered (59 (5)% v 55 (7)%; NS). No significant correlation was found between pulmonary regurgitation and left ventricular function. Overall left ventricular end diastolic wall thickness was significantly lower in patients (5.06 (0.72) v 6.06 (1.06) mm; p < 0.05), predominantly in the free wall. At the apical level, left ventricular systolic wall thickening was 20% higher in Fallot patients (p < 0.05). Left ventricular shape was normal.
CONCLUSIONS—Adult Fallot patients with mild chronic pulmonary regurgitation and subsequent right ventricular enlargement showed a normal left ventricular shape and global function. Although the left ventricular free wall had reduced wall thickness, compensatory hypercontractility of the apex may contribute to preserved global function.


Keywords: left ventricular function; pulmonary insufficiency; tetralogy of Fallot; magnetic resonance imaging PMID:10573497

  19. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    PubMed

    Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis. PMID:21747960

  20. Disrupted G{sub 1} to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2005-09-01

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G{sub 0} to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G{sub 1} to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes.

  1. Effects of implantation of three-dimensional engineered bone tissue with a vascular-like structure on repair of bone defects

    NASA Astrophysics Data System (ADS)

    Nishi, Masanori; Matsumoto, Rena; Dong, Jian; Uemura, Toshimasa

    2012-12-01

    Previously, to create an implantable bone tissue associated with blood vessels, we co-cultured rabbit bone marrow mesenchymal stem cells (MSCs) with MSC-derived endothelial cells (ECs) within a porous polylactic acid-based scaffold utilizing a rotating wall vessel (RWV) bioreactor. Here, this engineered tissue was orthotopically implanted into defects made in femurs of immunodeficient rats, and histological analysis were carried out to examine the repair of the damage and the formation of bone around the implant. The bone defects were better repaired in the implanted group than control group after 3 weeks. The results indicate that the engineered bone could repair bone defects.

  2. In-situ crosslinkable and self-assembling elastin-like polypeptide block copolymers for cartilage tissue repair

    NASA Astrophysics Data System (ADS)

    Lim, Dong Woo

    This work describes the development of genetically engineered elastin-like polypeptide (ELP) block copolymers as in-situ gelling scaffolds for cartilage tissue repair. The central hypothesis underlying this work is that ELP based biopolymers can be exploited as injectable biomaterials by rapid chemical crosslinking. To prove this, gene libraries encoding ELP having different molecular weights and amino acid sequences, and ELP block copolymers composed of various ELP blocks having diverse amino acid composition, length, and phase transition behavior were synthesized by recursive directional ligation, expressed in E. Coli and purified by inverse transition cycling. Mannich-type condensation of hydroxymethylphosphines (HMPs) with primary- and secondary-amines of amino acids was developed as a new crosslinking method of polypeptides. Chemically crosslinked ELP hydrogels were formed rapidly in an aqueous solution by reaction of ELPs containing periodic lysine residues with HMPs. The crosslinking density and mechanical property of the ELP hydrogels were controlled at the sequence level by varying the Lys density in ELPs composed of mono-block as well as by segregation of the Lys residues within specific blocks of tri-block architectures. Fibroblasts embedded in ELP hydrogels survived the crosslinking process and were viable after in vitro culture for at least 3 days. The DNA content of fibroblasts within the tri-block gels was significantly higher than that in the mono-block gels at day 3. These results suggest that the HMP crosslinked ELP block copolymer hydrogels show finely tuned mechanical properties and different microenvironments for cell viability as well as potential as in-situ crosslinkable biopolymers for tissue repair applications with load-bearing environments. As an alternative, rheological behavior of the ELP block copolymers and ELP-grafted hyaluronic acids (HAs) as artificial extracellular matrices (ECMs) showed that they were thermally aggregated into

  3. Tissue-Specific Effects of Valproic Acid on DNA Repair Genes and Apoptosis in Postimplantation Mouse Embryos

    PubMed Central

    Lamparter, Christina; Winn, Louise M.

    2014-01-01

    Exposure to the anticonvulsant drug valproic acid (VPA) is associated with an increased risk of congenital malformations. Although the mechanisms contributing to its teratogenicity are poorly understood, VPA has been shown to induce DNA double strand breaks (DSB) and to increase homologous recombination in vitro. The objective of the present study was to determine whether in utero exposure to VPA alters the frequency of intrachromosomal recombination and the expression of several genes involved in DSB repair in pKZ1 mouse embryos. Pregnant pKZ1 transgenic mice (GD 9.0) were administered VPA (500 mg/kg s.c.) and embryos were extracted and microdissected into the head, heart, and trunk regions 1, 3, 6, and 24 h after injection. Quantitative PCR was used to measure the tissue-specific expression of lacZ, a surrogate measure of recombination, Xrcc4, Rad51, Brca1, and Brca2, with Western blotting used to quantify Rad51, cleaved caspase-3 and cleaved-PARP protein. Increased recombination was only observed in the embryonic head following 6-h VPA exposure. VPA had no effect on Xrcc4 expression. Rad51, Brca1, and Brca2 expression rapidly decreased in head and trunk tissues after 1-h VPA exposure, followed by a subsequent increase in all tissues, although it was generally attenuated in the head and not due to differences in endogenous levels. Cleaved caspase-3 and cleaved-PARP expression was increased in all tissues 3 h following VPA exposure. This study indicates that the tissue-specific expression of several genes involved in DSB repair is altered following exposure to VPA and may be contributing to increased apoptosis. PMID:24913804

  4. Laser scanning microscopy as a means to assess the augmentation of tissue repair by exposition of wounds to tissue tolerable plasma

    NASA Astrophysics Data System (ADS)

    Vandersee, Staffan; Richter, Heike; Lademann, Jürgen; Beyer, Marc; Kramer, Axel; Knorr, Fanny; Lange-Asschenfeldt, Bernhard

    2014-11-01

    Confocal laser scan microscopy (CLSM) has emerged as a tool for in vivo assessment of cutaneous conditions. In particular, its use in wound healing assessment has increasingly moved into focus. In this context, the application of tissue tolerable plasma (TTP) for wound treatment has recently become one of the most innovative therapeutic modalities. We analyzed wound healing parameters such as area decline and histomorphological characteristics of tissue repair in six subjects with vacuum-generated wounds on the forearm with a four-armed design: (A) no treatment, (B) treatment with TTP, (C) treatment with octenidine, and (D) sequential treatment with TTP and octenidine. Assessment of the wounds was conducted during six visits over the course of two weeks. The wounds were analyzed by photography and CLSM. TTP treatment led to a more rapid area decline that was statistically significant in comparison to other treatment groups. Besides mild pain, it was well tolerated. Morphologically, wound healing was found to initiate from the edges with the formation of dendritic structures consisting of keratinocytes. CLSM is a valuable tool for assessing the dynamics of wound healing. TTP, for reasons that still need to be investigated, can accelerate wound repair.

  5. Traditional native tissue versus mesh-augmented pelvic organ prolapse repairs: providing an accurate interpretation of current literature.

    PubMed

    Stanford, E J; Cassidenti, A; Moen, M D

    2012-01-01

    The objective of this paper was to review the literature on pelvic organ prolapse (POP) and compare the success of traditional/native tissue versus mesh-augmented repairs. A comprehensive literature review was performed using PubMed and bibliography searches to compare the anatomic success rates of native tissue (NT) and mesh-augmented (MA) prolapse repairs and to analyze outcome measures used to report success rates. Articles were included if anatomic outcomes were stated for the specific compartment of interest and included both prospective and retrospective studies. The published success rates for NT repairs versus MA repairs by anterior, posterior, or apical compartments are reported. When continence is used as the primary outcome measure, anterior NT has a success rate of 54%. Anterior NT success is as low as 30% in some studies, but generally is 88-97% when prolapse is the primary outcome particularly if apical support is included. This compares to the 87-96% success reported for anterior MA. Posterior NT success is 54-81%, which is lower than the 92-97% reported for posterior MA when prolapse is the outcome measure. The success rates for apical NT are 97-98% for uterosacral ligament suspension and 96% for sacrospinous ligament suspension, which compare favorably to sacrocolpopexy (91-100%). There are some differences in the complications reported for NT and MA. The rate of complications is approximately 8% for NT and is reported at 0-19% for MA. The higher rate for MA is largely due to mesh erosion/exposure. When similar outcome measures are compared, the published anatomic success rates of POP of anterior and apical compartmental surgery are similar for NT and MA repairs. There may be a higher rate of complications noted for mesh implantation. POP surgery is complex, and both NT and MA techniques require skills to perform proper compartmental reconstruction. An understanding of the published literature and knowledge of individual surgeon factors are

  6. Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of osteochondral repair tissue by using electrospinning and FDM techniques.

    PubMed

    Schumann, Detlef; Ekaputra, Andrew K; Lam, Christopher X F; Hutmacher, Dietmar W

    2007-01-01

    Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue. PMID:18085205

  7. Debra-mediated Ci degradation controls tissue homeostasis in Drosophila adult midgut.

    PubMed

    Li, Zhouhua; Guo, Yueqin; Han, Lili; Zhang, Yan; Shi, Lai; Huang, Xudong; Lin, Xinhua

    2014-02-11

    Adult tissue homeostasis is maintained by resident stem cells and their progeny. However, the underlying mechanisms that control tissue homeostasis are not fully understood. Here, we demonstrate that Debra-mediated Ci degradation is important for intestinal stem cell (ISC) proliferation in Drosophila adult midgut. Debra inhibition leads to increased ISC activity and tissue homeostasis loss, phenocopying defects observed in aging flies. These defects can be suppressed by depleting Ci, suggesting that increased Hedgehog (Hh) signaling contributes to ISC proliferation and tissue homeostasis loss. Consistently, Hh signaling activation causes the same defects, whereas depletion of Hh signaling suppresses these defects. Furthermore, the Hh ligand from multiple sources is involved in ISC proliferation and tissue homeostasis. Finally, we show that the JNK pathway acts downstream of Hh signaling to regulate ISC proliferation. Together, our results provide insights into the mechanisms of stem cell proliferation and tissue homeostasis control. PMID:24527387

  8. Debra-Mediated Ci Degradation Controls Tissue Homeostasis in Drosophila Adult Midgut

    PubMed Central

    Li, Zhouhua; Guo, Yueqin; Han, Lili; Zhang, Yan; Shi, Lai; Huang, Xudong; Lin, Xinhua

    2014-01-01

    Summary Adult tissue homeostasis is maintained by resident stem cells and their progeny. However, the underlying mechanisms that control tissue homeostasis are not fully understood. Here, we demonstrate that Debra-mediated Ci degradation is important for intestinal stem cell (ISC) proliferation in Drosophila adult midgut. Debra inhibition leads to increased ISC activity and tissue homeostasis loss, phenocopying defects observed in aging flies. These defects can be suppressed by depleting Ci, suggesting that increased Hedgehog (Hh) signaling contributes to ISC proliferation and tissue homeostasis loss. Consistently, Hh signaling activation causes the same defects, whereas depletion of Hh signaling suppresses these defects. Furthermore, the Hh ligand from multiple sources is involved in ISC proliferation and tissue homeostasis. Finally, we show that the JNK pathway acts downstream of Hh signaling to regulate ISC proliferation. Together, our results provide insights into the mechanisms of stem cell proliferation and tissue homeostasis control. PMID:24527387

  9. Minimal Incision Scar-Less Open Umbilical Hernia Repair in Adults – Technical Aspects and Short-Term Results

    PubMed Central

    Zachariah, Sanoop K.; Kolathur, Najeeb Mohamed; Balakrishnan, Mahesh; Parakkadath, Arun Joseph

    2014-01-01

    Background: There is no gold standard technique for umbilical hernia (UH) repair. Conventional open UH repair often produces an undesirable scar. Laparoscopic UH repair requires multiple incisions beyond the umbilicus, specialized equipments, and expensive tissue separating mesh. We describe our technique of open UH repair utilizing a small incision. The technique was derived from our experience with single incision laparoscopy. We report the technical details and short-term results. Methods: This is a retrospective analysis of the first 20 patients, who underwent minimal incision scar-less open UH repair, from June 2011 to February 2014. A single intra-umbilical curved incision was used to gain access to the hernia sac. Primary suture repair was performed for defects up to 2 cm. Larger defects were repaired using an onlay mesh. In patients with a BMI of 30 kg/m2 or greater, onlay mesh hernioplasty was performed irrespective of the defect size. Results: A total of 20 patients, 12 males and 8 females underwent the procedure. Mean age was 50 (range 29–82) years. Mean BMI was 26.27 (range 20.0–33.1) kg/m2. Average size of the incision was 1.96 range (1.5–2.5) cm. Mesh hernioplasty was done in nine patients. Eleven patients underwent primary suture repair alone. There were no postoperative complications associated with this technique. Average postoperative length of hospital stay was 3.9 (range 2–10) days. Mean follow-up was 29.94 months (2 weeks to 2.78 years). On follow-up there was no externally visible scar in any of the patients. There were no recurrences on final follow-up. Conclusion: This technique provides a similar cosmetic effect as obtained from single port laparoscopy. It is easy to perform, safe, offers good cosmesis, does not require incisions beyond the umbilicus, and cost effective, with encouraging results on short-term follow-up. Further research is needed to assess the true potential of the technique and the long-term results. PMID

  10. Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

    PubMed

    Dilley, Rodney J; Morrison, Wayne A

    2014-11-01

    Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. PMID:25449260

  11. Modeling the functional repair of nervous tissue in spinal cord injury

    NASA Astrophysics Data System (ADS)

    Mantila, Sara M.; Camp, Jon J.; Krych, Aaron J.; Robb, Richard A.

    2004-05-01

    Functional repair of traumatic spinal cord injury (SCI) is one of the most challenging goals in modern medicine. The annual incidence of SCI in the United States is approximately 11,000 new cases. The prevalence of people in the U.S. currently living with SCI is approximately 200,000. Exploring and understanding nerve regeneration in the central nervous system (CNS) is a critical first step in attempting to reverse the devastating consequences of SCI. At Mayo Clinic, a preliminary study of implants in the transected rat spinal cord model demonstrates potential for promoting axon regeneration. In collaborative research between neuroscientists and bioengineers, this procedure holds promise for solving two critical aspects of axon repair-providing a resorbable structural scaffold to direct focused axon repair, and delivery of relevant signaling molecules necessary to facilitate regeneration. In our preliminary study, regeneration in the rat's spinal cord was modeled in three dimensions utilizing an image processing software system developed in the Biomedical Imaging Resource at Mayo Clinic. Advanced methods for image registration, segmentation, and rendering were used. The raw images were collected at three different magnifications. After image processing the individual channels in the scaffold, axon bundles, and macrophages could be identified. Several axon bundles could be visualized and traced through the entire volume, suggesting axonal growth throughout the length of the scaffold. Such information could potentially allow researchers and physicians to better understand and improve the nerve regeneration process for individuals with SCI.

  12. Progress in Corneal Stromal Repair: From Tissue Grafts and Biomaterials to Modular Supramolecular Tissue-Like Assemblies.

    PubMed

    Kumar, Pramod; Pandit, Abhay; Zeugolis, Dimitrios I

    2016-07-01

    Corneal injuries and degenerative conditions have major socioeconomic consequences, given that in most cases, they result in blindness. In the quest of the ideal therapy, tissue grafts, biomaterials, and modular engineering approaches are under intense investigation. Herein, advancements and shortfalls are reviewed and future perspectives for these therapeutic strategies discussed. PMID:27028373

  13. Prognostic factors for a favorable outcome after varicocele repair in adolescents and adults

    PubMed Central

    Samplaski, Mary K; Jarvi, Keith A

    2016-01-01

    The effect of varicocele repair on male fertility remains controversial. It would be helpful to determined which men would benefit most from varicocele repair, and target repair efforts at those individuals. A detailed review of the literature on prognostic factors for varicocele repair was performed using the PubMed NLM database. We found that the best predictor of postvaricocelectomy semen parameters is the preoperative semen parameters. The greatest improvements in semen parameters were found in men with larger varicoceles. While there is controversy, higher testosterone, younger age and larger testis size, in some studies predict for improvements in semen parameters postvaricocelectomy. A nomogram has been developed to predict the postvaricocelectomy semen parameters based on the preoperative semen parameters, varicocele grade and the age of the man (www.fertilitytreatmentresults.com). Limited data consistently demonstrates the greatest improvements in DNA fragmentation rates in men with higher baseline DNA fragmentation rates. With respect to reproductive outcomes, higher baseline sperm density consistently predicts for natural pregnancy or assisted reproductive technology (ART) pregnancy rates. In addition, varicocele repair does seem to reduce the need for more invasive modalities of ART. In conclusion, we can now start to use specific parameters such as baseline semen quality, varicocele grade and patient age to predict post-repair semen quality and fertility potential following varicocelectomy. PMID:26732108

  14. Point-of-care instrument for monitoring tissue health during skin graft repair

    NASA Astrophysics Data System (ADS)

    Gurjar, R. S.; Seetamraju, M.; Zhang, J.; Feinberg, S. E.; Wolf, D. E.

    2011-06-01

    We have developed the necessary theoretical framework and the basic instrumental design parameters to enable mapping of subsurface blood dynamics and tissue oxygenation for patients undergoing skin graft procedures. This analysis forms the basis for developing a simple patch geometry, which can be used to map by diffuse optical techniques blood flow velocity and tissue oxygenation as a function of depth in subsurface tissue.skin graft, diffuse correlation analysis, oxygen saturation.

  15. Cytotoxicity of Cyanoacrylate-Based Tissue Adhesives and Short-Term Preclinical In Vivo Biocompatibility in Abdominal Hernia Repair

    PubMed Central

    Rodríguez, Marta; Pérez-Köhler, Bárbara; Kühnhardt, Andreé; Fernández-Gutiérrez, Mar; San Román, Julio; Bellón, Juan Manuel

    2016-01-01

    Background Cyanoacrylate(CA)-based tissue adhesives, although not widely used, are a feasible option to fix a mesh during abdominal hernia repair, due to its fast action and great bond strength. Their main disadvantage, toxicity, can be mitigated by increasing the length of their alkyl chain. The objective was to assess the in vitro cytotoxicity and in vivo biocompatibility in hernia repair of CAs currently used in clinical practice (Glubran(n-butyl) and Ifabond(n-hexyl)) and a longer-chain CA (OCA(n-octyl)), that has never been used in the medical field. Methods Formaldehyde release and cytotoxicity of unpolymerized(UCAs) and polymerized CAs(PCAs) were evaluated by macroscopic visual assessment, flow cytometry and Alamar Blue assays. In the preclinical evaluation, partial defects were created in the rabbit abdominal wall and repaired by fixing polypropylene prostheses using the CAs. At 14 days post-surgery, animals were euthanized for morphology, macrophage response and cell damage analyses. Results Formaldehyde release was lower as the molecular weight of the monomer increased. The longest side-chain CA(OCA) showed the highest cytotoxicity in the UCA condition. However, after polymerization, was the one that showed better behavior on most occasions. In vivo, all CAs promoted optimal mesh fixation without displacements or detachments. Seroma was evident with the use of Glubran, (four of six animals: 4/6) and Ifabond (2/6), but it was reduced with the use of OCA (1/6). Significantly greater macrophage responses were observed in groups where Glubran and Ifabond were used vs. sutures and OCA. TUNEL-positive cells were significantly higher in the Glubran and OCA groups vs. the suture group. Conclusions Although mild formaldehyde release occurred, OCA was the most cytotoxic during polymerization but the least once cured. The CAs promoted proper mesh fixation and have potential to replace traditional suturing techniques in hernia repair; the CAs exhibited good tissue

  16. Tissue regeneration and repair of goat segmental femur defect with bioactive triphasic ceramic-coated hydroxyapatite scaffold.

    PubMed

    Nair, Manitha B; Varma, H K; Menon, K V; Shenoy, Sachin J; John, Annie

    2009-12-01

    Bone tissue engineering which is a developing and challenging field of science, is expected to enhance the regeneration and repair of bone lost from injury or disease and ultimately to gain its aesthetic contour. The objective of this study was to fabricate a tissue-engineered construct in vitro using a triphasic ceramic-coated hydroxypatite (HASi) in combination with stem cells and to investigate its potential in healing segmental defect in goat model. To accomplish this attempt, mesenchymal stem cells isolated from goat bone marrow were seeded onto HASi scaffolds and induced to differentiate into the osteogenic lineage in vitro. Scanning electron microscopy and light microscopy revealed adhesion and spread-out cells, which eventually formed a cell-sheet like canopy over the scaffold. Cells migrated and distributed themselves within the internal voids of the porous ceramic. Concurrently, the neo-osteogenesis of the tissue-engineered construct was validated in vivo in comparison with bare HASi (without cells) in goat femoral diaphyseal segmental defect (2 cm) at 4 months postimplantation through radiography, computed tomography, histology, histomorphometry, scanning electron microscopy and inductively coupled plasma spectrometry. Good osteointegration and osteoconduction was observed in bare and tissue-engineered HASi. The performance of tissue-engineered HASi was better and faster which was evident by the lamellar bone organization of newly formed bone throughout the defect together with the degradation of the material. On the contrary with bare HASi, immature woven bony bridges still intermingled with scattered small remnants of the material was observed in the mid region of the defect at 4 months. Encouraging results from this preclinical study has proved the capability of the tissue-engineered HASi as a promising candidate for the reconstruction of similar bony defects in humans. PMID:19065569

  17. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches

    PubMed Central

    Pekovic, Vanja; Hutchison, Christopher J

    2008-01-01

    Adult stem cells have been identified in most mammalian tissues of the adult body and are known to support the continuous repair and regeneration of tissues. A generalized decline in tissue regenerative responses associated with age is believed to result from a depletion and/or a loss of function of adult stem cells, which itself may be a driving cause of many age-related disease pathologies. Here we review the striking similarities between tissue phenotypes seen in many degenerative conditions associated with old age and those reported in age-related nuclear envelope disorders caused by mutations in the LMNA gene. The concept is beginning to emerge that nuclear filament proteins, A-type lamins, may act as signalling receptors in the nucleus required for receiving and/or transducing upstream cytosolic signals in a number of pathways central to adult stem cell maintenance as well as adaptive responses to stress. We propose that during ageing and in diseases caused by lamin A mutations, dysfunction of the A-type lamin stress-resistant signalling network in adult stem cells, their progenitors and/or stem cell niches leads to a loss of protection against growth-related stress. This in turn triggers an inappropriate activation or a complete failure of self-renewal pathways with the consequent initiation of stress-induced senescence. As such, A-type lamins should be regarded as intrinsic modulators of ageing within adult stem cells and their niches that are essential for survival to old age. PMID:18638067

  18. Multi-stage resection and repair for the treatment of adult giant sacrococcygeal teratoma: A case report and literature review

    PubMed Central

    SHENG, QIN-SONG; XU, XIANG-MING; CHENG, XIAO-BIN; WANG, WEI-BING; CHEN, WEN-BIN; LIN, JIAN-JIANG; XU, JIA-HE

    2015-01-01

    Sacrococcygeal teratoma (SCT) is a sacrococcygeal neoplasm derived from more than one primitive germ layer and is only occasionally encountered in adults. The primary treatment for all primary SCTs is surgical excision. The present study reports the case of a giant SCT in a middle-aged female with a history lasting >3 decades. Multi-staged surgical treatment was performed, including ileostomy plus tumor excision, four debridement plus flap repair procedures, and closure of the ileostomy. Follow-up showed improved quality of life without evidence of local recurrence after resection. The study also presents a brief overview of the relevant literature. To the best of our knowledge, this is the first report of multi-staged surgical treatment for giant SCT in an adult patient. PMID:26171044

  19. Quantitative assessment of systolic left ventricular function with speckle-tracking echocardiography in adult patients with repaired aortic coarctation.

    PubMed

    Menting, Myrthe E; van Grootel, Roderick W J; van den Bosch, Annemien E; Eindhoven, Jannet A; McGhie, Jackie S; Cuypers, Judith A A E; Witsenburg, Maarten; Helbing, Willem A; Roos-Hesselink, Jolien W

    2016-05-01

    Despite successful aortic coarctation (CoA) repair, systemic hypertension often recurs which may influence left ventricular (LV) function. We aimed to detect early LV dysfunction using LV global longitudinal strain (GLS) in adults with repaired CoA, and to identify associations with patient and echocardiographic characteristics. In this cross-sectional study, patients with repaired CoA and healthy controls were recruited prospectively. All subjects underwent echocardiography, ECG and blood sampling within 1 day. With speckle-tracking echocardiography, we assessed LV GLS on the apical four-, three- and two-chamber views. We included 150 subjects: 75 patients (57 % male, age 33.4 ± 12.8 years, age at repair 2.5 [IQR: 0.1-11.1] years) and 75 healthy controls of similar sex and age. LV GLS was lower in patients than in controls (-17.1 ± 2.3 vs. -20.2 ± 1.6 %, P < 0.001). Eighty percent of the patients had a normal LV ejection fraction, but GLS was still lower than in controls (P < 0.001). In patients, GLS correlated with systolic and diastolic blood pressure (r = 0.32, P = 0.009; r = 0.31, P = 0.009), QRS duration (r = 0.34, P = 0.005), left atrial dimension (r = 0.27, P = 0.029), LV mass (r = 0.30, P = 0.014) and LV ejection fraction (r = -0.48, P < 0.001). Patients with either associated cardiac lesions, multiple cardiac interventions or aortic valve replacement had lower GLS than patients without. Although the majority of adults with repaired CoA seem to have a normal systolic LV function, LV GLS was decreased. Higher blood pressure, associated cardiac lesions, and larger left atrial dimension are related with lower GLS. Therefore, LV GLS may be used as objective criterion for early detection of ventricular dysfunction. PMID:26780661

  20. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    PubMed Central

    Soares, Milena B. P.; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M.; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ∼30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease causal agent, ie, the T. cruzi, are described herein. Bone marrow cells injected intravenously into chronic chagasic mice migrated to the heart and caused a significant reduction in the inflammatory infiltrates and in the interstitial fibrosis characteristics of chronic chagasic cardiomyopathy. The beneficial effects were observed up to 6 months after bone marrow cell transplantation. A massive apoptosis of myocardial inflammatory cells was observed after the therapy with bone marrow cells. Transplanted bone marrow cells obtained from chagasic mice and from normal mice had similar effects in terms of mediating chagasic heart repair. These results show that bone marrow cell transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy. PMID:14742250

  1. Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs

    PubMed Central

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Cho, Yong-Bum; Park, Jong-Seong; Jeong, Han-Seong

    2016-01-01

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks’ balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs. PMID:27482231

  2. Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs.

    PubMed

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Cho, Yong-Bum; Park, Jong-Seong; Jeong, Han-Seong

    2016-06-01

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks' balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs. PMID:27482231

  3. Signaling through ERK1/2 controls myelin thickness during myelin repair in the adult central nervous system.

    PubMed

    Fyffe-Maricich, Sharyl L; Schott, Alexandra; Karl, Molly; Krasno, Janet; Miller, Robert H

    2013-11-20

    Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin. PMID:24259565

  4. A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

    PubMed Central

    Pei, Ming; Li, Jingting; McConda, David B.; Wen, Sijin; Clovis, Nina B.; Danley, Suzanne S.

    2015-01-01

    Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly (lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici’s collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats. PMID:25940459

  5. The molecular nature of very small embryonic-like stem cells in adult tissues.

    PubMed

    Kim, YongHwan; Jeong, Jaeho; Kang, Hyunsook; Lim, Jisun; Heo, Jinbeom; Ratajczak, Janina; Ratajczak, Mariusz Z; Shin, Dong-Myung

    2014-11-01

    Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (∼3-6 μm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells. PMID:25473442

  6. The Molecular Nature of Very Small Embryonic-Like Stem Cells in Adult Tissues

    PubMed Central

    Kim, YongHwan; Jeong, Jaeho; Kang, Hyunsook; Lim, Jisun; Heo, Jinbeom; Ratajczak, Janina; Ratajczak, Mariusz Z.; Shin, Dong-Myung

    2014-01-01

    Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4+ SSEA-1+Sca-1+Lin−CD45− very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (∼3–6 μm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells. PMID:25473442

  7. Facial soft tissue thickness in individuals with different occlusion patterns in adult Turkish subjects.

    PubMed

    Kurkcuoglu, Ayla; Pelin, Can; Ozener, Bariş; Zagyapan, Ragiba; Sahinoglu, Zahira; Yazici, Ayse Canan

    2011-08-01

    Knowledge of variation in facial soft tissue thickness is important for forensic anthropologists, dentists, and plastic surgeons. Forensic anthropologists use such information as a guide in facial reconstruction and superimposition methods. The purpose of this study was to measure facial tissue thicknesses of adult males and females of Turkish origin across different types of occlusion, and to compare the results with each other and with values obtained for other populations. The study was conducted on 200 healthy individuals. The analysis of facial tissue thickness included 20 landmarks (10 dentoskeletal and 10 soft tissue) and 10 linear variables. Sex-based variation in facial tissue thickness was noted. The highest soft tissue thickness values were observed in the group with Class III occlusion type at Sn-A point for both the females (16.9, SD=2.4) and the males (17.8, SD=3.3). In the Class I group, the highest tissue depth was observed at Sn-A point (15.3, SD=2.1) in females, and at Li-Id point (17.1, SD=1.9) in males. In the Class II group, contrary to the findings for Class I, the highest soft tissue depth was at Li-Id point (16.0, SD=1.4) in females, and at Sn-A point (18.1, SD=2.6) in males. In conclusion, facial tissue thickness varied in adults depending on the sex and on the type of occlusion. PMID:21741647

  8. Low power laser irradiation stimulates cell proliferation via proliferating cell nuclear antigen and Ki-67 expression during tissue repair

    NASA Astrophysics Data System (ADS)

    Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Mahato, Krishna Kishore

    2015-03-01

    Low power laser irradiation (LPLI) is becoming an increasingly popular and fast growing therapeutic modality in dermatology to treat various ailments without any reported side effects. In the present study an attempt was made to investigate the proliferative potential of red laser light during tissue repair in Swiss albino mice. To this end, full thickness excisional wounds of diameter 15 mm created on mice were exposed to single dose of Helium-Neon laser (632.8 nm; 7 mW; 4.02 mWcm-2; Linear polarization) at 2 Jcm-2 and 10 Jcm-2 along with un-illuminated controls. The granulation tissues from all the respective experimental groups were harvested on day 10 post-wounding following euthanization. Subsequently, tissue regeneration potential of these laser doses under study were evaluated by monitoring proliferating cell nuclear antigen and Ki-67 following the laser treatment and comparing it with the un-illuminated controls. The percentages of Ki-67 or PCNA positive cells were determined by counting positive nuclei (Ki-67/PCNA) and total nuclei in five random fields per tissue sections. Animal wounds treated with single exposure of the 2 Jcm-2 indicated significant elevation in PCNA (P<0.01) and Ki-67 (P<0.05 compared to un-illuminated control and P<0.01 compared to 10 Jcm-2) expression as compared to other tested experimental groups as evidenced by the microscopy results in the study. In summary, the findings of the present study have clearly demonstrated the regulation of cell proliferation by LPLI via PCNA and Ki-67 expression during tissue regeneration.

  9. Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Allyl isothiocyanate (AITC) is a dietary component with potentially important anti-cancer effects, though much of the information about AITC and cancer processes has been obtained from cell studies. To investigate the effect of AITC on DNA integrity and repair in vivo, a human feeding study was con...

  10. Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair

    PubMed Central

    Barreiro, Olga; Cibrian, Danay; Clemente, Cristina; Alvarez, David; Moreno, Vanessa; Valiente, Íñigo; Bernad, Antonio; Vestweber, Dietmar; Arroyo, Alicia G; Martín, Pilar; von Andrian, Ulrich H; Sánchez Madrid, Francisco

    2016-01-01

    Heterogeneity and functional specialization among skin-resident macrophages are incompletely understood. In this study, we describe a novel subset of murine dermal perivascular macrophages that extend protrusions across the endothelial junctions in steady-state and capture blood-borne macromolecules. Unlike other skin-resident macrophages that are reconstituted by bone marrow-derived progenitors after a genotoxic insult, these cells are replenished by an extramedullary radio-resistant and UV-sensitive Bmi1+ progenitor. Furthermore, they possess a distinctive anti-inflammatory transcriptional profile, which cannot be polarized under inflammatory conditions, and are involved in repair and remodeling functions for which other skin-resident macrophages appear dispensable. Based on all their properties, we define these macrophages as Skin Transendothelial Radio-resistant Anti-inflammatory Macrophages (STREAM) and postulate that their preservation is important for skin homeostasis. DOI: http://dx.doi.org/10.7554/eLife.15251.001 PMID:27304075

  11. Mechanical Properties of Mesh Materials Used for Hernia Repair and Soft Tissue Augmentation

    PubMed Central

    Pott, Peter P.; Schwarz, Markus L. R.; Gundling, Ralf; Nowak, Kai; Hohenberger, Peter; Roessner, Eric D.

    2012-01-01

    Background Hernia repair is the most common surgical procedure in the world. Augmentation with synthetic meshes has gained importance in recent decades. Most of the published work about hernia meshes focuses on the surgical technique, outcome in terms of mortality and morbidity and the recurrence rate. Appropriate biomechanical and engineering terminology is frequently absent. Meshes are under continuous development but there is little knowledge in the public domain about their mechanical properties. In the presented experimental study we investigated the mechanical properties of several widely available meshes according to German Industrial Standards (DIN ISO). Methodology/Principal Findings Six different meshes were assessed considering longitudinal and transverse direction in a uni-axial tensile test. Based on the force/displacement curve, the maximum force, breaking strain, and stiffness were computed. According to the maximum force the values were assigned to the groups weak and strong to determine a base for comparison. We discovered differences in the maximum force (11.1±6.4 to 100.9±9.4 N/cm), stiffness (0.3±0.1 to 4.6±0.5 N/mm), and breaking strain (150±6% to 340±20%) considering the direction of tension. Conclusions/Significance The measured stiffness and breaking strength vary widely among available mesh materials for hernia repair, and most of the materials show significant anisotropy in their mechanical behavior. Considering the forces present in the abdominal wall, our results suggest that some meshes should be implanted in an appropriate orientation, and that information regarding the directionality of their mechanical properties should be provided by the manufacturers. PMID:23071685

  12. Analysis of RF exposure in the head tissues of children and adults

    NASA Astrophysics Data System (ADS)

    Wiart, J.; Hadjem, A.; Wong, M. F.; Bloch, I.

    2008-07-01

    This paper analyzes the radio frequencies (RF) exposure in the head tissues of children using a cellular handset or RF sources (a dipole and a generic handset) at 900, 1800, 2100 and 2400 MHz. Based on magnetic resonance imaging, child head models have been developed. The maximum specific absorption rate (SAR) over 10 g in the head has been analyzed in seven child and six adult heterogeneous head models. The influence of the variability in the same age class is carried out using models based on a morphing technique. The SAR over 1 g in specific tissues has also been assessed in the different types of child and adult head models. Comparisons are performed but nevertheless need to be confirmed since they have been derived from data sets of limited size. The simulations that have been performed show that the differences between the maximum SAR over 10 g estimated in the head models of the adults and the ones of the children are small compared to the standard deviations. But they indicate that the maximum SAR in 1 g of peripheral brain tissues of the child models aged between 5 and 8 years is about two times higher than in adult models. This difference is not observed for the child models of children above 8 years old: the maximum SAR in 1 g of peripheral brain tissues is about the same as the one in adult models. Such differences can be explained by the lower thicknesses of pinna, skin and skull of the younger child models.

  13. Response of endothelial cells and pericytes to hypoxia and erythropoietin in a co-culture assay dedicated to soft tissue repair.

    PubMed

    Schneider, Gerrit; Bubel, Monika; Pohlemann, Tim; Oberringer, Martin

    2015-09-01

    The increasing mean life expectancy of the citizens of the western world countries leads to an increase of the age-related diseases, among them soft tissue defects exhibiting inadequate healing. In order to develop new therapeutic strategies to support disturbed soft tissue repair, there is a strong need of sophisticated in vitro assays. A new assay combining scratch wounding with co-cultures of primary human microvascular endothelial cells (HDMEC) and pericytes (HPC) focuses on basic characteristics of cell interaction against the background of soft tissue repair. The cell parameters proliferation, migration and differentiation, and the release of monocyte chemoattractant protein-1 (MCP-1) were analysed in response to hypoxia (pO2 < 5 mmHg) and to erythropoietin (EPO; 50 IU/ml), a glycoprotein hormone having shown promising effects in soft tissue repair. As basic characteristics of the assay, direct cell contact in co-culture led to a weakened proliferation of both cell types, an increase of the percentage of myofibroblast-like pericytes and to a higher release of MCP-1. Hypoxia caused a proliferation decrease of HPC in co-culture, which was slightly attenuated by EPO. Hypoxia also reduced the MCP-1 release of co-cultured cells, when EPO had been added. In addition, EPO had a rather positive effect on HPC migration under hypoxia. These in vitro results allow new insights into the interaction of pericytes with endothelial cells in the context of soft tissue repair. PMID:26026617

  14. Alpha-tubulin enhanced renal tubular cell proliferation and tissue repair but reduced cell death and cell-crystal adhesion.

    PubMed

    Manissorn, Juthatip; Khamchun, Supaporn; Vinaiphat, Arada; Thongboonkerd, Visith

    2016-01-01

    Adhesion of calcium oxalate (CaOx) crystals on renal tubular epithelial cells is a critical event for kidney stone disease that triggers many cascades of cellular response. Our previous expression proteomics study identified several altered proteins in MDCK renal tubular cells induced by CaOx crystals. However, functional significance of those changes had not been investigated. The present study thus aimed to define functional roles of such proteome data. Global protein network analysis using STRING software revealed α-tubulin, which was decreased, as one of central nodes of protein-protein interactions. Overexpression of α-tubulin (pcDNA6.2-TUBA1A) was then performed and its efficacy was confirmed. pcDNA6.2-TUBA1A could maintain levels of α-tubulin and its direct interacting partner, vimentin, after crystal exposure. Also, pcDNA6.2-TUBA1A successfully reduced cell death to almost the basal level and increased cell proliferation after crystal exposure. Additionally, tissue repair capacity was improved in pcDNA6.2-TUBA1A cells. Moreover, cell-crystal adhesion was reduced by pcDNA6.2-TUBA1A. Finally, levels of potential crystal receptors (HSP90, HSP70, and α-enolase) on apical membrane were dramatically reduced to basal levels by pcDNA6.2-TUBA1A. These findings implicate that α-tubulin has protective roles in kidney stone disease by preventing cell death and cell-crystal adhesion, but on the other hand, enhancing cell proliferation and tissue repair function. PMID:27363348

  15. Photographic-Based Optical Evaluation of Tissues and Biomaterials Used for Corneal Surface Repair: A New Easy-Applied Method

    PubMed Central

    Gonzalez-Andrades, Miguel; Cardona, Juan de la Cruz; Ionescu, Ana Maria; Mosse, Charles A.; Brown, Robert A.

    2015-01-01

    Purpose Tissues and biomaterials used for corneal surface repair require fulfilling specific optical standards prior to implantation in the patient. However, there is not a feasible evaluation method to be applied in clinical or Good Manufacturing Practice settings. In this study, we describe and assess an innovative easy-applied photographic-based method (PBM) for measuring functional optical blurring and transparency in corneal surface grafts. Methods Plastic compressed collagen scaffolds (PCCS) and multilayered amniotic membranes (AM) samples were optically and histologically evaluated. Transparency and image blurring measures were obtained by PBM, analyzing photographic images of a standardized band pattern taken through the samples. These measures were compared and correlated to those obtained applying the Inverse Adding-Doubling (IAD) technique, which is the gold standard method. Results All the samples used for optical evaluation by PBM or IAD were histological suitable. PCCS samples presented transmittance values higher than 60%, values that increased with increasing wavelength as determined by IAD. The PBM indicated that PCCS had a transparency ratio (TR) value of 80.3±2.8%, with a blurring index (BI) of 50.6±4.2%. TR and BI obtained from the PBM showed a high correlation (ρ>|0.6|) with the diffuse transmittance and the diffuse reflectance, both determined using the IAD (p<0.005). The AM optical properties showed that there was a largely linear relationship between the blurring and the number of amnion layers, with more layers producing greater blurring. Conclusions This innovative proposed method represents an easy-applied technique for evaluating transparency and blurriness of tissues and biomaterials used for corneal surface repair. PMID:26566050

  16. Alpha-tubulin enhanced renal tubular cell proliferation and tissue repair but reduced cell death and cell-crystal adhesion

    PubMed Central

    Manissorn, Juthatip; Khamchun, Supaporn; Vinaiphat, Arada; Thongboonkerd, Visith

    2016-01-01

    Adhesion of calcium oxalate (CaOx) crystals on renal tubular epithelial cells is a critical event for kidney stone disease that triggers many cascades of cellular response. Our previous expression proteomics study identified several altered proteins in MDCK renal tubular cells induced by CaOx crystals. However, functional significance of those changes had not been investigated. The present study thus aimed to define functional roles of such proteome data. Global protein network analysis using STRING software revealed α-tubulin, which was decreased, as one of central nodes of protein-protein interactions. Overexpression of α-tubulin (pcDNA6.2-TUBA1A) was then performed and its efficacy was confirmed. pcDNA6.2-TUBA1A could maintain levels of α-tubulin and its direct interacting partner, vimentin, after crystal exposure. Also, pcDNA6.2-TUBA1A successfully reduced cell death to almost the basal level and increased cell proliferation after crystal exposure. Additionally, tissue repair capacity was improved in pcDNA6.2-TUBA1A cells. Moreover, cell-crystal adhesion was reduced by pcDNA6.2-TUBA1A. Finally, levels of potential crystal receptors (HSP90, HSP70, and α-enolase) on apical membrane were dramatically reduced to basal levels by pcDNA6.2-TUBA1A. These findings implicate that α-tubulin has protective roles in kidney stone disease by preventing cell death and cell-crystal adhesion, but on the other hand, enhancing cell proliferation and tissue repair function. PMID:27363348

  17. Minced Tissue in Compressed Collagen: A Cell-containing Biotransplant for Single-staged Reconstructive Repair.

    PubMed

    Chamorro, Clara I; Zeiai, Said; Reinfeldt Engberg, Gisela; Fossum, Magdalena

    2016-01-01

    Conventional techniques for cell expansion and transplantation of autologous cells for tissue engineering purposes can take place in specially equipped human cell culture facilities. These methods include isolation of cells in single cell suspension and several laborious and time-consuming events before transplantation back to the patient. Previous studies suggest that the body itself could be used as a bioreactor for cell expansion and regeneration of tissue in order to minimize ex vivo manipulations of tissues and cells before transplanting to the patient. The aim of this study was to demonstrate a method for tissue harvesting, isolation of continuous epithelium, mincing of the epithelium into small pieces and incorporating them into a three-layered biomaterial. The three-layered biomaterial then served as a delivery vehicle, to allow surgical handling, exchange of nutrition across the transplant, and a controlled degradation. The biomaterial consisted of two outer layers of collagen and a core of a mechanically stable and slowly degradable polymer. The minced epithelium was incorporated into one of the collagen layers before transplantation. By mincing the epithelial tissue into small pieces, the pieces could be spread and thereby the propagation of cells was stimulated. After the initial take of the transplants, cell expansion and reorganization would take place and extracellular matrix mature to allow ingrowth of capillaries and nerves and further maturation of the extracellular matrix. The technique minimizes ex vivo manipulations and allow cell harvesting, preparation of autograft, and transplantation to the patient as a simple one-stage intervention. In the future, tissue expansion could be initiated around a 3D mold inside the body itself, according to the specific needs of the patient. Additionally, the technique could be performed in an ordinary surgical setting without the need for sophisticated cell culturing facilities. PMID:26967119

  18. Adipose tissue gene expression and metabolic health of obese adults.

    PubMed

    Das, S K; Ma, L; Sharma, N K

    2015-05-01

    Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardiometabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ⩾40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (group 1) and one metabolically unhealthy (group 2). Subjects in group 2 showed significantly higher total cholesterol (P=0.005), low-density lipoprotein cholesterol (P=0.006), 2-h insulin during oral glucose tolerance test (P=0.015) and lower insulin sensitivity (SI, P=0.029) compared with group 1. We identified significant upregulation of 141 genes (for example, MMP9 and SPP1) and downregulation of 17 genes (for example, NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (P=2.81 × 10(-11)-3.74 × 10(-02)) and pathways involved in immune and inflammatory response (P=8.32 × 10(-5)-0.04). Two downregulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects. PMID:25520251

  19. The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.

    PubMed

    Pahnke, Aric; Conant, Genna; Huyer, Locke Davenport; Zhao, Yimu; Feric, Nicole; Radisic, Milica

    2016-05-01

    Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models. PMID:26626076

  20. Evaluation of skeletal tissue repair, part 1: assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model.

    PubMed

    Smith, E L; Kanczler, J M; Gothard, D; Roberts, C A; Wells, J A; White, L J; Qutachi, O; Sawkins, M J; Peto, H; Rashidi, H; Rojo, L; Stevens, M M; El Haj, A J; Rose, F R A J; Shakesheff, K M; Oreffo, R O C

    2014-10-01

    Current clinical treatments for skeletal conditions resulting in large-scale bone loss include autograft or allograft, both of which have limited effectiveness. In seeking to address bone regeneration, several tissue engineering strategies have come to the fore, including the development of growth factor releasing technologies and appropriate animal models to evaluate repair. Ex vivo models represent a promising alternative to simple in vitro systems or complex, ethically challenging in vivo models. We have developed an ex vivo culture system of whole embryonic chick femora, adapted in this study as a critical size defect model to investigate the effects of novel bone extracellular matrix (bECM) hydrogel scaffolds containing spatio-temporal growth factor-releasing microparticles and skeletal stem cells on bone regeneration, to develop a viable alternative treatment for skeletal degeneration. Alginate/bECM hydrogels combined with poly (d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PDLLGA) microparticles releasing VEGF, TGF-β3 or BMP-2 were placed, with human adult Stro-1+ bone marrow stromal cells, into 2mm central segmental defects in embryonic chick femurs. Alginate/bECM hydrogels loaded with HSA/VEGF or HSA/TGF-β3 demonstrated a cartilage-like phenotype, with minimal collagen I deposition, comparable to HSA-only control hydrogels. The addition of BMP-2 releasing microparticles resulted in enhanced structured bone matrix formation, evidenced by increased Sirius red-stained matrix and collagen expression within hydrogels. This study demonstrates delivery of bioactive growth factors from a novel alginate/bECM hydrogel to augment skeletal tissue formation and the use of an organotypic chick femur defect culture system as a high-throughput test model for scaffold/cell/growth factor therapies for regenerative medicine. PMID:24937137

  1. Innate immune system and tissue regeneration in Planarians: An area ripe for exploration

    PubMed Central

    Peiris, T. Harshani; Hoyer, Katrina K.; Oviedo, Néstor J.

    2014-01-01

    The immune system has been implicated as an important modulator of tissue regeneration. However, the mechanisms driving injury-induced immune response and tissue repair remain poorly understood. For over 200 years, planarians have been a classical model for studies on tissue regeneration, but the planarian immune system and its potential role in repair is largely unknown. We found through comparative genomic analysis and data mining that planarians contain many potential homologs of the innate immune system that are activated during injury and repair of adult tissues. These findings support the notion that the relationship between adult tissue repair and the immune system is an ancient feature of basal Bilateria. Further analysis of the planarian immune system during regeneration could potentially add to our understanding of how the innate immune system and inflammatory responses interplay with regenerative signals to induce scar-less tissue repair in the context of the adult organism. PMID:25082737

  2. Stromal vascular progenitors in adult human adipose tissue

    PubMed Central

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Pfeifer, Melanie E.; Meyer, E. Michael; Péault, Bruno; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    Background The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Methods Immunohistostaining of intact adipose tissue was used to identify 3 markers (CD31, CD34, CD146) which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90, CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture and tested for adipogenesis. Results The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/α-SMA+/CD90±/CD34−/CD31−; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146−/α-SMA−/CD90+/CD34+/CD31−. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), while small vessel endothelium was CD31+/CD34−/CD90− (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31− pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared to unsorted expanded SVF cells. Conclusions In adipose tissue perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34− pericytes, and the outermost of CD146−/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD

  3. In vitro and in vivo evaluation of orthopedic interface repair using a tissue scaffold with a continuous hard tissue-soft tissue transition

    PubMed Central

    2013-01-01

    Tendon tears produce pain and decrease joint stability; each year, over 1.1 million rotator cuff tendon surgical procedures are performed worldwide. However, surgical success is highly variable, and the inability of the procedure to drive the regeneration of the normal tendon-bone interface has been identified as a key factor in surgical failure. This study focuses on the development, in vitro evaluation, and in vivo assessment of a tissue scaffold derived from bovine cancellous bone with the potential to direct regeneration of a bone-soft tissue interface. The scaffold is a highly porous scaffold with a continuous hard tissue-soft tissue transition that facilitates load transfer across the interface and contains all of the extracellular matrix components of the orthopedic interface. This study demonstrated the in vitro characterization of the mechanical properties and successful in vivo assessment using an ovine model. PMID:23782505

  4. Use of a biological reactor and platelet-rich plasma for the construction of tissue-engineered bone to repair articular cartilage defects

    PubMed Central

    Li, Huibo; Sun, Shui; Liu, Haili; Chen, Hua; Rong, Xin; Lou, Jigang; Yang, Yunbei; Yang, Yi; Liu, Hao

    2016-01-01

    Articular cartilage defects are a major clinical burden worldwide. Current methods to repair bone defects include bone autografts, allografts and external fixation. In recent years, the repair of bone defects by tissue engineering has emerged as a promising approach. The present study aimed to assess a novel method using a biological reactor with platelet-rich plasma to construct tissue-engineered bone. Beagle bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into osteoblasts and chondroblasts using platelet-rich plasma and tricalcium phosphate scaffolds cultured in a bioreactor for 3 weeks. The cell scaffold composites were examined by scanning electron microscopy (SEM) and implanted into beagles with articular cartilage defects. The expression of osteogenic markers, alkaline phosphatase and bone γ-carboxyglutamate protein (BGLAP) were assessed using polymerase chain reaction after 3 months. Articular cartilage specimens were observed histologically. Adhesion and distribution of BMSCs on the β-tricalcium phosphate (β-TCP) scaffold were confirmed by SEM. Histological examination revealed that in vivo bone defects were largely repaired 12 weeks following implantation. The expression levels of alkaline phosphatase (ALP) and BGLAP in the experimental groups were significantly elevated compared with the negative controls. BMSCs may be optimum seed cells for tissue engineering in bone repair. Platelet-rich plasma (PRP) provides a rich source of cytokines to promote BMSC function. The β-TCP scaffold is advantageous for tissue engineering due to its biocompatibility and 3D structure that promotes cell adhesion, growth and differentiation. The tissue-engineered bone was constructed in a bioreactor using BMSCs, β-TCP scaffolds and PRP and displayed appropriate morphology and biological function. The present study provides an efficient method for the generation of tissue-engineered bone for cartilage repair, compared with previously used

  5. Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair

    PubMed Central

    Bhangra, Kulraj Singh; Busuttil, Francesca

    2016-01-01

    Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application. PMID:27212954

  6. Design of injectable organic-inorganic hybrid for bone tissue repair.

    PubMed

    Dessì, Mariagemiliana; Raucci, Maria Grazia; Zeppetelli, Stefania; Ambrosio, Luigi

    2012-08-01

    Injectable bone substitutes are rapidly gained success in tissue engineering applications for their less invasive surgical aspect. Here, the design and the characterization of a novel degradable paste of PCL reinforced with nanocrystals of hydroxyapatite have been presented aiming to mimic natural tissue. Nanohydroxyapatite has been successfully synthesized via sol-gel technique. Dynamic and steady state viscoelastic properties of the solutions and paste were investigated to control the kinetic of phase transition. Correspondingly, the morphology and composition were characterized via TEM, EDAX, and thermal analysis. Injection test underlines the completely ability of the paste of being injected without altering its features. Preliminary biological study showed that the composite paste is not cytotoxic. The synergistic rheological and biological properties, combined with the positive effect of chemical synthesis method indicate that the composite paste is very suitable as local bone substitute in low-load areas. PMID:22581691

  7. Induction of endometrial mesenchymal stem cells into tissue-forming cells suitable for fascial repair.

    PubMed

    Su, Kai; Edwards, Sharon L; Tan, Ker S; White, Jacinta F; Kandel, Shital; Ramshaw, John A M; Gargett, Caroline E; Werkmeister, Jerome A

    2014-12-01

    Pelvic organ prolapse is a major hidden burden affecting almost one in four women. It is treated by reconstructive surgery, often augmented with synthetic mesh. To overcome the growing concerns of using current synthetic meshes coupled with the high risk of reoperation, a tissue engineering strategy has been developed, adopting a novel source of mesenchymal stem cells. These cells are derived from the highly regenerative endometrial lining of the uterus (eMSCs) and will be delivered in vivo using a new gelatin-coated polyamide scaffold. In this study, gelatin properties were optimized by altering the gelatin concentration and extent of crosslinking to produce the desired gelation and degradation rate in culture. Following cell seeding of uncoated polyamide (PA) and gelatin-coated meshes (PA+G), the growth rate of eMSCs on the PA+G scaffolds was more than that on the PA alone, without compromising cell shape. eMSCs cultured on the PA+G scaffold retained their phenotype, as demonstrated by W5C5/SUSD2 (eMSC-specific marker) immunocytochemistry. Additionally, eMSCs were induced to differentiate into smooth muscle cells (SMC), as shown by immunofluorescence for smooth muscle protein 22 and smooth muscle myosin heavy chain. eMSCs also differentiated into fibroblast-like cells when treated with connective tissue growth factor with enhanced detection of Tenascin-C and collagen type I as well as new tissue formation, as seen by Masson's trichrome. In summary, it was demonstrated that the PA+G scaffold is an appropriate platform for eMSC delivery, proliferation and differentiation into SMC and fibroblasts, with good biocompatibility and the capacity to regenerate neo-tissue. PMID:25194931

  8. A bioactive hybrid three-dimensional tissue-engineering construct for cartilage repair.

    PubMed

    Ainola, Mari; Tomaszewski, Waclaw; Ostrowska, Barbara; Wesolowska, Ewa; Wagner, H Daniel; Swieszkowski, Wojciech; Sillat, Tarvo; Peltola, Emilia; Konttinen, Yrjö T

    2016-01-01

    The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication. The polycaprolactone support was coated with a chitosan/polyethylene oxide nanofibre sheet produced by electrospinning. Transforming growth factor-β3-induced chondrogenesis was followed using the following markers: sex determining region Y/-box 9, runt-related transcription factor 2 and collagen II and X in quantitative real-time polymerase chain reaction, histology and immunostaining. A polycaprolactone-grate and an optimized chitosan/polyethylene oxide nanofibre sheet supported cellular aggregation, chondrogenesis and matrix formation. In tissue engineering constructs, the sheets were seeded first with mesenchymal stem cells and then piled up according to the lasagne principle. The advantages of such a construct are (1) the cells do not need to migrate to the tissue engineering construct and therefore pore size and interconnectivity problems are omitted and (2) the cell-tight nanofibre sheet and collagen-fibre network mimic a cell culture platform for mesenchymal stem cells/chondrocytes (preventing escape) and hinders in-growth of fibroblasts and fibrous scarring (preventing capture). This allows time for the slowly progressing, multiphase true cartilage regeneration. PMID:26341661

  9. A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair.

    PubMed

    Wang, Jing; Kubes, Paul

    2016-04-21

    A key feature of inflammation is the timely recruitment of leukocytes, including monocytes, from blood into tissues, the latter maturing into macrophages over a period of 2-3 days. Using multi-channel spinning disk microscopy, we identified a rapid pathway of macrophage recruitment into an injured organ via a non-vascular route requiring no maturation from monocytes. In response to a sterile injury in liver, a reservoir of fully mature F4/80(hi)GATA6(+) peritoneal cavity macrophages rapidly invaded into afflicted tissue via direct recruitment across the mesothelium. The invasion was dependent on CD44 and DAMP molecule ATP and resulted in rapid replication and switching of macrophage toward an alternatively activated phenotype. These macrophages dismantled the nuclei of necrotic cells releasing DNA and forming a cover across the injury site. Rapid invasion of mature macrophages from body cavity with capacity for induction of reparative phenotype may impact altered tissues ranging from trauma to infections to cancer. VIDEO ABSTRACT. PMID:27062926

  10. Parameters of arterial function and structure in adult patients after coarctation repair.

    PubMed

    Trojnarska, Olga; Mizia-Stec, Katarzyna; Gabriel, Marcin; Szczepaniak-Chicheł, Ludwina; Katarzyńska-Szymańska, Agnieszka; Grajek, Stefan; Tykarski, Andrzej; Gąsior, Zbigniew; Kramer, Lucyna

    2011-07-01

    Regardless of a successful operation, patients with coarctation of aorta (CoAo) are exposed to the risk of hypertension and a propensity to vascular and end-organ damage. The aim of this study is to evaluate the influence of residual aorta stenosis as well as the age at the operation on the parameters of arterial function and structure in patients after CoAo repair. Eighty-five patients after CoAo repair (53 males; mean age: 34.6 ± 10.3 years, mean age at the repair: 10.9 ± 8.2 years) were enrolled in the study. The control group consisted of 30 healthy subjects (18 males; mean age: 33.6 ± 8.2 years). Indices of systemic arterial remodeling [flow-mediated dilatation (FMD), nitroglycerine-mediated vasodilatation (NMD), carotid intima-media thickness (IMT), pulse wave velocity (PWV)] were analyzed in all study patients. In normotensive patients after CoAo repair (47/55%), a significantly increased PWV was observed in comparison to the control group (6.8 ± 1.2 vs. 5.4 ± 0.9 m/s; p = 0.003), with no difference in IMT values (0.53 ± 0.1 vs. 0.51 ± 0.1 mm; p = 0.06). Mean FMD (4.8 ± 2.8 vs. 8.5 ± 2.3%; p = 0.00003) and NMD (11.3 ± 4.6 vs. 19.8 ± 7.2%; p = 0.00001) were lower than in the controls. In patients with a residual aorta stenosis (46/54%), defined as an arm-leg pressure gradient ≥ 20 mmHg, no differences were found within the scope of both systolic and diastolic blood pressure and of all of the examined vascular parameters. No significant correlations were revealed between the vascular parameters and the gradient across descending aorta as well as the age at the operation. Residual stenosis in the descending aorta does not affect the arterial vasodilatation nor stiffness in patients after CoAo repair. An early surgery does not influence the remodeling of the vessels, which supports the thesis that CoAo is a generalized vascular disease and that even an early operation cannot prevent the progressive and vascular changes and end-organ damage. PMID

  11. JH Biosynthesis by Reproductive Tissues and Corpora Allata in Adult Longhorned Beetles, Apriona germari

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report on juvenile hormone (JH) biosynthesis from long-chain intermediates by specific reproductive system tissues and the corpora allata (CA) prepared from adult longhorned beetles, Apriona germari. Testes, male accessory glands (MAGs), ovaries and CA contain the long-chain intermediates in the ...

  12. Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells.

    PubMed

    Jadhav, Unmesh; Nalapareddy, Kodandaramireddy; Saxena, Madhurima; O'Neill, Nicholas K; Pinello, Luca; Yuan, Guo-Cheng; Orkin, Stuart H; Shivdasani, Ramesh A

    2016-06-01

    Bivalent promoters in embryonic stem cells (ESCs) carry methylation marks on two lysine residues, K4 and K27, in histone3 (H3). K4me2/3 is generally considered to promote transcription, and Polycomb Repressive Complex 2 (PRC2) places K27me3, which is erased at lineage-restricted genes when ESCs differentiate in culture. Molecular defects in various PRC2 null adult tissues lack a unifying explanation. We found that epigenomes in adult mouse intestine and other self-renewing tissues show fewer and distinct bivalent promoters compared to ESCs. Groups of tissue-specific genes that carry bivalent marks are repressed, despite the presence of promoter H3K4me2/3. These are the predominant genes de-repressed in PRC2-deficient adult cells, where aberrant expression is proportional to the H3K4me2/3 levels observed at their promoters in wild-type cells. Thus, in adult animals, PRC2 specifically represses genes with acquired, tissue-restricted promoter bivalency. These findings provide new insights into specificity in chromatin-based gene regulation. PMID:27212235

  13. Sources of adult mesenchymal stem cells for ligament and tendon tissue engineering.

    PubMed

    Dhinsa, Baljinder S; Mahapatra, Anant N; Khan, Wasim S

    2014-01-01

    Tendon and ligament injuries are common, and repair slowly with reduced biomechanical properties. With increasing financial demands on the health service and patients to recover from tendon and ligament injuries faster, and with less morbidity, health professionals are exploring new treatment options. Tissue engineering may provide the answer, with its unlimited source of natural cells that in the correct environment may improve repair and regeneration of tendon and ligament tissue. Mesenchymal stem cells have demonstrated the ability to self renew and have multilineage differentiation potential. The use of bone marrow-derived mesenchymal stem cells has been reported, however significant in vitro culture expansion is required due to the low yield of cells, which has financial implications. Harvesting of bone marrow cells also has associated morbidity. Several studies have looked at alternative sources for mesenchymal stem cells. Reports in literature from animal studies have been encouraging, however further work is required. This review assesses the potential sources of mesenchymal stem cells for tissue engineering in tendons and ligaments. PMID:25012740

  14. Minimally invasive repair of pectus excavatum (MIRPE) in adults: is it a proper choice?

    PubMed Central

    Demirkaya, Ahmet; Kılıç, Burcu; Kara, Hasan Volkan; Yakşi, Osman; Alizade, Nurlan; Demirhan, Özkan; Sayılgan, Cem; Turna, Akif; Kaynak, Kamil

    2016-01-01

    Introduction The Nuss procedure is suitable for prepubertal and early pubertal patients but can also be used in adult patients. Aim To determine whether the minimally invasive technique (MIRPE) can also be performed successfully in adults. Material and methods Between July 2006 and January 2016, 836 patients (744 male, 92 female) underwent correction of pectus excavatum with the MIRPE technique at our institution. The mean age was 16.8 years (2–45 years). There were 236 adult patients (28.2%) (> 18 years) – 20 female, 216 male. The mean age among the adult patients was 23.2 years (18–45 years). The recorded data included length of hospital stay, postoperative complications, number of bars used, duration of the surgical procedure and signs of pneumothorax on the postoperative chest X-ray. Results The MIRPE was performed in 236 adult patients. The average operative time was 44.4 min (25–90 min). The median postoperative stay was 4.92 ±2.81 days (3–21 days) in adults and 4.64 ±1.58 (2–13) in younger patients. The difference was not statistically significant (p = 0.637). Two or more bars were used in 36 (15.8%) adult patients and in 44 (7.5%) younger patients. The difference was not statistically significant either (p = 0.068). Regarding the overall complications, complication rates among the adult patients and younger patients were 26.2% and 11.8% respectively. The difference was statistically significant (p = 0.007). Conclusions MIRPE is a feasible procedure that produces good long-term results in the treatment of pectus excavatum in adults. PMID:27458490

  15. β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair.

    PubMed

    Rudolf, Anja; Schirwis, Elija; Giordani, Lorenzo; Parisi, Alice; Lepper, Christoph; Taketo, Makoto Mark; Le Grand, Fabien

    2016-05-10

    Skeletal muscle regeneration relies on a pool of resident muscle stem cells called satellite cells (MuSCs). Following injury-induced destruction of the myofibers, quiescent MuSCs are activated and generate transient amplifying progenitors (myoblasts) that will fuse to form new myofibers. Here, we focus on the canonical Wnt signaling pathway and find that either conditional β-catenin disruption or activation in adult MuSCs results in perturbation of muscle regeneration. Using both in vivo and in vitro approaches, we observed that myoblasts lacking β-catenin show delayed differentiation, whereas myoblasts with constitutively active β-catenin undergo precocious growth arrest and differentiation. Transcriptome analysis further demonstrated that Wnt/β-catenin signaling interacts with multiple pathways and, more specifically, TGF-β signaling. Indeed, exogenous TGF-β2 stimulation restores the regenerative potential of muscles with targeted β-catenin disruption in MuSCs. We conclude that a precise level of β-catenin activity is essential for regulating the amplification and differentiation of MuSC descendants during adult myogenesis. PMID:27134174

  16. Concise review: The role of C-kit expressing cells in heart repair at the neonatal and adult stage.

    PubMed

    Hesse, Michael; Fleischmann, Bernd K; Kotlikoff, Michael I

    2014-07-01

    Ischemic heart disease is the number one cause of morbidity and mortality in the developed world due to the inability of the heart to replace lost myocytes. The cause of postinfarction myogenic failure has been a subject of intense scientific investigation and much controversy. Recent data indicate a brief perinatal developmental window exists during which postinfarction myogenesis, and substantial heart regeneration, occurs. By contrast, repair of an equivalent injury of the adult heart results in prominent revascularization without myogenesis. Here, we review recent experiments on neonatal postinjury myogenesis, examine the mechanistic hypotheses of dedifferentiation and precursor expansion, and discuss experiments indicating that postinfarction revascularization derives primarily from cardiac vascular precursors. These data have profound consequences for the understanding of human heart repair, as they address the long standing question as to whether human postinfarction myogenic failure is due to the loss of precursors existent at the neonatal stage or to a context-dependent inhibition of these precursors within the infarct, and suggest strategies for the recapitulation of neonatal myogenic capacity and the augmentation of revascularization. PMID:24585704

  17. Evaluation of cartilage, synovium and adipose tissue as cellular sources for osteochondral repair.

    PubMed

    Innes, J F; Gordon, C; Vaughan-Thomas, A; Rhodes, N P; Clegg, P D

    2013-09-01

    Osteochondral lesions are a major cause of pain and disability in several species including dogs, horses and human beings. The objective of this study was to assess three potential sources of canine cells for their osteochondral regenerative potential. Cartilage, synovium and adipose tissue cells were grown in pellet culture in chondrogenic or osteogenic media. Cartilage-derived pellets displayed the best chondrogenic differentiation as indicated by significantly higher COL2A1 and SOX9 mRNA expression, greater glycosaminoglycan content, and higher retention of Safranin-O stain compared to the synovium and adipose-derived cells. Following application of the osteogenic media, all three cell sources exhibited small areas of positive alizarin red staining. Poor intracellular alkaline phosphatase activity was found in all three cell types when stimulated although osteocalcin and RUNX2 expression were significantly increased. Cells isolated and cultured from canine articular cartilage retained their specific chondrocytic phenotype. Furthermore, canine adipocytes and synovial cells did not undergo chondrogenic differentiation and did not exhibit evidence of multipotency. Although osteogenic differentiation was initiated at a genomic level, phenotypic osteoblastic differentiation was not observed. The findings of this study suggest that cells isolated from canine adipose tissue and synovium are sub-optimal substitutes for chondrocytes when engineering articular cartilage in vitro. PMID:23886701

  18. Osteoconductivity of modified fluorcanasite glass-ceramics for bone tissue augmentation and repair.

    PubMed

    Bandyopadhyay-Ghosh, S; Faria, P E P; Johnson, A; Felipucci, D N B; Reaney, I M; Salata, L A; Brook, I M; Hatton, P V

    2010-09-01

    Modified fluorcanasite glasses were fabricated by either altering the molar ratios of Na(2)O and CaO or by adding P(2)O(5) to the parent stoichiometric glass compositions. Glasses were converted to glass-ceramics by a controlled two-stage heat treatment process. Rods (2 mm x 4 mm) were produced using the conventional lost-wax casting technique. Osteoconductive 45S5 bioglass was used as a reference material. Biocompatibility and osteoconductivity were investigated by implantation into healing defects (2 mm) in the midshaft of rabbit femora. Tissue response was investigated using conventional histology and scanning electron microscopy. Histological and histomorphometric evaluation of specimens after 12 weeks implantation showed significantly more bone contact with the surface of 45S5 bioglass implants when compared with other test materials. When the bone contact for each material was compared between experimental time points, the Glass-Ceramic 2 (CaO rich) group showed significant difference (p = 0.027) at 4 weeks, but no direct contact at 12 weeks. Histology and backscattered electron photomicrographs showed that modified fluorcanasite glass-ceramic implants had greater osteoconductivity than the parent stoichiometric composition. Of the new materials, fluorcanasite glass-ceramic implants modified by the addition of P(2)O(5) showed the greatest stimulation of new mineralized bone tissue formation adjacent to the implants after 4 and 12 weeks implantation. PMID:20336751

  19. Ice-templated structures for biomedical tissue repair: From physics to final scaffolds

    NASA Astrophysics Data System (ADS)

    Pawelec, K. M.; Husmann, A.; Best, S. M.; Cameron, R. E.

    2014-06-01

    Ice-templating techniques, including freeze-drying and freeze casting, are extremely versatile and can be used with a variety of materials systems. The process relies on the freezing of a water based solution. During freezing, ice nucleates within the solution and concentrates the solute in the regions between the growing crystals. Once the ice is removed via sublimation, the solute remains in a porous structure, which is a negative of the ice. As the final structure of the ice relies on the freezing of the solution, the variables which influence ice nucleation and growth alter the structure of ice-templated scaffolds. Nucleation, the initial step of freezing, can be altered by the type and concentration of solutes within the solution, as well as the set cooling rate before freezing. After nucleation, crystal growth and annealing processes, such as Ostwald ripening, determine the features of the final scaffold. Both crystal growth and annealing are sensitive to many factors including the set freezing temperature and solutes. The porous structures created using ice-templating allow scaffolds to be used for many diverse applications, from microfluidics to biomedical tissue engineering. Within the field of tissue engineering, scaffold structure can influence cellular behavior, and is thus critical for determining the biological stimulus supplied by the scaffold. The research focusing on controlling the ice-templated structure serves as a model for how other ice-templating systems might be tailored, to expand the applications of ice-templated structures to their full potential.

  20. Association and Interactions between DNA Repair Gene Polymorphisms and Adult Glioma

    PubMed Central

    Liu, Yanhong; Scheurer, Michael E.; El-Zein, Randa; Cao, Yumei; Do, Kim-Anh; Gilbert, Mark; Aldape, Kenneth D.; Wei, Qingyi; Etzel, Carol; Bondy, Melissa L.

    2010-01-01

    It is generally accepted that glioma develops through accumulation of genetic alterations. We hypothesized that polymorphisms of candidate genes involved in the DNA repair pathways may contribute to susceptibility to glioma. To address this possibility, we conducted a study of 373 Caucasian glioma cases and 365 cancer-free Caucasian controls to assess associations between glioma risk and 18 functional SNPs in DNA repair genes. We evaluated potential gene-gene and gene-environment interactions using a multi-analytic strategy combining logistic regression, multifactor dimensionality reduction (MDR), and classification and regression tree (CART) approaches. In the single-locus analysis, six SNPs (ERCC1 3’ UTR, XRCC1 R399Q, APEX1 E148D, PARP1 A762V, MGMT F84L, and LIG1 5’UTR) showed a significant association with glioma risk. In the analysis of cumulative genetic risk of multiple SNPs, a significant gene-dosage effect was found for increased glioma risk with increasing numbers of adverse genotypes involving the above-mentioned six SNPs (P trend = 0.0004). Further, both the MDR and CART analyses identified MGMT F84L as the predominant risk factor for glioma, and revealed strong interactions among ionizing radiation (IR) exposure, PARP1 A762V, MGMT F84L and APEX1 E148D. Interestingly, the risk for glioma was dramatically increased in IR exposure individuals who had the wild-type genotypes of both MGMT F84L and PARP1 A762V [adjusted odds ratios (OR), 5.95; 95% confidence intervals (CI), 2.21–16.65]. Taken together, these results suggest that polymorphisms in DNA repair genes may act individually or together to contribute to glioma risk. PMID:19124499

  1. Outcomes of Surgical Repair for Persistent Truncus Arteriosus from Neonates to Adults: A Single Center's Experience

    PubMed Central

    Chen, Qiuming; Gao, Huawei; Hua, Zhongdong; Yang, Keming; Yan, Jun; Zhang, Hao; Ma, Kai; Zhang, Sen; Qi, Lei; Li, Shoujun

    2016-01-01

    Objective This study aimed to report our experiences with surgical repair in patients of all ages with persistent truncus arteriosus. Methods From July 2004 to July 2014, 50 consecutive patients with persistent truncus arteriosus who underwent anatomical repair were included in the retrospective review. Median follow-up time was 3.4 years (range, 3 months to 10 years). Results Fifty patients underwent anatomical repair at a median age of 19.6 months (range, 20 days to 19.1 years). Thirty patients (60%) were older than one year. The preoperative pulmonary vascular resistance and mean pulmonary artery pressure were 4.1±2.1 (range, 0.1 to 8.9) units.m2 and 64.3±17.9 (range, 38 to 101) mmHg, respectively. Significant truncal valve regurgitation was presented in 14 (28%) patients. Hospital death occurred in 3 patients, two due to pulmonary hypertensive crisis and the other due to pneumonia. Three late deaths occurred at 3, 4 and 11 months after surgery. The actuarial survival rates were 87.7% and 87.7% at 1 year and 5 years, respectively. Multivariate analysis identified significant preoperative truncal valve regurgitation was a risk factor for overall mortality (odds ratio, 7.584; 95%CI: 1.335–43.092; p = 0.022). Two patients required reoperation of truncal valve replacement. One patient underwent reintervention for conduit replacement. Freedom from reoperation at 5 years was 92.9%. At latest examination, there was one patient with moderate-to-severe truncal valve regurgitation and four with moderate. Three patients had residual pulmonary artery hypertension. All survivors were in New York Heart Association class I-II. Conclusions Complete repair of persistent truncus arteriosus can be achieved with a relatively low mortality and acceptable early- and mid-term results, even in cases with late presentation. Significant preoperative truncal valve regurgitation remains a risk factor for overall mortality. The long-term outcomes warrant further follow-up. PMID:26752522

  2. Self-assembled adult adipose-derived stem cell spheroids combined with biomaterials promote wound healing in a rat skin repair model.

    PubMed

    Hsu, Shan-Hui; Hsieh, Pai-Shan

    2015-01-01

    Adult adipose-derived stem cells (ASCs) are a type of multipotent mesenchymal stem cells (MSCs) with easy availability and serve as a potential cell source for cell-based therapy. Three-dimensional MSC spheroids may be derived from the self-assembly of individual MSCs grown on certain polymer membranes. In this study, we demonstrated that the self-assembled ASC spheroids on chitosan-hyaluronan membranes expressed more cytokine genes (fibroblast growth factor 1, vascular endothelial growth factor, and chemokine [C-C motif] ligand 2) as well as migration-associated genes (chemokine [C-X-C motif] receptor type 4 and matrix metalloprotease 1) compared with ASC dispersed single cells grown on culture dish. To evaluate the in vivo effects of these spheroids, we applied ASC single cells and ASC spheroids in a designed rat skin repair model. Wounds of 15 × 15 mm were created on rat dorsal skin, where ASCs were administered and covered with hyaluronan gel/chitosan sponge to maintain a moist environment. Results showed that skin wounds treated with ASC spheroids had faster wound closure and a significantly higher ratio of angiogenesis. Tracking of fluorescently labeled ASCs showed close localization of ASC spheroids to microvessels, suggesting enhanced angiogenesis through paracrine effects. Based on the in vitro and in vivo results, the self-assembled ASC spheroids may be a promising cellular source for skin tissue engineering and wound regeneration. PMID:25421559

  3. Photochemical tissue bonding

    DOEpatents

    Redmond, Robert W.; Kochevar, Irene E.

    2012-01-10

    Photochemical tissue bonding methods include the application of a photosensitizer to a tissue and/or tissue graft, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for tissue adhesion, such as in wound closure, tissue grafting, skin grafting, musculoskeletal tissue repair, ligament or tendon repair and corneal repair.

  4. Effects of Bilingualism and Trilingualism in L2 Production: Evidence from Errors and Self-Repairs in Early Balanced Bilingual and Trilingual Adults

    ERIC Educational Resources Information Center

    Hsu, Hsiu-ling

    2014-01-01

    Through analyzing response latencies, errors, and self-repairs in Mandarin, this investigation explores how monolingual, bilingual, and trilingual adults process their speech production differently using cognitive control mechanisms. In this study we conducted two experiments involving speech production in Mandarin. In the two experiments, 81…

  5. Lysineurethanedimethacrylate--a novel generation of amino acid based monomers for bone cements and tissue repair.

    PubMed

    Müh, Ekkehard; Zimmermann, Jörg; Kneser, Ulrich; Marquardt, Jürgen; Mülhaupt, Rolf; Stark, Björn

    2002-07-01

    A novel amino acid based dimethacrylate monomer (lysineurethanedimethacrylate, LUDM) was prepared by the addition of hydroxyethylmethacrylate (HEMA) to lysinediisocyanate (LDI). The structure was confirmed by FT-IR and 1H and 13C NMR spectroscopy as well as FAB-MS. Photopolymerized LUDM exhibited low volume shrinkage upon polymerization, good mechanical properties (Young's modulus: 3740 MPa) and high thermal stability. Osteoblast adhesion and growth on polymerized LUDM samples evidenced the biocompatibility. Further improvement of the mechanical properties was obtained by using Ca-hydroxyapatite as inorganic filler varying between 10 and 30 wt%. The Young's and flexural moduli increased with increasing filler content ranging from 3740 to 5250 MPa and from 2020 to 3690 MPa, respectively. The mechanical properties and the good biocompatibility of the lysine-based methacrylate networks make them interesting materials for medical applications, e.g. bone cements, and tissue engineering. PMID:12069324

  6. Prostaglandin-secreting cells: a portable first aid kit for tissue repair

    PubMed Central

    Rakoff-Nahoum, Seth; Medzhitov, Ruslan

    2007-01-01

    After intestinal injury, both the number and type of intestinal epithelial cells must be restored. Intestinal stem cells, located at the base of the intestinal crypt, repopulate the depleted crypt in a process known as compensatory proliferation. In this issue of the JCI, Brown et al. describe a new mechanism by which this process is regulated (see the related article beginning on page 258). Surprisingly, they find that a subset of stromal cells present within the intestinal tissue and expressing the proliferative factor prostaglandin-endoperoxidase synthase 2 (Ptgs2) is repositioned next to the intestinal stem cell compartment where local production of PGE2 controls injury-induced epithelial cell proliferation. PMID:17200710

  7. Negative Pressure Wound Therapy with Surgical Gloves to Repair Soft Tissue Defects in Hands.

    PubMed

    Fujitani, Teruaki; Zenke, Yukichi; Shinone, Michitaka; Menuki, Kunitaka; Fukumoto, Keizo; Sakai, Akinori

    2015-09-01

    The efficacy of negative pressure wound therapy (NPWT) in the treatment of skin defect wounds has been established, but it is difficult to apply to hand surgery because of the easy occurrence of air leaks. We report two cases of performing NPWT with surgical gloves. Case1: A 37-year-old male was injured on his right dorsal hand from a punch. He presented to our hospital three days after the injury because of swelling and pain. The wound was infected and contused, so wound lavage and debridement (W&D) were performed under local anesthesia. The infected condition didn't improve after antimicrobial infusion, so W&D were performed again 8 days after the first visit. Then W&D were performed every day, and the infection subsided 15 days after the first visit. NPWT was initiated for the purpose of managing exudate and the wound condition, and healthy granulation tissue formed gradually. Finally, transpositional flap and full-thickness skin graft were performed on day 29. Case2: A 43-year-old male accidentally sustained a high pressure injection of oil into his dorsal hand. He presented to our hospital the next day, and W&D were performed. W&D were performed again two days after the first visit, and artificial dermis was applied over a part of the wound that was impossible to close. A decision was made to apply NPWT and a surgical glove for the purpose of reducing swelling and managing wound exudate. The swelling decreased and granulation tissue formed gradually, then nine days after the first visit a sural nerve graft was applied to bridge the defective area, and a full thickness skin graft was applied. We achieved good wound closure and hand function recovery after using NPWT and a surgical glove. PMID:26370041

  8. Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing

    PubMed Central

    Hsu, I; Parkinson, L G; Shen, Y; Toro, A; Brown, T; Zhao, H; Bleackley, R C; Granville, D J

    2014-01-01

    Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition. PMID:25299783

  9. An evaluation of Admedus' tissue engineering process-treated (ADAPT) bovine pericardium patch (CardioCel) for the repair of cardiac and vascular defects.

    PubMed

    Strange, Geoff; Brizard, Christian; Karl, Tom R; Neethling, Leon

    2015-03-01

    Tissue engineers have been seeking the 'Holy Grail' solution to calcification and cytotoxicity of implanted tissue for decades. Tissues with all of the desired qualities for surgical repair of congenital heart disease (CHD) are lacking. An anti-calcification tissue engineering process (ADAPT TEP) has been developed and applied to bovine pericardium (BP) tissue (CardioCel, AdmedusRegen Pty Ltd, Perth, WA, Australia) to eliminate cytotoxicity, improve resistance to acute and chronic inflammation, reduce calcification and facilitate controlled tissue remodeling. Clinical data in pediatric patients, and additional pre-market authorized prescriber data demonstrate that CardioCel performs extremely well in the short term and is safe and effective for a range of congenital heart deformations. These data are supported by animal studies which have shown no more than normal physiologic levels of calcification, with good durability, biocompatibility and controlled healing. PMID:25431988

  10. Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

    PubMed Central

    2013-01-01

    Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibility to stimulate their in vivo differentiation or to use their ex vivo expanded progenies for cell replacement-based therapies with multiple applications in human. Among the human diseases that could be treated by the stem cell-based therapies, there are hematopoietic and immune disorders, multiple degenerative disorders, such as Parkinson’s and Alzeimeher’s diseases, type 1 or 2 diabetes mellitus as well as eye, liver, lung, skin and cardiovascular disorders and aggressive and metastatic cancers. In addition, the genetically-modified adult stem/progenitor cells could also be used as delivery system for expressing the therapeutic molecules in specific damaged areas of different tissues. Recent advances in cancer stem/progenitor cell research also offer the possibility to targeting these undifferentiated and malignant cells that provide critical functions in cancer initiation and progression and disease relapse for treating the patients diagnosed with the advanced and metastatic cancers which remain incurable in the clinics with the current therapies. PMID:18288619

  11. Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas and other nonmuscle tissues.

    PubMed

    Di Rocco, Giuliana; Tritarelli, Alessandra; Toietta, Gabriele; Gatto, Ilaria; Iachininoto, Maria Grazia; Pagani, Francesca; Mangoni, Antonella; Straino, Stefania; Capogrossi, Maurizio C

    2008-02-01

    At the embryonic or fetal stages, autonomously myogenic cells (AMCs), i.e., cells able to spontaneously differentiate into skeletal myotubes, have been identified from several different sites other than skeletal muscle, including the vascular compartment. However, in the adult animal, AMCs from skeletal muscle-devoid tissues have been described in only two cases. One is represented by thymic myoid cells, a restricted population of committed myogenic progenitors of unknown derivation present in the thymic medulla; the other is represented by a small subset of adipose tissue-associated cells, which we recently identified. In the present study we report, for the first time, the presence of spontaneously differentiating myogenic precursors in the pancreas and in other skeletal muscle-devoid organs such as spleen and stomach, as well as in the periaortic tissue of adult mice. Immunomagnetic selection procedures indicate that AMCs derive from Flk-1(+) progenitors. Individual clones of myogenic cells from nonmuscle organs are morphologically and functionally indistinguishable from skeletal muscle-derived primary myoblasts. Moreover, they can be induced to proliferate in vitro and are able to participate in muscle regeneration in vivo. Thus, we provide evidence that fully competent myogenic progenitors can be derived from the Flk-1(+) compartment of several adult tissues that are embryologically unrelated to skeletal muscle. PMID:18094147

  12. The expression of c-kit protein in human adult and fetal tissues.

    PubMed

    Horie, K; Fujita, J; Takakura, K; Kanzaki, H; Suginami, H; Iwai, M; Nakayama, H; Mori, T

    1993-11-01

    The c-kit proto-oncogene encodes a tyrosine kinase receptor and is allelic with the dominant white-spotting (W) locus of the mouse. In this study we investigated the expression of human c-kit protein in various adult and fetal human tissues immunohistochemically using anti-human c-kit monoclonal antibody. To discriminate c-kit+ cells from mast cells expressing c-kit, mast cells were identified by staining with Toluidine blue. In oogonia, spermatogonia and skin melanocytes of the fetus and in oocytes of adult ovary, c-kit expression was detected. In adult uterus, c-kit+ cells were widely distributed in the basal layer of the endometrium, myometrium and cervix, the number and distribution being almost identical to those of mast cells. In fetal uterus, c-kit+ non-mast cells clustered beneath the epithelium and a few mast cells were observed in the myometrium and subserosal layer. In both adult and fetus, c-kit+ non-mast cells were detected within smooth muscle layers of the intestine, colon and oesophagus, while mast cells were observed in the mucosal and submucosal layers of these organs. In contrast to mice, no expression of c-kit protein was detected in the human placenta and decidua. Thus, the distribution of c-kit+ cells in various tissues is similar but not identical between adult and fetus and between human and mouse. PMID:7507133

  13. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    PubMed Central

    Dordevic, Aimee L.; Pendergast, Felicity J.; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K.; Larsen, Amy E.; Sinclair, Andrew J.; Cameron-Smith, David

    2015-01-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID:26140541

  14. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults.

    PubMed

    Dordevic, Aimee L; Pendergast, Felicity J; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K; Larsen, Amy E; Sinclair, Andrew J; Cameron-Smith, David

    2015-07-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID:26140541

  15. The two faces of metal ions: From implants rejection to tissue repair/regeneration.

    PubMed

    Vasconcelos, Daniel M; Santos, Susana G; Lamghari, Meriem; Barbosa, Mário A

    2016-04-01

    The paradigm of metallic ions as exclusive toxic agents is changing. During the last 60 years, knowledge about toxicological and immunological reactions to metal particles and ions has advanced considerably. Hip prostheses, namely metal-on-metal bearings, have prompted studies about excessive and prolonged exposure to prosthetic debris. In that context, the interactions of metal particles and ions with cells and tissues are mostly harmful, inducing immune responses that lead to osteolysis and implant failure. However, in the last decade, new strategies to promote immunomodulation and healing have emerged based on the unique properties of metallic ions. The atom-size and charge enable ions to interact with key macromolecules (e.g. proteins, nucleic acids) that affect cellular function. Moreover, these agents are inexpensive, stable and can be integrated in biomaterials, which may open new avenues for a novel generation of medical devices. Herein, orthopedic devices are discussed as models for adverse responses to metal ions, and debated together with the potential to use metal ions-based therapies, thus bridging the gap between unmet clinical needs and cutting-edge research. In summary, this review addresses the two "faces" of metallic ions, from pathological responses to innovative research strategies that use metal ions for regenerative medicine. PMID:26851391

  16. Cyanoacrylate tissue glue for wound repair in early posttrabeculectomy conjunctival bleb leak: a case series

    PubMed Central

    Haslinda, Abdul-Rahim; Azhany, Yaakub; Noor-Khairul, Rasid; Zunaina, Embong; Liza-Sharmini, Ahmad-Tajudin

    2015-01-01

    We demonstrated a noninvasive management of early bleb leak following trabeculectomy using cyanoacrylate tissue glue (CATG). Three patients who underwent augmented trabeculectomy with mitomycin C with early bleb leak between January 2009 and June 2010 were reviewed. Case 1 and Case 2 exhibited bleb leak on postoperative Day 1 and Case 3 showed leak on follow-up at postoperative Day 7. Case 1 was successfully sealed with CATG at postoperative Day 3, after failed pressure padding and bandage contact lens. Case 2 was successfully sealed with CATG at postoperative Day 3, after failed pressure padding and conjunctiva flap resuturing. In Case 3, the leaking conjunctival flap was managed with combined techniques of resuturing and applying CATG at postoperative Day 9, after failed pressure padding. During leakage, the intraocular pressure was low (6–8 mmHg) in all three cases, with shallow anterior chamber depth and absence of other complications such as choroidal detachment, hypotony maculopathy, or endophthalmitis. Foreign body sensation was the main complaint following the procedure. No clinical allergy reaction was documented. CATG may serve as a potential adjunctive and effective method in the management of posttrabeculectomy early bleb leak. PMID:26229511

  17. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue

    PubMed Central

    Klaas, Mariliis; Kangur, Triin; Viil, Janeli; Mäemets-Allas, Kristina; Minajeva, Ave; Vadi, Krista; Antsov, Mikk; Lapidus, Natalia; Järvekülg, Martin; Jaks, Viljar

    2016-01-01

    While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue. PMID:27264108

  18. Plasticity in the Adult: How Should the Waddington Diagram Be Applied to Regenerating Tissues?

    PubMed

    Rajagopal, Jayaraj; Stanger, Ben Z

    2016-01-25

    Conrad Waddington's eponymous 1957 diagram provided a metaphorical framework for considering how sequential developmental fate decisions allow an egg to develop into an embryo. In recent years, the Waddington diagram has been repurposed to illustrate how cellular identity changes in the context of reprogramming. In this Perspective, we revisit the Waddington diagram in light of the emerging recognition that plasticity is part and parcel of adult regeneration. Specifically, we speculate that the "epigenetic landscapes" that define identity in adult tissues are dynamic, facilitating cellular de-differentiation and trans-differentiation in the setting of injury. PMID:26812013

  19. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Brown, Ronald P.; Fisher, Jeffrey W.

    2011-09-15

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral

  20. Adult mesenchymal stem cells in neural regeneration and repair: Current advances and future prospects (Review).

    PubMed

    Trzaska, Katarzyna A; Castillo, Marianne D; Rameshwar, Pranela

    2008-01-01

    Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine as they can be easily isolated from bone marrow (BM) aspirates and expanded in culture while maintaining their 'stemness'. In addition to differentiating into mesodermal cells, MSCs have shown considerable plasticity and generate ectodermal neurons and glia, which can be used to replace cells damaged by neurological diseases and injuries. These unique stem cells also exhibit immunomodulatory functions and secrete a variety of trophic factors which support regeneration and repair. This review focuses on the therapeutic usage of MSCs for neurodegenerative diseases and traumatic injuries to the nervous system. Animal studies demonstrate great promise for MSC transplantation in neurological disorders. In fact, a few clinical trials have already been initiated and show that MSCs are a safe cellular therapy and have great potential to become a viable treatment for neural disorders in the years to come. PMID:21479411

  1. Regional anaesthesia for surgical repair in selected open globe injuries in adults

    PubMed Central

    Chakraborty, Arunangshu; Bandyopadhyay, Samir K.; Mukhopadhyay, Somnath

    2012-01-01

    Purpose To determine whether the combination of topical, intracameral and facial nerve blocks would produce adequate analgesia for repair of open globe injuries without increasing intraocular tension. Methods A comparison of combined O’Brien’s block (facial nerve block), topical ropivacaine and intracameral lignocaine versus peribulbar block in 100 randomly selected cases of traumatic corneal rupture. Patients were randomly divided in two groups of 50 each based on those receiving the combined approach (Group T) and those undergoing peribulbar block (Group P). Patients were excluded if there was rupture with significant scleral extension, the interval between trauma and presentation greater than 2 h, presence of hypopyon, rupture with significant corneal oedema, expulsion of intraocular contents with a collapsed globe and monocular cases. The effect of the anaesthetic was compared by patient comfort and surgeon comfort, the incidence of vitreous prolapse and the requirement of incremental sedation. The Student’s “t” test, the “Z” test, and Chi Square tests were used where appropriate. P < 0.05 was considered statistically significant. Results The average patient comfort in Group P was 5.67% greater than Group T (P > 0.05). The average surgeon comfort and patient comfort between groups were similar (P > 0.05, both comparisons). Incremental sedation was required in 16% of patients in Group T compared to 8% in Group P (P = 0.218363). The total sedation dosage required for each group was similar. The incidence of vitreous prolapse was statistically significantly higher by 14% in Group P compared to Group T (P = 0.03731). Conclusions Our combined technique proved as efficacious as peribulbar block in providing adequate local anaesthesia and reducing the incidence of vitreous prolapse. We recommend greater use of this technique for repair of open globe injuries especially in locations where full time anaesthesia services are not available. PMID

  2. Comparison of international guidelines for regenerative medicine: Knee cartilage repair and replacement using human-derived cells and tissues.

    PubMed

    Itoh, Kuni; Kano, Shingo

    2016-07-01

    Regenerative medicine (RM) is an emerging field using human-derived cells and tissues (HCT). Due to the complexity and diversity of HCT products, each country has its own regulations for authorization and no common method has been applied to date. Individual regulations were previously clarified at the level of statutes but no direct comparison has been reported at the level of guidelines. Here, we generated a new analytical framework that allows comparison of guidelines independent from local definitions of RM, using 2 indicators, product type and information type. The guidelines for products for repair and replacement of knee cartilage in Japan, the United States of America, and Europe were compared and differences were detected in both product type and information type by the proposed analytical framework. Those findings will be critical not only for the product developers to determine the region to initiate the clinical trials but also for the regulators to assess and build their regulations. This analytical framework is potentially expandable to other RM guidelines to identify gaps, leading to trigger discussion of global harmonization in RM regulations. PMID:27156144

  3. Dietary Iron Concentration May Influence Aging Process by Altering Oxidative Stress in Tissues of Adult Rats

    PubMed Central

    Arruda, Lorena Fernandes; Arruda, Sandra Fernandes; Campos, Natália Aboudib; de Valencia, Fernando Fortes; Siqueira, Egle Machado de Almeida

    2013-01-01

    Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively) for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl) and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b) and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2) and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2) relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging. PMID:23593390

  4. Adipogenic potential in human mesenchymal stem cells strictly depends on adult or foetal tissue harvest.

    PubMed

    Ragni, Enrico; Viganò, Mariele; Parazzi, Valentina; Montemurro, Tiziana; Montelatici, Elisa; Lavazza, Cristiana; Budelli, Silvia; Vecchini, Alba; Rebulla, Paolo; Giordano, Rosaria; Lazzari, Lorenza

    2013-11-01

    Cell-based therapies promise important developments for regenerative medicine purposes. Adipose tissue and the adipogenic process has become central to an increasing number of translational efforts in addition to plastic and reconstructive surgical applications. In recent experimental clinical trials, human mesenchymal stem cells (MSC) have been proven to be well tolerated because of their low immunoreactivity. MSC are multipotent cells found among mature cells in different tissues and organs with the potentiality to differentiate in many cell types, including osteocytes, chondrocytes and adipocytes, thus being a suitable cell source for tissue engineering strategies. We compared the adipogenic potential of MSC originated from two adult sources as fat pads and bone marrow, and from four foetal sources as umbilical cord blood, Wharton's jelly, amniotic fluid and preterm umbilical cord perivascular cells. Surprisingly, adult MSC displayed higher differentiation capacities confirmed by gene expression analysis on a selected panel of adipogenesis-related genes. Further, an in-depth molecular analysis highlighted the early and vigorous activation of the PPARγ transcription factor-cascade in adipose-derived MSC that resulted to be both delayed and reduced in foetal MSC accounting for their lack of adipogenic potential. Thus, MSC show a different degree of phenotypic plasticity depending on the source tissue, that should be taken into consideration for the selection of the most appropriate MSC type for specific tissue regeneration purposes. PMID:23942228

  5. Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue.

    PubMed

    Simbulan, R K; Liu, X; Feuer, S K; Maltepe, E; Donjacour, A; Rinaudo, P

    2016-02-01

    Prenatal development is highly plastic and readily influenced by the environment. Adverse conditions have been shown to alter organ development and predispose offspring to chronic diseases, including diabetes and hypertension. Notably, it appears that the changes in glucocorticoid hormones or glucocorticoid receptor (GR) levels in peripheral tissues could play a role in the development of chronic diseases. We have previously demonstrated that in vitro fertilization (IVF) and preimplantation embryo culture is associated with growth alterations and glucose intolerance in mice. However, it is unknown if GR signaling is affected in adult IVF offspring. Here we show that GR expression is increased in inbred (C57Bl6/J) and outbred (CF-1× B6D2F1/J) blastocysts following in vitro culture and elevated levels are also present in the adipose tissue of adult male mice. Importantly, genes involved in lipolysis and triglyceride synthesis and responsive to GR were also increased in adipose tissue, indicating that increased GR activates downstream gene pathways. The promoter region of GR, previously reported to be epigenetically modified by perinatal manipulation, showed no changes in DNA methylation status. Our findings demonstrate that IVF results in a long-term change in GR gene expression in a sex- and tissue-specific manner. These changes in adipose tissues may well contribute to the metabolic phenotype in mice conceived by IVF. PMID:26511158

  6. Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

    PubMed Central

    Zuliani-Alvarez, Lorena; Midwood, Kim S.

    2015-01-01

    Significance: Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. Recent Advances: An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Critical Issues: Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Future Directions: Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing. PMID:26005593

  7. Computational analysis of cartilage implants based on an interpenetrated polymer network for tissue repairing.

    PubMed

    Manzano, Sara; Poveda-Reyes, Sara; Ferrer, Gloria Gallego; Ochoa, Ignacio; Hamdy Doweidar, Mohamed

    2014-10-01

    distribution in healthy cartilage tissue. The obtained results show how the model predicts the permeability of the PEA-PHEA hydrogels and simulates the internal behaviour of the samples and shows the distribution and quantification of fluid flux. PMID:24997064

  8. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    SciTech Connect

    Kabiri, Azadeh; Esfandiari, Ebrahim; Hashemibeni, Batool; Kazemi, Mohammad; Mardani, Mohammad; Esmaeili, Abolghasem

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  9. A Case of Severe Unicuspid Aortic Valve Stenosis: Valve Repair With Tricuspidization in an Adult.

    PubMed

    Tokue, Masahide; Hara, Hidehiko; Sahara, Naohiko; Yamazaki, Kenji; Yamashita, Hiromasa; Takahashi, Kei; Ozaki, Shigeyuki; Sugi, Kaoru; Nakamura, Masato

    2015-10-01

    A 33-year-old male was referred to our institute with acute heart failure. The patient was found to have a unicuspid aortic valve (UAV) and severe aortic stenosis. He had been followed at a local university hospital during childhood. However, he stopped visiting the outpatient clinic after becoming an adult. His condition subsequently worsened, and he ultimately presented to our hospital with cardiogenic shock. In Japan, some adult congenital heart disease (ACHD) patients continue to be followed by pediatric cardiologists, though the patterns of practice are variable. This report describes the case of a patient who became lost to follow-up in early adulthood. We thus focus on this ACHD case as an example of the effects of inadequate communication among doctors and the need to establish better ACHD management protocols for treating this patient population. PMID:26467883

  10. Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair

    SciTech Connect

    Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan A.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-03-01

    Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-L-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate {beta}-lyase, the enzyme that bioactivates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephroprotection. These findings suggest that preplacement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure.

  11. Classification and Subtype Prediction of Adult Soft Tissue Sarcoma by Functional Genomics

    PubMed Central

    Segal, Neil H.; Pavlidis, Paul; Antonescu, Cristina R.; Maki, Robert G.; Noble, William S.; DeSantis, Diann; Woodruff, James M.; Lewis, Jonathan J.; Brennan, Murray F.; Houghton, Alan N.; Cordon-Cardo, Carlos

    2003-01-01

    Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma. PMID:12875988

  12. TissuePatch™ as a novel synthetic sealant for repair of superficial lung defect: in vitro tests results

    PubMed Central

    2012-01-01

    Background Controversies surrounding the efficacy of surgical sealants against alveolar air leaks (AAL) in lung surgery abound in the literature. We sought to test the sealing efficacy of a novel synthetic sealant, TissuePatch™ in an in vitro lung model. Methods The lower lobe of freshly excised swine lung (n = 10) was intubated and ventilated. A superficial parenchymal defect (40 × 25 mm) was created, followed by AAL assessment. After sealant application, AAL was assessed again until burst failure occurred. The length of defect was recorded to evaluate the elasticity of the sealant. Results Superficial parenchymal defects resulted in AAL increasing disproportionally with ascending maximal inspiratory pressure (Pmax). Multiple linear regression analysis revealed strong correlation between AAL and Pmax, compliance, resistance. After sealant application, AAL was sealed in all ten tests at an inspired tidal volume (TVi) of 400 ml, in nine tests at TVi = 500 ml, in seven at TVi = 600 ml and in five at TVi = 700 ml. The mean burst pressure was 42 ± 9 mBar. Adhesive and cohesive sealant failures were found in six and three tests respectively. The length of defect before sealant failure was 8.9 ± 4.9% larger than that at TVi = 400 ml, demonstrating an adequate elasticity of this sealant film. Conclusions TissuePatch™ may be a reliable sealant for alternative or adjunctive treatment for repair of superficial parenchymal defects in lung surgery. The clinical benefits of this sealant should be confirmed by prospective, randomised controlled clinical trials. Abstrakt Hintergrund Die Wirksamkeit von chirurgischen Klebstoffen zur Prävention von alveolo-pleuralem Luftleck (APL) ist trotz zunehmenden klinischen Anwendungen in Lungenchirurgie immer noch kontrovers diskutiert. Wir evaluierten die Abdichtungswirksamkeit von einem neuartigen synthetischen Kleber, TissuePatch™ mittels eines in vitro Lungenmodels. Methode Der Unterlappen von

  13. Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

    PubMed Central

    Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R.; High, Kevin P.; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S.; Kovacs, Elizabeth J.; Margolish, David; McFarland Horne, Frances; Reed, May J.; Sullivan, Dennis H.; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, JoAnne; Williams, John; Zieman, Susan; Schmader, Kenneth

    2014-01-01

    The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing. PMID:25486905

  14. Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

    PubMed Central

    Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R.; High, Kevin P.; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S.; Kovacs, Elizabeth J.; Margolis, David; Horne, Frances McFarland; Reed, May J.; Sullivan, Dennis H.; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, Jo Anne; Williams, John; Zieman, Susan; Schmader, Kenneth

    2015-01-01

    Older adults are more likely to have chronic wounds than younger people, and the effect of chronic wounds on quality of life is particularly profound in this population. Wound healing slows with age, but the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The effect of age and accompanying multimorbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables; lack of standardization in data collection; and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this article, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify research questions to guide future study of age-associated changes in chronic wound healing. PMID:25753048

  15. Chronic wound repair and healing in older adults: current status and future research.

    PubMed

    Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R; High, Kevin P; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S; Kovacs, Elizabeth J; Margolis, David; McFarland Horne, Frances; Reed, May J; Sullivan, Dennis H; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, Jo Anne; Williams, John; Zieman, Susan; Schmader, Kenneth

    2015-03-01

    Older adults are more likely to have chronic wounds than younger people, and the effect of chronic wounds on quality of life is particularly profound in this population. Wound healing slows with age, but the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The effect of age and accompanying multimorbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables; lack of standardization in data collection; and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this article, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify research questions to guide future study of age-associated changes in chronic wound healing. PMID:25753048

  16. The Effect of Continuous Sedation Therapy on Immunomodulation, Plasma Levels of Antioxidants, and Indicators of Tissue Repair in Post-Burn Sepsis Patients.

    PubMed

    Chen, Li; Meng, Ke; Su, Wei; Fu, Yanjie

    2015-11-01

    Our objective was to investigate the effect of continuous therapeutic sedation on the immune response, plasma levels of antioxidants, and tissue repair indicators in burn-induced sepsis patients. A total of 104 burn-induced sepsis patients hospitalized during March, 2008 to March, 2013 were selected for the study and randomly divided into the experimental and control groups, each with 53 cases. All of these patients received conventional treatment and the patients in the experimental group were given an additional therapy of continuous sedation. The number of T lymphocytes, plasma levels of tissue repair indicators, and antioxidants were measured before and after the treatment. Continuous midazolam treatment induced a significant increase in plasma levels of gelsolin, heat shock protein 70, nitric oxide, superoxide dismutase, and tumor necrosis factor-alpha (p < 0.05). Likewise, the relative counts of CD3(+), CD4(+), CD8(+) T lymphocytes, T cells exhibiting HLA-DR and CD4(+)/CD8(+) ratio were significantly increased in the patients treated with midazolam. No adverse reaction including respiratory depression, midazolam resistance, or withdrawal syndrome was observed. Continuous sedation therapy was found to enhance immune response, increase the plasma levels of antioxidants, and tissue protective/repair mediators in burn-induced sepsis patients. This therapy caused no adverse reaction or over-inhibition of the oxidative stress suggesting its effectiveness in improving the prognosis without the risk of safety. PMID:27352341

  17. Up-regulation of Thrombospondin-2 in Akt1-null Mice Contributes to Compromised Tissue Repair Due to Abnormalities in Fibroblast Function*

    PubMed Central

    Bancroft, Tara; Bouaouina, Mohamed; Roberts, Sophia; Lee, Monica; Calderwood, David A.; Schwartz, Martin; Simons, Michael; Sessa, William C.; Kyriakides, Themis R.

    2015-01-01

    Vascular remodeling is essential for tissue repair and is regulated by multiple factors, including thrombospondin-2 (TSP2) and hypoxia/VEGF-induced activation of Akt. In contrast to TSP2 knock-out (KO) mice, Akt1 KO mice have elevated TSP2 expression and delayed tissue repair. To investigate the contribution of increased TSP2 to Akt1 KO mice phenotypes, we generated Akt1/TSP2 double KO (DKO) mice. Full-thickness excisional wounds in DKO mice healed at an accelerated rate when compared with Akt1 KO mice. Isolated dermal Akt1 KO fibroblasts expressed increased TSP2 and displayed altered morphology and defects in migration and adhesion. These defects were rescued in DKO fibroblasts or after TSP2 knockdown. Conversely, the addition of exogenous TSP2 to WT cells induced cell morphology and migration rates that were similar to those of Akt1 KO cells. Akt1 KO fibroblasts displayed reduced adhesion to fibronectin with manganese stimulation when compared with WT and DKO cells, revealing an Akt1-dependent role for TSP2 in regulating integrin-mediated adhesions; however, this effect was not due to changes in β1 integrin surface expression or activation. Consistent with these results, Akt1 KO fibroblasts displayed reduced Rac1 activation that was dependent upon expression of TSP2 and could be rescued by a constitutively active Rac mutant. Our observations show that repression of TSP2 expression is a critical aspect of Akt1 function in tissue repair. PMID:25389299

  18. Elucidating the cellular actions of demineralised dentine matrix extract on a clonal dental pulp stem cell population in orchestrating dental tissue repair

    PubMed Central

    Lee, Chi P; Colombo, John S; Ayre, Wayne Nishio; Sloan, Alastair J

    2015-01-01

    Bioactive growth factors identified within the extracellular matrix of dentine have been proposed roles in regulating the naturally inherent regenerative dentine formation seen in teeth in response to trauma and infection, which may also be harnessed for novel clinical treatments in augmenting mineralised tissue repair. This study examined the specific biological action of demineralised dentine matrix extract on a clonal population of dental pulp stem cells in stimulating the prerequisite stages of wound healing associated with mineralised tissue repair. A clonal dental pulp stem cell population with sustained proliferative capacity and multi-potentiality towards osteogenic, adipogenic and chondrogenic lineages was isolated from the pulp of human third molars. Dentine was collected from human healthy teeth, powdered and treated with ethylenediaminetetraacetic acid to obtain a solubilised DDM protein extract. The influence of DDM on the DPSC clonal population was assessed in vitro. Exposure of cells to proteolytically degraded DDM or unsupplemented media served as controls. Compared to controls, DDM stimulated cell expansion, reduced apoptotic marker caspase 3, increased cell survival marker Akt1 and enhanced mineralised matrix deposition as determined by mineral deposition and increased expression of bone-related markers, alkaline phosphatase and osteopontin. Dental pulp stem cells successfully migrated into collagen gels supplemented with demineralised dentine matrix, with cells remaining viable and expanding in numbers over a 3-day period. Collectively, the results provide evidence that soluble proteins extracted from dentine matrix are able to exert a direct biological effect on dental pulp stem cells in promoting mineralised tissue repair mechanisms. PMID:26019808

  19. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis).

    PubMed

    Honeyfield, Dale C; Ross, J Perran; Carbonneau, Dwayne A; Terrell, Scott P; Woodward, Allan R; Schoeb, Trenton R; Perceval, H Franklin; Hinterkopf, Joy P

    2008-04-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B(1)) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. PMID:18436661

  20. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis)

    USGS Publications Warehouse

    Honeyfield, D.C.; Ross, J.P.; Carbonneau, D.A.; Terrell, S.P.; Woodward, A.R.; Schoeb, T.R.; Perceval, H.F.; Hinterkopf, J.P.

    2008-01-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B"1) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. ?? Wildlife Disease Association 2008.

  1. Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms.

    PubMed

    Pierce, G F; Mustoe, T A; Lingelbach, J; Masakowski, V R; Griffin, G L; Senior, R M; Deuel, T F

    1989-07-01

    Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) markedly potentiate tissue repair in vivo. In the present experiments, both in vitro and in vivo responses to PDGF and TGF-beta were tested to identify mechanisms whereby these growth factors might each enhance the wound-healing response. Recombinant human PDGF B-chain homodimers (PDGF-BB) and TGF-beta 1 had identical dose-response curves in chemotactic assays with monocytes and fibroblasts as the natural proteins from platelets. Single applications of PDGF-BB (2 micrograms, 80 pmol) and TGF-beta 1 (20 micrograms, 600 pmol) were next applied to linear incisions in rats and each enhanced the strength required to disrupt the wounds at 5 d up to 212% of paired control wounds. Histological analysis of treated wounds demonstrated an in vivo chemotactic response of macrophages and fibroblasts to both PDGF-BB and to TGF-beta 1 but the response to TGF-beta 1 was significantly less than that observed with PDGF-BB. Marked increases of procollagen type I were observed by immunohistochemical staining in fibroblasts in treated wounds during the first week. The augmented breaking strength of TGF-beta 1 was not observed 2 and 3 wk after wounding. However, the positive influence of PDGF-BB on wound breaking strength persisted through the 7 wk of testing. Furthermore, PDGF-BB-treated wounds had persistently increased numbers of fibroblasts and granulation tissue through day 21, whereas the enhanced cellular influx in TGF-beta 1-treated wounds was not detectable beyond day 7. Wound macrophages and fibroblasts from PDGF-BB-treated wounds contained sharply increased levels of immunohistochemically detectable intracellular TGF-beta. Furthermore, PDGF-BB in vitro induced a marked, time-dependent stimulation of TGF-beta mRNA levels in cultured normal rat kidney fibroblasts. The results suggest that TGF-beta transiently attracts fibroblasts into the wound and may stimulate collagen synthesis directly. In

  2. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer

    PubMed Central

    Ou, Jingxing; Vijayasarathy, Camasamudram; Ziccardi, Lucia; Chen, Shan; Zeng, Yong; Marangoni, Dario; Pope, Jodie G.; Bush, Ronald A.; Wu, Zhijian; Li, Wei; Sieving, Paul A.

    2015-01-01

    Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor–depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1–signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology. PMID:26098217

  3. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer.

    PubMed

    Ou, Jingxing; Vijayasarathy, Camasamudram; Ziccardi, Lucia; Chen, Shan; Zeng, Yong; Marangoni, Dario; Pope, Jodie G; Bush, Ronald A; Wu, Zhijian; Li, Wei; Sieving, Paul A

    2015-07-01

    Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology. PMID:26098217

  4. Dose- and time-dependent effects of genipin crosslinking on cell viability and tissue mechanics - toward clinical application for tendon repair.

    PubMed

    Fessel, Gion; Cadby, Jennifer; Wunderli, Stefania; van Weeren, René; Snedeker, Jess G

    2014-05-01

    The crosslinking agent genipin is increasingly invoked for the mechanical augmentation of collagen tissues and implants, and has previously been demonstrated to arrest mechanical damage accumulation in various tissues. This study established an in vitro dose-response baseline for the effects of genipin treatment on tendon cells and their matrix, with a view to in vivo application to the repair of partial tendon tears. Regression models based on a broad range of experimental data were used to delineate the range of concentrations that are likely to achieve functionally effective crosslinking, and predict the corresponding degree of cell loss and diminished metabolic activity that can be expected. On these data, it was concluded that rapid mechanical augmentation of tissue properties can only be achieved by accepting some degree of cytotoxicity, yet that post-treatment cell survival may be adequate to eventually repopulate and stabilize the tissue. On this basis, development of delivery strategies and subsequent in vivo study seems warranted. PMID:24384123

  5. Adult Stem Cells Seeded on Electrospinning Silk Fibroin Nanofiberous Scaffold Enhance Wound Repair and Regeneration.

    PubMed

    Xie, Sheng-Yang; Peng, Li-Hua; Shan, Ying-Hui; Niu, Jie; Xiong, Jie; Gao, Jian-Qing

    2016-06-01

    Development of novel strategy stimulating the healing with skin appendages regeneration is the critical goal for wound therapy. In this study, influence of the transplantation of bone marrow derived mesenchymal stem cells (MSCs) and epidermal stem cells (ESCs) with the nanofiberous scaffold prepared from silk fibroin protein in wound re-epithelization, collagen synthesis, as well as the skin appendages regeneration were investigated. It was shown that both the transplantation of MSCs and ESCs could significantly accelerate the skin re-epithelization, stimulate the collagen synthesis. Furthermore, the regenerative features of MSCs and ESCs in activating the blood vessels and hair follicles formation, respectively were suggested. These results demonstrated that the electrospinning nanofiberous scaffold is an advantageous carrier for the cells transplantation, but also provided the experimental proofs for the application of MSCs and ESCs as promising therapeutics in skin tissue engineering. PMID:27427589

  6. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    PubMed

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches. PMID:16989722

  7. Adult mice transplanted with embryonic retinal progenitor cells: New approach for repairing damaged optic nerves

    PubMed Central

    Cho, Jang-Hyeon; Mao, Chai-An

    2012-01-01

    Purpose Retinal ganglion cell (RGC) death and optic nerve degeneration are complex processes whose underlying molecular mechanisms are only vaguely understood. Treatments commonly used for optic nerve degeneration have little long-term value and only prolong degeneration. Recent advances in stem cell replacement therapy offer new ways to overcome RGC loss by transferring healthy cells into eyes of afflicted individuals. However, studies on stem cell replacement for optic nerve degeneration are hampered by limitations of the available animal models, especially genetic models. We have developed a mouse model in which RGCs are genetically ablated in adult mice with subsequent degeneration of the optic nerve. In the study reported here, we used this model to determine whether embryonic retinal progenitor cells (RPCs) removed from donor retinas when RPCs are committing to an RGC fate could restore lost RGCs. Methods We used the RGC-depleted model as a host for transplanting donor green fluorescent protein (GFP)–labeled RPCs from embryonic retinas that are maximally expressing Atoh7, a basic helix–loop–helix gene essential for RGC specification. Dissociated GFP-labeled RPCs were characterized in situ by immunolabeling with antibodies against proteins known to be expressed in RPCs at embryonic day (E)14.5. Dissociated retinal cells were injected into the vitreous of one eye of RGC-depleted mice at two to six months of age. The injected and non-injected retinas were analyzed for gene expression using immunolabeling, and the morphology of optic nerves was assessed visually and with histological staining at different times up to four months after injection. Results We demonstrate the successful transfer of embryonic GFP-labeled RPCs into the eyes of RGC-depleted mice. Many transplanted RPCs invaded the ganglion cell layer, but the efficiency of the invasion was low. GFP-labeled cells within the ganglion cell layer expressed genes associated with early and late stages

  8. Improvement in the repair of defects in maxillofacial soft tissue in irradiated minipigs by a mixture of adipose-derived stem cells and platelet-rich fibrin.

    PubMed

    Chen, Yuanzheng; Niu, Zhanguo; Xue, Yan; Yuan, Fukang; Fu, Yanjie; Bai, Nan

    2014-10-01

    To find out if adipose-derived stem cells (ASC) and platelet-rich fibrin (PRF), alone or combined, had any effect on the repair of maxillofacial soft tissue defects in irradiated minipigs, ASC were isolated, characterised, and expanded. Twenty female minipigs, the right parotid glands of which had been irradiated, were randomly divided into 4 groups of 5 each: those in the first group were injected with both ASC and PRF (combined group), the second group was injected with ASC alone (ASC group), the third group with PRF alone (PRF group), and the fourth group with phosphate buffer saline (PBS) (control group). Six months after the last injection, the size and depth of each defect were assessed, and subcutaneous tissues were harvested, stained with haematoxylin and eosin, and examined immunohistologically and for apoptosis. Expanded cells were successfully isolated and identified. Six months after injection the defects in the 3 treated groups were significantly smaller (p<0.001) and shallower (p<0.001) than those in the control group. Those in the combined group were the smallest and shallowest. Haematoxylin and eosin showed that the 3 treated groups contained more subcutaneous adipose tissue than the control group, and also had significantly greater vascular density (p<0.001) and fewer apoptotic cells (p<0.001). Both ASC and PRF facilitate the repair of defects in maxillofacial soft tissue in irradiated minipigs, and their combined use is more effective than their use as single agents. PMID:24993354

  9. Reconstructing spinal dura-like tissue using electrospun poly(lactide-co-glycolide) membranes and dermal fibroblasts to seamlessly repair spinal dural defects in goats.

    PubMed

    Yu, Fengbin; Li, Qiang; Yin, Shuo; Liao, Xinyuan; Huang, Fei; Chen, Deyu; Cao, Yilin; Cen, Lian

    2015-09-01

    Many neuro- and spinal surgeries involving access to the underlying nervous tissue will cause defect of spinal dural mater, further resulting in cerebrospinal fluid leakage. The current work was thus aimed to develop a package which included two layers of novel electrospun membranes, dermal fibroblasts and mussel adhesive protein for repairing spinal dural defect. The inner layer is electrospun fibrous poly(lactide-co-glycolide) membrane with oriented microstructure (O-poly(lactide-co-glycolide)), which was used as a substrate to anchor dermal fibroblasts as seed cells to reconstitute dura-like tissue via tissue engineering technique. The outer layer is chitosan-coated electrospun nonwoven poly(lactide-co-glycolide) membrane (poly(lactide-co-glycolide)-chitosan). During surgery, the inner reconstituted tissue layer was first used to directly cover dura defects, while the outer layer was placed onwards with its marginal area tightly immobilized to the surrounding normal spinal dura aided by mussel adhesive protein. Efficacy of the current design was verified in goats with spinal dural defects (0.6 cm × 0.5 cm) in lumbar. It was shown that seamless and quick sealing of the defect area with the implants was realized by mussel adhesive protein. Guided tissue growth and regeneration in the defects of goats were observed when they were repaired by the current package. Effective cerebrospinal fluid containment and anti-adhesion of the regenerated tissue to the surrounding tissue could be achieved in the current animal model. Hence, it could be ascertained that the current package could be a favorite choice for surgeries involving spinal dural defects. PMID:26041755

  10. INTERINDIVIDUAL VARIATION IN SERUM CHOLESTEROL IS ASSOCIATED WITH REGIONAL WHITE MATTER TISSUE INTEGRITY IN OLDER ADULTS

    PubMed Central

    Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; McGlinchey, Regina E.; Milberg, William P.; Rudolph, James L.; Lipsitz, Lewis A.; Salat, David H.

    2013-01-01

    Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43–87 years. Whole-brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal inter-individual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol-associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular-related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults. PMID:22438182

  11. Periodontal implications of orthodontic treatment in adults with reduced or normal periodontal tissues versus those of adolescents.

    PubMed

    Boyd, R L; Leggott, P J; Quinn, R S; Eakle, W S; Chambers, D

    1989-09-01

    This longitudinal study monitored periodontal status in 20 adults and 20 adolescents undergoing fixed orthodontic treatment. Ten adults had generalized periodontitis and received periodontal treatment, including periodontal surgery, before orthodontic treatment. They also received periodontal maintenance at 3-month intervals during orthodontic treatment. The other 10 adults had normal periodontal tissues. Neither these latter adults nor the adolescents received periodontal maintenance during orthodontic treatment. Periodontal status was determined (1) at six standard sites before fixed appliances were placed (baseline), (2) at 1, 3, 6, 9, 12, and 18 months after appliances had been placed, and (3) 1, 3, 6, and 12 months after appliances had been removed. At each of these visits, these sites were assessed for plaque index, gingival index, bleeding tendency, and pocket depth. Loss of attachment between baseline and 3 months after appliances were removed and tooth loss were also determined. Complete data were obtained for 15 adolescents and 14 adults. During orthodontic treatment the adolescent group showed significantly more (p less than 0.05) periodontal inflammation and supragingival plaque than the adults; after appliances were removed, this pattern was no longer statistically significant. For loss of attachment, there were no significant differences among adolescents, adults with normal periodontal tissues, or adults with reduced but healthy periodontal tissues who had undergone treatment for periodontal disease. For tooth loss, three nonstudy site teeth with pockets deeper than 6 mm and/or furcation involvements were lost because of periodontal abscesses in the adult group treated for periodontal disease. PMID:2773862

  12. Expression of tissue polypeptide antigen (TPA) in fetal and adult liver: changes in liver disease.

    PubMed Central

    Burt, A D; Stewart, J A; Aitchison, M; MacSween, R N

    1987-01-01

    The distribution of tissue polypeptide antigen (40 kD molecular weight) in normal adult and fetal liver, and in liver disease was investigated and compared with the distribution of low and high molecular weight cytokeratins. In normal liver tissue polypeptide antigen was found only in bile duct epithelium; this distribution is similar to that of high molecular weight cytokeratin, but differs from that of low molecular weight cytokeratins. In liver disease it was found in areas of ductular transformation; in Mallory's bodies; and in alcoholic liver disease and primary biliary cirrhosis in some hepatocytes that did not contain Mallory's bodies. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 PMID:2442199

  13. Cyclin-Dependent Kinase 5 Mediates Adult OPC Maturation and Myelin Repair through Modulation of Akt and GsK-3β Signaling

    PubMed Central

    Luo, FuCheng; Burke, Kathryn; Kantor, Christopher

    2014-01-01

    Failure of remyelination in diseases, such as multiple sclerosis (MS), leads to permanent axonal damage and irreversible functional loss. The mechanisms controlling remyelination are currently poorly understood. Recent studies implicate the cyclin-dependent kinase 5 (Cdk5) in regulating oligodendrocyte (OL) development and myelination in CNS. In this study, we show that Cdk5 is also an important regulator of remyelination. Pharmacological inhibition of Cdk5 inhibits repair of lysolecithin lesions. This inhibition is a consequence of Cdk5 disruption in neural cells because remyelination in slice cultures is blocked by Cdk5 inhibitors, whereas specific deletion of Cdk5 in OLs inhibits myelin repair. In CNP-Cre;Cdk5fl/fl conditional knock-out mouse (Cdk5 cKO), myelin repair was delayed significantly in response to focal demyelinating lesions compared with wild-type animals. The lack of myelin repair was reflected in decreased expression of MBP and proteolipid protein and a reduction in the total number of myelinated axons in the lesion. The number of CC1+ cells in the lesion sites was significantly reduced in Cdk5 cKO compared with wild-type animals although the total number of oligodendrocyte lineage cells (Olig2+ cells) was increased, suggesting that Cdk5 loss perturbs the transition of early OL lineage cell into mature OL and subsequent remyelination. The failure of remyelination in Cdk5 cKO animals was associated with a reduction in signaling through the Akt pathway and an enhancement of Gsk-3β signaling pathways. Together, these data suggest that Cdk5 is critical in regulating the transition of adult oligodendrocyte precursor cells to mature OLs that is essential for myelin repair in adult CNS. PMID:25080600

  14. Tissue damage drives co-localization of NF-κB, Smad3, and Nrf2 to direct Rev-erb sensitive wound repair in mouse macrophages

    PubMed Central

    Eichenfield, Dawn Z; Troutman, Ty Dale; Link, Verena M; Lam, Michael T; Cho, Han; Gosselin, David; Spann, Nathanael J; Lesch, Hanna P; Tao, Jenhan; Muto, Jun; Gallo, Richard L; Evans, Ronald M; Glass, Christopher K

    2016-01-01

    Although macrophages can be polarized to distinct phenotypes in vitro with individual ligands, in vivo they encounter multiple signals that control their varied functions in homeostasis, immunity, and disease. Here, we identify roles of Rev-erb nuclear receptors in regulating responses of mouse macrophages to complex tissue damage signals and wound repair. Rather than reinforcing a specific program of macrophage polarization, Rev-erbs repress subsets of genes that are activated by TLR ligands, IL4, TGFβ, and damage-associated molecular patterns (DAMPS). Unexpectedly, a complex damage signal promotes co-localization of NF-κB, Smad3, and Nrf2 at Rev-erb-sensitive enhancers and drives expression of genes characteristic of multiple polarization states in the same cells. Rev-erb-sensitive enhancers thereby integrate multiple damage-activated signaling pathways to promote a wound repair phenotype. DOI: http://dx.doi.org/10.7554/eLife.13024.001 PMID:27462873

  15. All-trans retinoic acid (RA) stimulates events in organ-cultured human skin that underlie repair. Adult skin from sun-protected and sun-exposed sites responds in an identical manner to RA while neonatal foreskin responds differently.

    PubMed Central

    Varani, J; Perone, P; Griffiths, C E; Inman, D R; Fligiel, S E; Voorhees, J J

    1994-01-01

    Adult human skin from a sun-protected site (hip) and from a sun-exposed site (forearm) was maintained in organ culture for 12 d in the presence of a serum-free, growth factor-free basal medium. Cultures were incubated under conditions optimized for keratinocyte growth (i.e., in 0.15 mM extracellular Ca2+) or for fibroblast growth (i.e., in 1.4 mM extracellular Ca2+). Treatment with all-trans retinoic acid (RA) induced histological changes in the organ-cultured skin under both conditions which were similar to the changes seen in intact skin after topical application. These included expansion of the viable portion of the epidermis and activation of cells in the dermis. In sun-damaged skin samples, which were characterized by destruction of normal connective tissue elements and presence of thick, dark-staining elastotic fibers, a zone of healthy connective tissue could be seen immediately below the dermo-epidermal junction. This zone was more prominent in RA-treated organ cultures than in matched controls. Associated with these histological changes was an increase in overall protein and extracellular matrix synthesis. In concomitant studies, it was found that RA treatment enhanced survival and proliferation of adult keratinocytes and adult dermal fibroblasts under both low- and high-Ca2+ conditions. In all of these assays, responses of sun-protected and sun-exposed skin were identical. In contrast, responses of neonatal foreskin to RA were similar to those of adult skin in the presence of low-Ca2+ culture medium, but under conditions of high extracellular Ca2+ RA provided little or no additional stimulus. Together these studies suggest that the ability of RA to enhance repair of sun-damaged skin (documented in previous studies) may reflect its ability to influence the behavior of skin in a manner that is age dependent but independent of sun-exposure status. Images PMID:7962521

  16. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides

    PubMed Central

    Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two– polyR and Trans – that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael’s addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues. PMID:25894337

  17. Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner

    PubMed Central

    Kolahgar, Golnar; Suijkerbuijk, Saskia J.E.; Kucinski, Iwo; Poirier, Enzo Z.; Mansour, Sarah; Simons, Benjamin D.; Piddini, Eugenia

    2015-01-01

    Summary Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization. Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute−/+ cells in response to chronic JNK stress signaling. PMID:26212135

  18. Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.

    PubMed

    Kolahgar, Golnar; Suijkerbuijk, Saskia J E; Kucinski, Iwo; Poirier, Enzo Z; Mansour, Sarah; Simons, Benjamin D; Piddini, Eugenia

    2015-08-10

    Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization. Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute(-/+) cells in response to chronic JNK stress signaling. PMID:26212135

  19. Cardiac progenitor cells for heart repair

    PubMed Central

    Le, TYL; Chong, JJH

    2016-01-01

    Stem cell therapy is being investigated as an innovative and promising strategy to restore cardiac function in patients with heart failure. Several stem cell populations, including adult (multipotent) stem cells from developed organs and tissues, have been tested for cardiac repair with encouraging clinical and pre-clinical results. The heart has been traditionally considered a post-mitotic organ, however, this view has recently changed with the identification of stem/progenitor cells residing within the adult heart. Given their cardiac developmental origins, these endogenous cardiac progenitor cells (CPCs) may represent better candidates for cardiac cell therapy compared with stem cells from other organs such as the bone marrow and adipose tissue. This brief review will outline current research into CPC populations and their cardiac repair/regenerative potential. PMID:27551540

  20. Low-intensity red and infrared lasers affect mRNA expression of DNA nucleotide excision repair in skin and muscle tissue.

    PubMed

    Sergio, Luiz Philippe S; Campos, Vera Maria A; Vicentini, Solange C; Mencalha, Andre Luiz; de Paoli, Flavia; Fonseca, Adenilson S

    2016-04-01

    Lasers emit light beams with specific characteristics, in which wavelength, frequency, power, fluence, and emission mode properties determine the photophysical, photochemical, and photobiological responses. Low-intensity lasers could induce free radical generation in biological tissues and cause alterations in macromolecules, such as DNA. Thus, the aim of this work was to evaluate excision repair cross-complementing group 1 (ERCC1) and excision repair cross-complementing group 2 (ERCC2) messenger RNA (mRNA) expression in biological tissues exposed to low-intensity lasers. Wistar rat (n = 28, 4 for each group) skin and muscle were exposed to low-intensity red (660 nm) and near-infrared (880 nm) lasers at different fluences (25, 50, and 100 J/cm(2)), and samples of these tissues were withdrawn for RNA extraction, cDNA synthesis, and gene expression evaluation by quantitative polymerase chain reaction. Laser exposure was in continuous wave and power of 100 mW. Data show that ERCC1 and ERCC2 mRNA expressions decrease in skin (p < 0.001) exposed to near-infrared laser, but increase in muscle tissue (p < 0.001). ERCC1 mRNA expression does not alter (p > 0.05), but ERCC2 mRNA expression decreases in skin (p < 0.001) and increases in muscle tissue (p < 0.001) exposed to red laser. Our results show that ERCC1 and ERCC2 mRNA expression is differently altered in skin and muscle tissue exposed to low-intensity lasers depending on wavelengths and fluences used in therapeutic protocols. PMID:26796702

  1. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats.

    PubMed

    Xiao, Bo; Zanoun, Rami R; Carvell, George E; Simons, Daniel J; Washington, Kia M

    2016-03-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures-notably evoked firing rates-closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury. PMID:26792886

  2. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    PubMed

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  3. High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells.

    PubMed

    Palmon, Aaron; David, Ran; Neumann, Yoav; Stiubea-Cohen, Raluca; Krief, Guy; Aframian, Doron J

    2012-02-01

    Isolation of highly pure specific cell types is crucial for successful adult stem cell-based therapy. As the number of such cells in adult tissue is low, an extremely efficient method is needed for their isolation. Here, we describe cell-separation methodologies based on magnetic-affinity cell sorting (MACS) MicroBeads with monoclonal antibodies against specific membrane proteins conjugated to superparamagnetic particles. Cells labeled with MACS MicroBeads are retained in a magnetic field within a MACS column placed in a MACS separator, allowing fast and efficient separation. Both positively labeled and non-labeled fractions can be used directly for downstream applications as the separated cell fractions remain viable with no functional impairment. As immunomagnetic separation depends on the interaction between a cell's membrane and the magnetically labeled antibody, separation of specific cells originating from solid tissues is more complex and demands a cell-dissociating pretreatment. In this paper, we detail the use of immunomagnetic separation for the purpose of regenerating damaged salivary gland (SG) function in animal and human models of irradiated head and neck cancer. Each year 500,000 new cases of head and neck cancer occur worldwide. Most of these patients lose SG function following irradiation therapy. SGs contain integrin α6β1-expressing epithelial stem cells. We hypothesized that these cells can be isolated, multiplied in culture and auto-implanted into the irradiated SGs to regenerate damaged SG function. PMID:22019721

  4. Cross-leg repair of large soft-tissue defects in distal sites of the feet by distally based neuro-fasciocutaneous flaps with perforating vessels.

    PubMed

    Wang, Z Q; Cao, Y L; Huang, Y F; Liu, D Q; Li, X F

    2014-01-01

    The objective of this study was to introduce a method for repairing large soft-tissue defects on the foot. Distally based neuro-fasciocutaneous flaps with perforating vessels were designed along the saphenous and sural neurovascular axes. The cutaneous perforating branches of the major arteries of the lower extremities were used as pedicles, which provided a rotation arc for the cross-leg flap to cover the large-sized soft-tissue defects on the foot. We transferred 6 neurocutaneous vascular axial flaps, including 4 saphenous neurocutaneous axial flaps (ranging from 25 x 13 to 17 x 9 cm in area) with posterior tibial perforators as the pedicle, and 2 sural neurocutaneous axial flaps (ranging from 29 x 12 to 18 x 7 cm in area) supplied by the perforating branches of the peroneal vessels. These 6 cases of neuro-fasciocutaneous flaps survived with satisfactory cosmetic appearances and functional results on follow-up at 8 to 17 months post-surgery. Placing a distally based neuro-fasciocutaneous cross-leg flap with perforating vessels is an effective method for repairing large-sized soft-tissue defects on the foot. PMID:25117303

  5. Effects of In Vitro Low Oxygen Tension Preconditioning of Adipose Stromal Cells on Their In Vivo Chondrogenic Potential: Application in Cartilage Tissue Repair

    PubMed Central

    Gauthier, Olivier; Lesoeur, Julie; Sourice, Sophie; Masson, Martial; Fellah, Borhane Hakim; Geffroy, Olivier; Lallemand, Elodie; Weiss, Pierre

    2013-01-01

    Purpose Multipotent stromal cell (MSC)-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair. Methods MSC from rabbit or human adipose stromal cells (ASC) were preconditioned in vitro in control or chondrogenic (ITS and TGF-β) medium and in 21 or 5% O2. Chondrogenic commitment was monitored by measuring COL2A1 and ACAN expression (real-time PCR). Preconditioned rabbit and human ASC were then incorporated into an Si-HPMC hydrogel and injected (i) into rabbit articular cartilage defects for 18 weeks or (ii) subcutaneously into nude mice for five weeks. The newly formed tissue was qualitatively and quantitatively evaluated by cartilage-specific immunohistological staining and scoring. The phenotype of ASC cultured in a monolayer or within Si-HPMC in control or chondrogenic medium and in 21 or 5% O2 was finally evaluated using real-time PCR. Results/Conclusions 5% O2 increased the in vitro expression of chondrogenic markers in ASC cultured in induction medium. Cells implanted within Si-HPMC hydrogel and preconditioned in chondrogenic medium formed a cartilaginous tissue, regardless of the level of oxygen. In addition, the 3D in vitro culture of ASC within Si-HPMC hydrogel was found to reinforce the pro-chondrogenic effects of the induction medium and 5% O2. These data together indicate that although 5% O2 enhances the in vitro chondrogenic differentiation of ASC, it does not enhance their in vivo chondrogenesis. These results also highlight the in vivo chondrogenic potential of ASC and their potential value in cartilage repair. PMID:23638053

  6. Selective expression of prion protein in peripheral tissues of the adult mouse.

    PubMed

    Ford, M J; Burton, L J; Morris, R J; Hall, S M

    2002-01-01

    The level of expression of normal cellular prion protein, PrP(c) (cellular prion protein), controls both the rate and the route of neuroinvasive infection, from peripheral entry portal to the CNS. Paradoxically, an overview of the distribution of PrP(c) within tissues outside the CNS is lacking. We have used novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue (in order to optimise immunohistochemical labelling of this conformationally labile protein), in combination with in situ hybridisation, to examine the expression of PrP(c) in peripheral tissues of the adult mouse. We found that although prion protein is expressed in many tissues, it is expressed at high levels only in discrete subpopulations of cells. Prominent amongst these are elements of the "hardwired neuroimmune network" that integrate the body's immune defence and neuroendocrine systems under CNS control. These prion protein-expressing elements include small diameter afferent nerves in the skin and the lamina propria of the aerodigestive tract, sympathetic ganglia and nerves, antigen presenting and processing cells (both follicular and non-follicular dendritic cells) and sub-populations of lymphocytes particularly in skin, gut- and bronchus-associated lymphoid tissues. Prion protein is also expressed in the parasympathetic and enteric nervous systems, in the dispersed neuroendocrine system, and in peripheral nervous system axons and their associated Schwann cells. This selective expression of cellular prion protein provides a variety of alternative routes for the propagation and transport of prion infection entering from peripheral sites, either naturally (via the aerodigestive tract or abraded skin) or experimentally (by intraperitoneal injection) to the brain. Key regulatory cells that express prion protein, and in particular enteroendocrine cells in the mucosal wall of the gut, and dendritic cells that convey pathogens from epithelial layers to secondary lymphoid

  7. Next Generation Mesenchymal Stem Cell (MSC)–Based Cartilage Repair Using Scaffold-Free Tissue Engineered Constructs Generated with Synovial Mesenchymal Stem Cells

    PubMed Central

    Shimomura, Kazunori; Ando, Wataru; Moriguchi, Yu; Sugita, Norihiko; Yasui, Yukihiko; Koizumi, Kota; Fujie, Hiromichi; Hart, David A.; Yoshikawa, Hideki

    2015-01-01

    Because of its limited healing capacity, treatments for articular cartilage injuries are still challenging. Since the first report by Brittberg, autologous chondrocyte implantation has been extensively studied. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell–based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. This review summarizes latest development of stem cell therapies in cartilage repair with special attention to scaffold-free approaches. PMID:27340513

  8. The reserve-capacity hypothesis: evolutionary origins and modern implications of the trade-off between tumor-suppression and tissue-repair.

    PubMed

    Weinstein, Bret S; Ciszek, Deborah

    2002-05-01

    Antagonistic pleiotropy, the evolutionary theory of senescence, posits that age related somatic decline is the inevitable late-life by-product of adaptations that increase fitness in early life. That concept, coupled with recent findings in oncology and gerontology, provides the foundation for an integrative theory of vertebrate senescence that reconciles aspects of the 'accumulated damage' 'metabolic rate', and 'oxidative stress' models. We hypothesize that (1) in vertebrates, a telomeric fail-safe inhibits tumor formation by limiting cellular proliferation. (2) The same system results in the progressive degradation of tissue function with age. (3) These patterns are manifestations of an evolved antagonistic pleiotropy in which extrinsic causes of mortality favor a species-optimal balance between tumor suppression and tissue repair. (4) With that trade-off as a fundamental constraint, selection adjusts telomere lengths--longer telomeres increasing the capacity for repair, shorter telomeres increasing tumor resistance. (5) In environments where extrinsically induced mortality is frequent, selection against senescence is comparatively weak as few individuals live long enough to suffer a substantial phenotypic decline. The weaker the selection against senescence, the further the optimal balance point moves toward shorter telomeres and increased tumor suppression. The stronger the selection against senescence, the farther the optimal balance point moves toward longer telomeres, increasing the capacity for tissue repair, slowing senescence and elevating tumor risks. (6) In iteroparous organisms selection tends to co-ordinate rates of senescence between tissues, such that no one organ generally limits life-span. A subsidiary hypothesis argues that senescent decline is the combined effect of (1) uncompensated cellular attrition and (2) increasing histological entropy. Entropy increases due to a loss of the intra-tissue positional information that normally regulates cell

  9. Analysis of histone gene expression in adult tissues of the sea urchins Strongylocentrotus purpuratus and Lytechinus pictus: tissue-specific expression of sperm histone genes.

    PubMed Central

    Lieber, T; Weisser, K; Childs, G

    1986-01-01

    We analyzed the histone mRNA population found in several adult tissues of the sea urchin Strongylocentrotus purpuratus and in testis of Lytechinus pictus. Unique species of H1 and H2b mRNAs encoding the sperm-specific histone subtypes can be found exclusively in testis RNA. S. purpuratus contains two distinct testis-specific H1 transcripts, while L. pictus contains one such transcript. Each of these mRNAs is larger than either early or late embryonic H1 mRNAs. Other somatic adult tissues contain transcripts derived from members of the late embryonic H1 histone gene family. S. purpuratus contains one H2b transcript found exclusively in testis, while L. pictus contains two such H2b mRNAs. Similarly, in tissues other than testis, late H2b transcripts were found. While there is no sperm-specific H2a protein, a limited set of late histone H2a genes encoding primarily the H2a-beta subtype is expressed in testis. The majority of the H2a protein found in diploid adult tissues is also the H2a-beta subtype; however, the size of the H2a transcripts differs between testis and other tissues. We conclude that different members of the late H2a gene family are differentially expressed in embryos and adult tissues. We prepared and characterized cDNA clones encoding the sperm-specific H2b protein as well as the H2a-beta protein found in testis. Images PMID:3785204

  10. We Can Work it Out: The Importance of Rupture and Repair Processes in Infancy and Adult Life for Flourishing.

    PubMed

    Morton, Mary

    2016-06-01

    This paper argues that insights into infant emotional development, particularly the capacity to engage with rupture and repair, can be applied to the understanding and promotion of flourishing in later life, individually and socially. Starting with the Queen's visit to the Republic of Ireland as an example of successful social repair after rupture that enables flourishing, the paper goes on to outline some relevant psychological theory that undergirds this. It then considers some of the practical relevance and problems that apply to rupture and repair in the contemporary world, particularly the world of health care, Amidst the inevitable messiness of life, flourishing and growth can only be achieved with the kind of flexibility implied by creating repair in the face of rupture. PMID:26846477

  11. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  12. Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

    PubMed Central

    Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-01-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

  13. The Sequential Tissue Distribution of Duck Tembusu Virus in Adult Ducks

    PubMed Central

    Wu, Li; Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Ding, Leilei; Lin, Yuan; Li, Qimeng; He, Xijun; Chen, Qiusheng; Chen, Hualan

    2014-01-01

    In 2010, a novel Tembusu virus (TMUV) that caused a severe decrease in the egg production of ducks was isolated in southeast China. Given the novelty of this duck pathogen, little information is available regarding its pathogenesis. Here, we systematically investigated the replication kinetics of TMUV PTD2010 in adult male and female ducks. We found that PTD2010 was detectable in most of the parenchymatous organs as well as the oviduct and intestinal tract from days 1 to 7 after inoculation. Viral titers were maintained at high levels for at least 9 days in the spleen, kidney, bursa of Fabricius, brain, and ovary. No virus was detected in any of these organs or tissues at 18 days after inoculation. PTD2010, thus, causes systemic infections in male and female ducks; its replication kinetics show similar patterns in most organs, with the exception of the ovaries and testes. PMID:25215289

  14. Simultaneous repair of bilateral inguinal hernias under local anesthesia.

    PubMed Central

    Amid, P K; Shulman, A G; Lichtenstein, I L

    1996-01-01

    OBJECTIVE: The authors confirm the advantages of simultaneous repair of bilateral inguinal hernias, indicate that it is feasible to perform the procedure under local anesthesia, and suggest that when an open tension-free technique is used, the results are superior to those of laparoscopic repair of bilateral inguinal hernias. SUMMARY BACKGROUND DATA: Between 1971 and 1995, simultaneous repair of bilateral inguinal hernias were performed in 2953 men. Initially, between 1971 and 1984, patients with indirect hernias underwent the traditional tissue approximation repair. Those with direct hernias had the same procedure, with the repair additionally buttressed by a sheet of Marlex mesh (Davol, Inc., Cronston, RI). Between 1984 and 1995, both direct and indirect hernias were repaired using the open tension-free hernioplasty procedure. METHOD: The 2953 patients underwent simultaneous repair of bilateral inguinal hernias under local anesthesia in a private practice setting in general hospitals. RESULTS: In those cases in which the "tension free" technique was used, patients experienced minimal to mild postoperative pain and had a short recovery period, with a recurrence rate of 0.1%. CONCLUSIONS: Uncomplicated bilateral inguinal hernias in adults are best treated simultaneously. It is feasible to perform the operation under local anesthesia, and when an open tension-free repair is used, postoperative pain and recovery periods are equally comparable with those of laparoscopic repair, although the complication and the recurrence rates are significantly less. Images Figure 1. Figure 2. Figure 3. PMID:8604904

  15. Evaluation of five DNA extraction methods for purification of DNA from atherosclerotic tissue and estimation of prevalence of Chlamydia pneumoniae in tissue from a Danish population undergoing vascular repair

    PubMed Central

    Mygind, Tina; Østergaard, Lars; Birkelund, Svend; Lindholt, Jes S; Christiansen, Gunna

    2003-01-01

    Background To date PCR detection of Chlamydia pneumoniae DNA in atherosclerotic lesions from Danish patients has been unsuccessful. To establish whether non-detection was caused by a suboptimal DNA extraction method, we tested five different DNA extraction methods for purification of DNA from atherosclerotic tissue. Results The five different DNA extraction methods were tested on homogenate of atherosclerotic tissue spiked with C. pneumoniae DNA or EB, on pure C. pneumoniae DNA samples and on whole C. pneumoniae EB. Recovery of DNA was measured with a C. pneumoniae-specific quantitative real-time PCR. A DNA extraction method based on DNA-binding to spin columns with a silica-gel membrane (DNeasy Tissue kit) showed the highest recovery rate for the tissue samples and pure DNA samples. However, an automated extraction method based on magnetic glass particles (MagNA Pure) performed best on intact EB and atherosclerotic tissue spiked with EB. The DNeasy Tissue kit and MagNA Pure methods and the highly sensitive real-time PCR were subsequently used on 78 atherosclerotic tissue samples from Danish patients undergoing vascular repair. None of the samples were positive for C. pneumoniae DNA. The atherosclerotic samples were tested for inhibition by spiking with two different, known amounts of C. pneumoniae DNA and no samples showed inhibition. Conclusion As a highly sensitive PCR method and an optimised DNA extraction method were used, non-detection in atherosclerotic tissue from the Danish population was probably not caused by use of inappropriate methods. However, more samples may need to be analysed per patient to be completely certain on this. Possible methodological and epidemiological reasons for non-detection of C. pneumoniae DNA in atherosclerotic tissue from the Danish population are discussed. Further testing of DNA extraction methods is needed as this study has shown considerable intra- and inter-method variation in DNA recovery. PMID:12952556

  16. Predicting visceral adipose tissue by MRI using DXA and anthropometry in adolescents and young adults

    PubMed Central

    Laddu, Deepika R.; Lee, Vinson R.; Blew, Robert M.; Sato, Tetsuya; Lohman, Timothy G.; Going, Scott B.

    2015-01-01

    Objective Accumulation of intra-abdominal (visceral) adipose tissue, independent of total adiposity, is associated with development of metabolic abnormalities such as insulin resistance and type-2 diabetes in children and adults. The objective of this study was to develop prediction equations for estimating visceral adiposity (VAT) measured by magnetic resonance imaging (MRI) using anthropometric variables and measures of abdominal fat mass from DXA in adolescents and young adults. Methods Cross-sectional data was collected from a multiethnic population of seventy males and females, aged 12–25 years, with BMI ranging from 14.5–38.1 kg/m2. Android (AFM; android region as defined by manufacturers instruction) and lumbar L1-L4 regional fat masses were assessed using DXA (GE Lunar Prodigy; GE Lunar Corp, Madison, WI, USA). Criterion measures of intra-abdominal visceral fat were obtained using single-slice MRI (General Electric Signa Model 5x 1.5T) and VAT area was analyzed at the level OF L4–L5. Image analysis was carried out using ZedView 3.1. Results DXA measures of AFM (r=0.76) and L1-L4 (r=0.71) were significantly (P<0.0001) correlated with MRI-measured VAT. DXA AFM, together with gender and weight, explained 62% of the variance in VAT (SEE=10.06 cm2). DXA L1-L4 fat mass with gender explained 54% of the variance in VAT (SEE=11.08 cm2). Addition of the significant interaction, gender × DXA fat mass, improved prediction of VAT from AFM (Radj2=0.61, SEE=10.10cm2) and L1-L4 (Radj2=0.59, SEE=10.39cm2). Conclusion These results demonstrate that VAT is accurately estimated from regional fat masses measured by DXA in adolescents and young adults. PMID:26097436

  17. Combining stem cells and tissue engineering in cardiovascular repair -- a step forward to derivation of novel implants with enhanced function and self-renewal characteristics.

    PubMed

    Cheema, Faisal H; Polvani, Gianluca; Argenziano, Michael; Pesce, Maurizio

    2012-04-01

    The use of stem and progenitor cells in cardiovascular therapy has been proposed as a feasible option to promote repair of tissue damage by ischemia, or to devise definitive artificial tissue replacements (valves, vessels, myocardium) to be surgically implanted in patients. Whereas in other medical branches such as dermatology and ophthalmology the use of ex vivo grown tissues is already accessible to a large degree, the use of bio-artificial implants in cardiovascular surgery is still marginal. This represents a major limitation in cardiovascular medicine at present. In fact, the limited durability and the lack of full compatibility of current implantable devices or tissues prevent a long-term resolution of symptoms and often require re-intervention thereby further increasing the economic burden of the cardiovascular disease. Stem cell technology can be of help to derive tissues with improved physiologic function and permanent durability. Specifically, the intrinsic ability of stem cells to produce tissue-specific "niches", where immature cells are perpetuated while differentiated progenitors are continuously produced, makes them an ideal resource for bioengineering approaches. Furthermore, recent advancements in biocompatible material science, designing of complex artificial scaffolds and generation of animal or human-derived natural substrates have made it feasible to have ex vivo reproduction of complex cell environment interactions - a process necessary to improve stem cells biological activity. This review focuses on current understanding of cardiovascular stem cell biology as well as tissue engineering and explores their interdisciplinary approach. By reviewing the relevant recent patents which have enabled this field to advance, it concentrates on various design substrates and scaffolds that grow stem cells in order to materialize the production of cardiovascular implants with enhanced functional and self-renewal characteristics. PMID:22280334

  18. Meningocele repair

    MedlinePlus

    ... dysraphism repair; Meningomyelocele repair; Neural tube defect repair; Spina bifida repair ... a medical team with experience in children with spina bifida. Your baby will likely have an MRI (magnetic ...

  19. In vivo facial tissue depth for Canadian Mi'kmaq adults: a case study from Nova Scotia, Canada.

    PubMed

    Peckmann, Tanya R; Harris, Mikkel; Huculak, Meaghan; Pringle, Ashleigh; Fournier, Michel

    2015-01-01

    This study examines facial tissue depth in Canadian Mi'kmaq adults. Using ultrasound, measurements were taken at 19 landmarks on the faces of 152 individuals aged 18-75 years old. The relationships between tissue thickness, age, and sex were investigated. A positive linear trend exists between tissue thickness and age for Mi'kmaq males and females at multiple landmarks. Seven landmarks show significant differences in facial tissue depth between males and females aged 18-34 years old; no landmarks show significant differences in facial tissue depth between males and females aged 35-45 years old and 46-55 years old. Significant differences were shown in facial tissue depth between Mi'kmaq and White Americans and Mi'kmaq and African Americans. These data can assist in 3-D facial reconstructions and aid in establishing the identity of unknown Mi'kmaq individuals. PMID:25572085

  20. Cortical activity evoked by an acute painful tissue-damaging stimulus in healthy adult volunteers

    PubMed Central

    Williams, Gemma; Lee, Amy; Meek, Judith; Slater, Rebeccah; Olhede, Sofia; Fitzgerald, Maria

    2013-01-01

    Everyday painful experiences are usually single events accompanied by tissue damage, and yet most experimental studies of cutaneous nociceptive processing in the brain use repeated laser, thermal, or electrical stimulations that do not damage the skin. In this study the nociceptive activity in the brain evoked by tissue-damaging skin lance was analyzed with electroencephalography (EEG) in 20 healthy adult volunteers (13 men and 7 women) aged 21–40 yr. Time-frequency analysis of the evoked activity revealed a distinct late event-related vertex potential (lance event-related potential, LERP) at 100–300 ms consisting of a phase-locked energy increase between 1 and 20 Hz (delta-beta bands). A pairwise comparison between lance and sham control stimulation also revealed a period of ultralate stronger desynchronization after lance in the delta band (1–5 Hz). Skin application of mustard oil before lancing, which sensitizes a subpopulation of nociceptors expressing the cation channel TRPA1, did not affect the ultralate desynchronization but reduced the phase-locked energy increase in delta and beta bands, suggesting a central interaction between different modalities of nociceptive inputs. Verbal descriptor screening of individual pain experience revealed that lance pain is predominantly due to Aδ fiber activation, but when individuals describe lances as C fiber mediated, an ultralate delta band event-related desynchronization occurs in the brain-evoked activity. We conclude that pain evoked by acute tissue damage is associated with distinct Aδ and C fiber-mediated patterns of synchronization and desynchronization of EEG oscillations in the brain. PMID:23427303

  1. Enhancing repair of full-thickness excisional wounds in a murine model: Impact of tissue-engineered biological dressings featuring human differentiated adipocytes.

    PubMed

    Morissette Martin, Pascal; Maux, Amandine; Laterreur, Véronique; Mayrand, Dominique; L Gagné, Valérie; Moulin, Véronique J; Fradette, Julie

    2015-08-01

    Promotion of skin repair for acute or chronic wounds through the use of tissue-engineered products is an active field of research. This study evaluates the effects mediated by tissue-engineered biological dressings containing human in vitro-differentiated adipocytes and adipose-derived stromal cells (ASCs). Re-epithelialization, granulation tissue formation and neovascularization of full-thickness cutaneous wounds were specifically assessed using a murine model featuring a fluorescent epidermis. In comparison with wounds that did not receive an adipocyte-containing biological dressing, treated wounds displayed a slight but significantly faster wound closure based on macroscopic observations over 18 days. Non-invasive imaging of GFP-expressing keratinocytes determined that the kinetics of re-epithelialization were similar for both groups. Treated wounds featured thicker granulation tissues (1.7-fold, P < 0.0001) enriched in collagens (1.3-fold, P < 0.0104). In addition, wound cryosections labeled for detection of CD31-expressing cells indicated a 2.2-fold (P < 0.0002) increased neovascularization for the treated wounds at the time of terminal biopsy. This is in accordance with the secretion of pro-angiogenic factors detected in media conditioned by the dressings. Taken together, these results establish that a new type of engineered substitutes featuring a mixture of adipocytes and ASCs can promote cutaneous healing when applied as temporary dressings, suggesting their potential relevance for chronic wound management studies. PMID:25934321

  2. Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: A cell-adhesive and plasmin-degradable biosynthetic material for tissue repair

    NASA Astrophysics Data System (ADS)

    Halstenberg, Sven

    2002-01-01

    The goal of the research presented in this dissertation was to create a biomimetic artificial material that exhibits functions of extracellular matrix relevant for improved nerve regeneration. Neural adhesion peptides were photoimmobilized on highly crosslinked poly(ethylene glycol)-based substrates that were otherwise non-adhesive. Neurons adhered in two-dimensional patterns for eleven hours, but no neurites extended. To enable neurite extension and nerve regeneration in three dimensions, and to address the need for specifically cell adhesive and cell degradable materials for clinical applications in tissue repair in general, an artificial protein was recombinantly expressed and purified that consisted of a repeating amino acid sequence based on fibrinogen and anti-thrombin III. The recombinant protein contained integrin-binding RGD sites, plasmin degradation sites, heparin binding sites, and six thiol-containing cysteine residues as grafting sites for poly(ethylene glycol) diacrylate via Michael-type conjugate addition. The resulting protein-graft-poly(ethylene glycol)acrylates were crosslinked by photopolymerization to form hydrogels. Although three-dimensional, RGD mediated and serine protease-dependent ingrowth of human fibroblasts into protein-graft-poly(ethylene glycol) hydrogels occurred, only surface neurite outgrowth was observed from chick dorsal root ganglia. Axonal outgrowth depended on the concentration of matrix-bound heparin, suggesting that improved mechanical strength of the hydrogels and possible immobilization of neuroactive factors due to the presence of heparin promoted neurite outgrowth. Together, the above results show that specific biological functions can be harnessed by protein-graft-poly(ethylene glycol) hydrogels to serve as matrices for tissue repair and regeneration. In particular, the two design objectives, specific cell adhesion and degradability by cell-associated proteases, were fulfilled by the material. In the future, this and

  3. Glucocorticoid effect on repair processes in vascular connective tissue. Morphological examination and biochemical studies on collagen RNA and DNA in rabbit aorta.

    PubMed

    Manthorpe, R; Garbarsch, C; Lorenzen, I

    1975-10-01

    Male rabbits were injured by a single mechanical dilatation of the aorta and then injected with prednisone 2 mg/kg saline for 14 days or starved. Morphological studies and biochemical measurements of the collagen metabolism, the content of alpha-amino nitrogen, RNA, DNA, water and fat, and the aorta to serum ratio of 125I-albumin were performed on the intima-media layer of the descending thoracic aorta. Prednisone inhibited the intimal thickening. In the media the infiltration by mononuclear cells, the proliferation and regeneration of the smooth muscle cells and the calcification were reduced. Prednisone caused a decrease in 0.45 M NaCl soluble collagen as well as in the dialysable and non-dialysable 14C-hydroxyproline fractions. The total amount of collagen, elastin and alpha-amino nitrogen was unchanged, whereas the 14C-proline incorporation in the non-dialysable protein fraction was inhibited to a greater extent than the 14C-hydroxyproline synthesis. The findings indicate that prednisone inhibits the biosynthesis of collagen, which is inhibited to a greater extent than the general protein synthesis. Prednisone increased the dialysable to non-dialysable 14C-hydroxyproline ratio consistent with a relative increase in the catabolism of newly synthesized collagen. The aortic content of RNA and DNA was reduced consistent with the inhibition of protein synthesis and cell proliferation. Finally prednisone decreased the aortic content of water when related to the wet weight and increased the aortic content of fat. The aorta to serum ratio of 125I-albumin was not influenced by prednisone. It is concluded that administration of glucocorticoid for 14 days exerts an inhibitory action on the histological reaction to injury as well as on the biosynthesis of collagen of the repair processes in vascular connective tissue. A comparison with the effects of prednisone on undamaged rabbit aorta (Manthorpe et al. 1974) demonstrates that the metabolism of collagen of vascular

  4. A Digital Gene Expression-Based Bovine Gene Atlas Evaluating 92 Adult, Juvenile and Fetal Cattle Tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A comprehensive transcriptome survey, or “Gene Atlas,” provides information essential for a complete understanding of the genomic biology of an organism. Using a digital gene expression approach, we developed a Gene Atlas of RNA abundance in 92 adult, juvenile and fetal cattle tissues. The samples...

  5. Cartilage Repair and Subchondral Bone Remodeling in Response to Focal Lesions in a Mini-Pig Model: Implications for Tissue Engineering

    PubMed Central

    Fisher, Matthew B.; Belkin, Nicole S.; Milby, Andrew H.; Henning, Elizabeth A.; Bostrom, Marc; Kim, Minwook; Pfeifer, Christian; Meloni, Gregory; Dodge, George R.; Burdick, Jason A.; Schaer, Thomas P.; Steinberg, David R.

    2015-01-01

    Objective: Preclinical large animal models are essential for evaluating new tissue engineering (TE) technologies and refining surgical approaches for cartilage repair. Some preclinical animal studies, including the commonly used minipig model, have noted marked remodeling of the subchondral bone. However, the mechanisms underlying this response have not been well characterized. Thus, our objective was to compare in-vivo outcomes of chondral defects with varied injury depths and treatments. Design: Trochlear chondral defects were created in 11 Yucatan minipigs (6 months old). Groups included an untreated partial-thickness defect (PTD), an untreated full-thickness defect (FTD), and FTDs treated with microfracture, autologous cartilage transfer (FTD-ACT), or an acellular hyaluronic acid hydrogel. Six weeks after surgery, micro-computed tomography (μCT) was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. A finite element model (FEM) was developed to assess load transmission. Results: Using μCT, substantial bone remodeling was observed for all FTDs, but not for the PTD group. The best overall histological scores and greatest type II collagen staining was found for the FTD-ACT and PTD groups. The FEM confirmed that only the FTD-ACT group could initially restore appropriate transfer of compressive loads to the underlying bone. Conclusions: The bony remodeling observed in this model system appears to be a biological phenomena and not a result of altered mechanical loading, with the depth of the focal chondral defect (partial vs. full thickness) dictating the bony remodeling response. The type of cartilage injury should be carefully controlled in studies utilizing this model to evaluate TE approaches for cartilage repair. PMID:25318414

  6. Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin

    PubMed Central

    Gardin, Chiara; Vindigni, Vincenzo; Bressan, Eriberto; Ferroni, Letizia; Nalesso, Elisa; Puppa, Alessandro Della; D’Avella, Domenico; Lops, Diego; Pinton, Paolo; Zavan, Barbara

    2011-01-01

    Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype) were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes. PMID:22072917

  7. Facial soft tissue thickness among various vertical facial patterns in adult Pakistani subjects.

    PubMed

    Jeelani, Waqar; Fida, Mubassar; Shaikh, Attiya

    2015-12-01

    Facial reconstruction techniques are used to obtain an approximation of an individual's appearance thus helping identification of unidentified decedents from their dried skeletal remains. Many of these techniques rely on the sets of average facial soft tissue thickness (FST) values at different anatomical landmarks provided by the previous studies. FST is influenced by the age, sex, ethnicity and the body mass index of the individual. Recent literature has shown that the anthropological variations of the skull may also affect FST at certain points. This study was designed to evaluate the effect of such variations in vertical skull morphology on FST as around one third of different population groups have either a long or short facial pattern as compared to the average facial pattern. Moreover, this study also provides a FST database for the adult Pakistani subjects that may have potential implications in the facial reconstruction of the local subjects. A retrospective analysis of 276 lateral cephalograms of adult subjects having normal sagittal facial pattern was performed. Subjects were categorized into three vertical facial patterns (long face=95, average face=102, short face=79) according to the vertical dimensions of the skull and the FST was measured at 11 midline points. To compare the FST between males and females Mann-Whitney U test was used. Kruskal-Wallis test was applied to compare FST among three vertical facial patterns. The results of our study revealed significant differences in FST at nine landmarks between males and females. These sex-based differences were more pronounced in the long and short facial patterns as compared to the average facial pattern. FST at stomion, pogonion, gnathion and menton was significantly greater in the short facial pattern as compared to the long facial pattern in both the sexes. The results of the present study highlight the importance of anthropological analysis of the skull and taking the vertical skeletal dimension

  8. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  9. Adjuvant Radiotherapy for Pediatric and Young Adult Nonrhabdomyosarcoma Soft-Tissue Sarcoma

    SciTech Connect

    Smith, Kristy B.; Indelicato, Daniel J.; Knapik, Jacquelyn A.; Lagmay, Joanne P.; Morris, Christopher; Kirwan, Jessica M.; Zlotecki, Robert A.; Scarborough, Mark T.; Gibbs, C. Parker; Marcus, Robert B.

    2011-09-01

    Purpose: To evaluate the prognostic factors, outcomes, and complications in patients aged {<=}30 years with resectable nonrhabdomyosarcoma soft-tissue sarcoma treated at the University of Florida with radiotherapy (RT) during a 34-year period. Methods and Materials: A total of 95 pediatric or young adult patients with nonrhabdomyosarcoma soft-tissue sarcoma were treated with curative intent with surgery and RT at the University of Florida between 1973 and 2007. The most common histologic tumor subtypes were synovial sarcoma in 22 patients, malignant fibrous histiocytoma in 19, and malignant peripheral nerve sheath tumor in 11 patients. The mean age at RT was 22 years (range, 6-30). Of the 95 patients, 73 had high-grade tumors; 45 had undergone preoperative RT and 50 postoperative RT. The prognostic factors for survival, local recurrence, and distant recurrence were analyzed. Results: The median follow-up was 7.2 years (range, 0.4-30.5). The actuarial 5-year local control rate was 88%. A microscopically negative margin was associated with superior local control. Although 83% of local recurrence cases initially developed in the absence of metastases, all patients with local failure ultimately died of their disease. The actuarial estimate of 5-year overall survival and disease-free survival was 65% and 63%, respectively. Of all the deaths, 92% were disease related. An early American Joint Committee on Cancer stage, tumor <8 cm, and the absence of neurovascular invasion were associated with superior disease-free survival. The National Cancer Institute Common Toxicity Criteria, version 3, Grade 3-4 treatment complication rate was 9%. No secondary malignancies were observed. Conclusion: In the present large single-institution study, we found positive margins and locally advanced features to be poor prognostic factors for both local progression and survival. The results from the present study have helped to characterize the therapeutic ratio of RT in pediatric and young

  10. Subcutaneous adipose tissue topography (SAT-Top) development in children and young adults.

    PubMed

    Tafeit, Erwin; Möller, Reinhard; Jurimae, Toivo; Sudi, Karl; Wallner, Sandra Johanna

    2007-06-01

    The importance of body composition measurements to elucidate the dynamics of related diseases in pediatrics is gaining recognition. The methods used should not expose subjects to high doses of radiation and require substantial cooperation. The Lipometer is a new optical device that enables the non-invasive, quick and safe determination of the thickness of subcutaneous adipose tissue (SAT) layers (in mm) at any site of the human body. The topographic specification of 15 evenly distributed body sites, which makes it possible to precisely measure subcutaneous body fat distribution, is called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was determined in more than 1000 children and young adults between the ages of 7 and 21. In this paper we describe the SAT-Top development of these subjects through different age groups and the differences between male and female SAT-Top development in each age group. SAT layer profiles (medians of the 15 body sites) for boys and girls in age group 1 (7-9 yrs) show a very similar pattern for both sexes, followed by slightly decreasing SAT layer thicknesses in boys and increasing values in girls in the subsequent age groups. Between age group 3 (11-13 yrs) and age group 7 (19-21 yrs) male and female SAT-Top is significantly different. The discriminating power between male and female SAT-Top was investigated by stepwise discriminant analysis, which provided no significant results for age group 1 (7-9 yrs), about 73% correct classification for age group 2 (9-11 yrs) and 3 (11-13 yrs), 83% for age group 4 (13-15 yrs), and about 91-93% for the following age groups (15-21 yrs). It is known that SAT development is the same in both sexes until puberty, when girls gain relatively more fat mass than boys to reach a higher body-fat percentage as adults. This paper presents a precise description of SAT development in boys and girls from childhood to adolescence, which provides a basis for further investigations. PMID:17847915

  11. Anti-inflammatory/tissue repair macrophages enhance the cartilage-forming capacity of human bone marrow-derived mesenchymal stromal cells.

    PubMed

    Sesia, Sergio B; Duhr, Ralph; Medeiros da Cunha, Carolina; Todorov, Atanas; Schaeren, Stefan; Padovan, Elisabetta; Spagnoli, Giulio; Martin, Ivan; Barbero, Andrea

    2015-06-01

    Macrophages are key players in healing processes. However, little is known on their capacity to modulate the differentiation potential of mesenchymal stem/stromal cells (MSC). Here we investigated whether macrophages (Mf) with, respectively, pro-inflammatory and tissue-remodeling traits differentially modulate chondrogenesis of bone marrow derived-MSC (BM-MSC). We demonstrated that coculture in collagen scaffolds of BM-MSC with Mf derived from monocytes polarized with M-CSF (M-Mf), but not with GM-CSF (GM-Mf) resulted in significantly higher glycosaminoglycan (GAG) content than what would be expected from an equal number of BM-MSC alone (defined as chondro-induction). Moreover, type II collagen was expressed at significantly higher levels in BM-MSC/M-Mf as compared to BM-MSC/GM-Mf constructs, while type X collagen expression was unaffected. In order to understand the possible cellular mechanism accounting for chondro-induction, developing monoculture and coculture tissues were digested and the properties of the isolated BM-MSC analysed. We observed that as compared to monocultures, in coculture with M-Mf, BM-MSC decreased less markedly in number and exhibited higher clonogenic and chondrogenic capacity. Despite their chondro-inductive effect in vitro, M-Mf did not modulate the cartilage tissue maturation in subcutaneous pockets of nude mice, as evidenced by similar accumulation of type X collagen and calcified tissue. Our results demonstrate that coculture of BM-MSC with M-Mf results in synergistic cartilage tissue formation in vitro. Such effect seems to result from the survival of BM-MSC with high chondrogenic capacity. Studies in an orthotopic in vivo model are necessary to assess the clinical relevance of our findings in the context of cartilage repair. PMID:25413299

  12. Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging.

    PubMed

    Yu, Jiao; Takanari, Keisuke; Hong, Yi; Lee, Kee-Won; Amoroso, Nicholas J; Wang, Yadong; Wagner, William R; Kim, Kang

    2013-04-01

    The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice. PMID:23347836

  13. Non-invasive Characterization of Polyurethane-based Tissue Constructs in a Rat Abdominal Repair Model Using High Frequency Ultrasound Elasticity Imaging

    PubMed Central

    Yu, Jiao; Takanari, Keisuke; Hong, Yi; Lee, Kee-Won; Amoroso, Nicholas J.; Wang, Yadong; Wagner, William R.; Kim, Kang

    2013-01-01

    The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice. PMID:23347836

  14. Effects of Runx2 genetic engineering and in vitro maturation of tissue-engineered constructs on the repair of critical size bone defects.

    PubMed

    Byers, Benjamin A; Guldberg, Robert E; Hutmacher, Dietmar W; García, Andrés J

    2006-03-01

    Genetic and tissue engineering strategies are being pursued to address the clinical limitations of current bone grafting materials. Based on our previous work demonstrating that overexpression of the Runx2 osteoblastic transcription factor and in vitro construct maturation synergistically enhanced in vivo mineralization in an ectopic site (Byers et al., Tissue Eng 2004;10:1757-1766), we examined the effects of these two parameters on the repair of critical size bone defects. Primary rat bone marrow stromal cells transduced with Runx2 or control (no Runx2 insert) retroviral vector were seeded onto 3D fused deposition-modeled polycaprolactone scaffolds. Runx2-modified cells produced biologically-equivalent mineralized matrices at nearly 2-fold higher rates than control cells. Constructs cultured in vitro for 1 day (immature) or 21 days (mineralized) were subsequently implanted into critical size calvaria defects in syngeneic rats, and bone healing was analyzed by micro-CT and histomorphometry at 28 days. Runx2-modified and control constructs precultured for 1 day healed to a greater extent than defects receiving no implant. Cell-free scaffolds yielded equivalent levels of bone formation as constructs precultured for 1 day. Interestingly, defects treated with control cell-seeded constructs precultured for 21 days exhibited low bone formation compared to other construct treatments, and repair was comparable to empty defects. In contrast, Runx2-modified constructs precultured for 21 days contained twice as much bone as control constructs precultured for 21 days and equivalent levels of new bone as cell-free and 1 day precultured constructs. These results demonstrate interplay between Runx2 genetically-modified cells and in vitro construct maturation in bone healing responses. PMID:16287095

  15. Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

    PubMed Central

    Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

    2013-01-01

    Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

  16. Medulloblastoma with soft-tissue and skeletal metastases in an adult: A case report

    PubMed Central

    GENG, DIANZHONG; SONG, XIAOHUA; LIU, JING; YU, ZESHUN; NING, FANGLING

    2015-01-01

    Medulloblastoma (MB) is a highly malignant primary brain tumor, which occurs in the cerebellum or posterior cranial fossa. MB is most commonly identified in children <10 years of age. The disease is rare in adults, affecting patients aged between 30 and 50 years of age, with an incidence of 0.5 cases per 1,000,000 individuals. Extraneural metastases are reported in 7–10% of cases, most commonly involving the bones and more rarely involving the lymph nodes, visceral organs and bone marrow. The current study presents the case of a 36-year-old male who underwent a gross total resection followed by radiation therapy to the craniospinal axis for the treatment of MB. The patient subsequently developed widespread metastasis, which involved the soft tissue of the occipital bone. Subsequently, the patient was administered palliative radiotherapy and initially exhibited a good clinical response. However, the patient succumbed at 18 months post-diagnosis due to dissemination of the disease. The literature on the extraneural metastasis of MB is also reviewed in the current study. PMID:26622837

  17. A mystery unraveled: nontumorigenic pluripotent stem cells in human adult tissues

    PubMed Central

    Simerman, Ariel A; Perone, Marcelo J; Gimeno, María L; Dumesic, Daniel A; Chazenbalk, Gregorio D

    2014-01-01

    Introduction: Embryonic stem cells and induced pluripotent stem cells have emerged as the gold standard of pluripotent stem cells and the class of stem cell with the highest potential for contribution to regenerative and therapeutic application; however, their translational use is often impeded by teratoma formation, commonly associated with pluripotency. We discuss a population of nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress Enduring (Muse) cells, which offer an innovative and exciting avenue of exploration for the potential treatment of various human diseases. Areas covered: This review discusses the origin of Muse cells, describes in detail their various unique characteristics, and considers future avenues of their application and investigation with respect to what is currently known of adult pluripotent stem cells in scientific literature. We begin by defining cell potency, then discuss both mesenchymal and various reported populations of pluripotent stem cells, and finally delve into Muse cells and the characteristics that set them apart from their contemporaries. Expert opinion: Muse cells derived from adipose tissue (Muse-AT) are efficiently, routinely and painlessly isolated from human lipoaspirate material, exhibit tripoblastic differentiation both spontaneously and under media-specific induction, and do not form teratomas. We describe qualities specific to Muse-AT cells and their potential impact on the field of regenerative medicine and cell therapy. PMID:24745973

  18. Adjuvant Chemotherapy Following Complete Resection of Soft Tissue Sarcoma in Adults: A Clinical Practice Guideline

    PubMed Central

    Bramwell, Vivien H. C.; Bell, Robert; Davis, Aileen M.; Charette, Manya L.; The members of the cancer care Ontario practice guidelines initiative sarcoma disease site group

    2002-01-01

    Purpose. To review the literature and make recommendations for the use of anthracycline-based adjuvant chemotherapy in adult patients with soft tissue sarcoma (STS). Patients. The recommendations apply to patients >15 years old with completely resected STS. Methods. A systematic overview of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline. Results. Four meta-analyses and 17 randomized clinical trials comparing anthracycline-based adjuvant chemotherapy versus observation were reviewed. The Sarcoma Meta-Analysis Collaboration (SMAC) was the best analysis because it assessed individual patient data and had the longest follow-up. The results of the SMAC meta-analysis together with data from more recently published randomized trials, as well as our analysis of the toxicity and compliance data, are incorporated in this systematic review. Discussion. It is reasonable to consider anthracycline-based adjuvant chemotherapy in patients who have had removal of a sarcoma with features predicting a high likelihood of relapse (deep location, size >5 cm, high histological grade). Although the benefits of adjuvant chemotherapy are most apparent in patients with extremity sarcomas, patients with high-risk tumours at other sites should also be considered for such therapy. PMID:18521341

  19. Comparative microarray analyses of adult female midgut tissues from feeding Rhipicephalus species.

    PubMed

    van Zyl, Willem A; Stutzer, Christian; Olivier, Nicholas A; Maritz-Olivier, Christine

    2015-02-01

    The cattle tick, Rhipicephalus microplus, has a debilitating effect on the livestock industry worldwide, owing to its being a vector of the causative agents of bovine babesiosis and anaplasmosis. In South Africa, co-infestation with R. microplus and R. decoloratus, a common vector species on local livestock, occurs widely in the northern and eastern parts of the country. An alternative to chemical control methods is sought in the form of a tick vaccine to control these tick species. However, sequence information and transcriptional data for R. decoloratus is currently lacking. Therefore, this study aimed at identifying genes that are shared between midgut tissues of feeding adult female R. microplus and R. decoloratus ticks. In this regard, a custom oligonucleotide microarray comprising of 13,477 R. microplus sequences was used for transcriptional profiling and 2476 genes were found to be shared between these Rhipicephalus species. In addition, 136 transcripts were found to be more abundantly expressed in R. decoloratus and 1084 in R. microplus. Chi-square analysis revealed that genes involved in lipid transport and metabolism are significantly overrepresented in R. microplus and R. decoloratus. This study is the first transcriptional profiling of R. decoloratus and is an additional resource that can be evaluated further in future studies for possible tick control. PMID:25448423

  20. Transposable elements and their KRAB-ZFP controllers regulate gene expression in adult tissues

    PubMed Central

    Ecco, Gabriela; Cassano, Marco; Kauzlaric, Annamaria; Duc, Julien; Coluccio, Andrea; Offner, Sandra; Imbeault, Michaël; Rowe, Helen M.; Turelli, Priscilla; Trono, Didier

    2016-01-01

    Summary KRAB-containing zinc finger proteins (KRAB-ZFPs) are early embryonic controllers of transposable elements (TEs), which they repress with their cofactor KAP1 through histone and DNA methylation, a process thought to result in irreversible silencing. Using a target-centered functional screen, we matched murine TEs with their cognate KRAB-ZFP. We found the paralogs ZFP932 and Gm15446 to bind overlapping but distinguishable subsets of ERVK (endogenous retrovirus K), to repress these elements in embryonic stem cells, and to regulate secondarily the expression of neighboring genes. Most importantly, we uncovered that these KRAB-ZFPs and KAP1 control TEs in adult tissues, in cell culture and in vivo, where they partner up to modulate cellular genes. Therefore, TEs and KRAB-ZFPs establish transcriptional networks that regulate not only development but probably many physiological events. Given the high degree of species-specificity of TEs and KRAB-ZFPs, these results have important implications for understanding the biology of higher vertebrates, including humans. PMID:27003935

  1. CD95/CD95L-mediated apoptosis of the hepatic stellate cell. A mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair.

    PubMed Central

    Saile, B.; Knittel, T.; Matthes, N.; Schott, P.; Ramadori, G.

    1997-01-01

    During liver tissue repair, hepatic stellate cells (HSC), a pericyte-like mesenchymal liver cell population, transform from a "quiescent" status ("resting" HSC) into myofibroblast-like cells ("activated" HSC) with the latter representing the principle matrix synthesizing cell of the liver. Presently, the mechanisms that terminate HSC cell proliferation when tissue repair is concluded are poorly understood. Controlled cell death known as apoptosis could be a mechanism underlying this phenomenon. Therefore, apoptosis and its regulation were studied in HSC using an in vitro and in vivo approach. Spontaneous apoptosis became detectable in parallel with HSC activation because resting cells (2 days after isolation) displayed no sign of apoptosis, whereas apoptosis was present in 8% (+/- 5%) of "transitional" cells (day 4) and in 18% (+/- 8%) of fully activated cells (day 7). Both CD95 (APO-1/Fas) and CD95L (APO-1-/Fas-ligand) became increasingly expressed during the course of activation. Apoptosis could be fully blocked by CD95-blocking antibodies in normal cells and HSC already entering the apoptotic cycle. Using CD95-activating antibodies, transition of more than 95% cells into apoptosis was evident at each activation step. The apoptosis-regulating proteins Bcl-2 and p53 could not be detected in resting cells but were found in increasing amounts at days 4 and 7 of cultivation. Whereas p53 expression was induced by the CD95-activating antibody, no change was inducible in Bcl-2 expression. The Bcl-2-related protein bax could be found at days 2 and 4 in similar expression, was considerably up-regulated at day 7, but was not regulated by CD95-agonistic antibodies. In vivo, acute tissue damage was first accompanied by activation and proliferation of HSC displaying no sign of apoptosis. In the recovery phase, apoptotic HSC were detectable in parallel to a reduction in the total number of HSC present in the liver tissue. The data demonstrate that apoptosis becomes detectable

  2. Directing and Potentiating Stem Cell-Mediated Angiogenesis and Tissue Repair by Cell Surface E-Selectin Coating

    PubMed Central

    Kovalski, Letícia; Wang, Bo; Tian, Runxia; Castilla, Diego M.; Dikici, Emre; Perez, Victor L.; Deo, Sapna; Daunert, Sylvia; Velazquez, Omaida C.

    2016-01-01

    Stem cell therapy has emerged as a promising approach for treatment of a number of diseases, including delayed and non-healing wounds. However, targeted systemic delivery of therapeutic cells to the dysfunctional tissues remains one formidable challenge. Herein, we present a targeted nanocarrier-mediated cell delivery method by coating the surface of the cell to be delivered with dendrimer nanocarriers modified with adhesion molecules. Infused nanocarrier-coated cells reach to destination via recognition and association with the counterpart adhesion molecules highly or selectively expressed on the activated endothelium in diseased tissues. Once anchored on the activated endothelium, nanocarriers-coated transporting cells undergo transendothelial migration, extravasation and homing to the targeted tissues to execute their therapeutic role. We now demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of bone marrow cells (BMC) to cutaneous wound tissues and grafted corneas and its advantages over conventional BMC transplantation in mouse models for wound healing and neovascularization. This versatile platform is suited for targeted systemic delivery of virtually any type of therapeutic cell. PMID:27104647

  3. Directing and Potentiating Stem Cell-Mediated Angiogenesis and Tissue Repair by Cell Surface E-Selectin Coating.

    PubMed

    Liu, Zhao-Jun; Daftarian, Pirouz; Kovalski, Letícia; Wang, Bo; Tian, Runxia; Castilla, Diego M; Dikici, Emre; Perez, Victor L; Deo, Sapna; Daunert, Sylvia; Velazquez, Omaida C

    2016-01-01

    Stem cell therapy has emerged as a promising approach for treatment of a number of diseases, including delayed and non-healing wounds. However, targeted systemic delivery of therapeutic cells to the dysfunctional tissues remains one formidable challenge. Herein, we present a targeted nanocarrier-mediated cell delivery method by coating the surface of the cell to be delivered with dendrimer nanocarriers modified with adhesion molecules. Infused nanocarrier-coated cells reach to destination via recognition and association with the counterpart adhesion molecules highly or selectively expressed on the activated endothelium in diseased tissues. Once anchored on the activated endothelium, nanocarriers-coated transporting cells undergo transendothelial migration, extravasation and homing to the targeted tissues to execute their therapeutic role. We now demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of bone marrow cells (BMC) to cutaneous wound tissues and grafted corneas and its advantages over conventional BMC transplantation in mouse models for wound healing and neovascularization. This versatile platform is suited for targeted systemic delivery of virtually any type of therapeutic cell. PMID:27104647

  4. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    SciTech Connect

    Minamino, Tsutomu; Ito, Yoshiya; Ohkubo, Hirotoki; Hosono, Kanako; Suzuki, Tatsunori; Sato, Takehito; Ae, Takako; Shibuya, Akitaka; Sakagami, Hiroyuki; Narumiya, Shuh; Koizumi, Wasaburo; Majima, Masataka

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  5. DNA repair

    SciTech Connect

    Friedberg, E.C.; Hanawalt, P.C. )

    1988-01-01

    Topics covered in this book included: Eukaryote model systems for DNA repair study; Sensitive detection of DNA lesions and their repair; and Defined DNA sequence probes for analysis of mutagenesis and repair.

  6. Endothelial repair process and its relevance to longitudinal neointimal tissue patterns: comparing histology with in silico modelling

    PubMed Central

    Tahir, Hannan; Bona-Casas, Carles; Narracott, Andrew James; Iqbal, Javaid; Gunn, Julian; Lawford, Patricia; Hoekstra, Alfons G.

    2014-01-01

    Re-establishing a functional endothelium following endovascular treatment is an important factor in arresting neointimal proliferation. In this study, both histology (in vivo) and computational simulations (in silico) are used to evaluate neointimal growth patterns within coronary arteries along the axial direction of the stent. Comparison of the growth configurations in vivo and in silico was undertaken to identify candidate mechanisms for endothelial repair. Stent, lumen and neointimal areas were measured from histological sections obtained from eight right coronary stented porcine arteries. Two re-endothelialization scenarios (endothelial cell (EC) random seeding and EC growth from proximal and distal ends) were implemented in silico to evaluate their influence on the morphology of the simulated lesions. Subject to the assumptions made in the current simulations, comparison between in vivo and in silico results suggests that endothelial growth does not occur from the proximal and distal ends alone, but is more consistent with the assumption of a random seeding process. This may occur either from the patches of endothelium which survive following stent implantation or from attachment of circulating endothelial progenitor cells. PMID:24621816

  7. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection.

    PubMed

    Blériot, Camille; Dupuis, Théo; Jouvion, Grégory; Eberl, Gérard; Disson, Olivier; Lecuit, Marc

    2015-01-20

    Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively. PMID:25577440

  8. Linear rank tests for interval-censored data with application to PCB levels in adipose tissue of transformer repair workers

    SciTech Connect

    Self, S.G.; Grossman, E.A.

    1986-09-01

    Linear rank statistics are described for testing for differences between groups when the data are interval-censored. The statistics are closely related to those described by Prentice for right-censored data. Problems in calculating the statistics are discussed and several approaches to computation including estimation of the efficient rank scores are described. Results from a small simulation study are presented. The methods are applied to data from a study relating tissue levels of PCBs to occupational exposure.

  9. Periodontal repair in dogs: histologic observations of guided tissue regeneration with a prostaglandin E1 analog/methacrylate composite.

    PubMed

    Trombelli, L; Lee, M B; Promsudthi, A; Guglielmoni, P G; Wikesjö, U M

    1999-06-01

    This report describes observations of healing following guided tissue regeneration (GTR) including surgical implantation of the prostaglandin E1 analog misoprostol with calcium-layered methacrylate particles. Critical size, supra-alveolar periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in 4 beagle dogs. Wound management included soaking with a 24 microg/ml misoprostol solution and implantation of the misoprostol/methacrylate composite. One jaw quadrant per animal was prepared for GTR using expanded polytetrafluoroethylene membranes. The gingival flaps were coronally advanced and sutured to submerge the teeth. The tissues covering the surgical sites daily received topical misoprostol in an oral adhesive over the 4-week healing interval. Upon euthanasia, tissue blocks were prepared for histometric analysis of regeneration of alveolar bone and cementum, root resorption and ankylosis. The defect area underneath the membrane and the density of methacrylate particles were recorded for the GTR defects. The methacrylate particles appeared encapsulated in a dense connective tissue without signs of an inflammatory reaction, some in contact to newly formed bone. Alveolar bone regeneration height averaged (+/-SD) 1.2+/-1.0 and 1.0+/-0.6 mm for GTR and non-GTR defects, respectively. Corresponding values for bone regeneration area were 1.3+/-1.0 and 0.7+/-0.5 mm2. Cementum regeneration was confined to the apical aspect of the defects. Small areas of root resorption and ankylosis were observed for all teeth. Bone regeneration area correlated positively to the defect area and negatively to the density of methacrylate particles in the GTR defects. The histologic observations suggest that the methacrylate composite has marginal potential to promote bone and cementum regeneration under provisions for GTR. PMID:10382578

  10. Rapid Fabrication of Living Tissue Models by Collagen Plastic Compression: Understanding Three-Dimensional Cell Matrix Repair In Vitro

    PubMed Central

    Cheema, Umber; Brown, Robert A.

    2013-01-01

    Objective To produce biomimetic collagen scaffolds for tissue modeling and as tissue-engineered implants. Approach Control of collagen fibril material parameters in collagen hydrogel scaffolds by using plastic compression (PC), resulting in direct control of cell proliferation, cell migration, and cell–cell interaction. Results We were able to control the density of collagen in such scaffolds from between 0.2% and 30%, and controllably layer the fibrils in the Z-plane. Cell migration was observed in gels where a gradient of collagen density was present. In these gels, cells preferentially migrated toward the collagen-dense areas. Cell proliferation rates were measurably higher in dense collagen gels. Innovation The use of PC to control material properties of collagen hydrogels results in collagen scaffolds that are biomimetic. These collagen gels reproduce the relevant matrix-mechanical environment in which behavior is more representative of that found in vivo. Conclusion The material properties of native collagen type I gels can be engineered to match those found in tissues in vivo to elicit more biomimetic cell behavior. PMID:24527341

  11. Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue-engineering for spinal cord defect repair in rat fetuses with spina bifida aperta.

    PubMed

    Li, Xiaoshuai; Yuan, Zhengwei; Wei, Xiaowei; Li, Hui; Zhao, Guifeng; Miao, Jiaoning; Wu, Di; Liu, Bo; Cao, Songying; An, Dong; Ma, Wei; Zhang, Henan; Wang, Weilin; Wang, Qiushi; Gu, Hui

    2016-04-01

    Spina bifida aperta are complex congenital malformations resulting from failure of fusion in the spinal neural tube during embryogenesis. Despite surgical repair of the defect, most patients who survive with spina bifida aperta have a multiple system handicap due to neuron deficiency of the defective spinal cord. Tissue engineering has emerged as a novel treatment for replacement of lost tissue. This study evaluated the prenatal surgical approach of transplanting a chitosan-gelatin scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in the healing the defective spinal cord of rat fetuses with retinoic acid induced spina bifida aperta. Scaffold characterisation revealed the porous structure, organic and amorphous content. This biomaterial promoted the adhesion, spreading and in vitro viability of the BMSCs. After transplantation of the scaffold combined with BMSCs, the defective region of spinal cord in rat fetuses with spina bifida aperta at E20 decreased obviously under stereomicroscopy, and the skin defect almost closed in many fetuses. The transplanted BMSCs in chitosan-gelatin scaffold survived, grew and expressed markers of neural stem cells and neurons in the defective spinal cord. In addition, the biomaterial presented high biocompatibility and slow biodegradation in vivo. In conclusion, prenatal transplantation of the scaffold combined with BMSCs could treat spinal cord defect in fetuses with spina bifida aperta by the regeneration of neurons and repairmen of defective region. PMID:26894267

  12. Human Endometrial Mesenchymal Stem Cells Modulate the Tissue Response and Mechanical Behavior of Polyamide Mesh Implants for Pelvic Organ Prolapse Repair

    PubMed Central

    Ulrich, Daniela; Edwards, Sharon Lee; Su, Kai; Tan, Ker Sin; White, Jacinta F.; Ramshaw, John A.M.; Lo, Camden; Rosamilia, Anna; Werkmeister, Jerome A.

    2014-01-01

    Background: Pelvic organ prolapse (POP) is defined as the descent of one or more of the pelvic structures into the vagina and includes uterine, vaginal vault, and anterior or posterior vaginal wall prolapse. The treatment of POP may include implantation of a synthetic mesh. However, the long-term benefit of mesh surgery is controversial due to complications such as mesh exposure or pain. The aim of this study was to use a tissue engineering (TE) approach to assess the in vivo biological and biomechanical behavior of a new gelatin/polyamide mesh, seeded with a novel source of mesenchymal stem cells in a subcutaneous rat model of wound repair. Methods: W5C5-enriched human endometrial mesenchymal stem cells (eMSC) were seeded onto meshes (gelatin-coated polyamide knit) at 100,000 cells/cm2. Meshes, with or without cells were subcutaneously implanted dorsally in immunocompromised rats for 7, 30, 60, and 90 days. Flow cytometry was used to detect DiO labeled cells after explantation. Immunohistochemical assessment of foreign body reaction and tissue integration were conducted. Total collagen and the levels of collagens type III and type I were determined. Uniaxial tensiometry was performed on explanted meshes, originally seeded with and without cells, at days 7 and 90. Results: Implanted meshes were well tolerated, with labeled cells detected on the mesh up to 14 days postimplantation. Meshes with cells promoted significantly more neovascularization at 7 days (p<0.05) and attracted fewer macrophages at 90 days (p<0.05). Similarly, leukocyte infiltration was significantly lower in the cell-seeded meshes at 90 days (p<0.05). Meshes with cells were generally less stiff than those without cells, after 7 and 90 days implantation. Conclusion: The TE approach used in this study significantly reduced the number of inflammatory cells around the implanted mesh and promoted neovascularization. Seeding with eMSC exerts an anti-inflammatory effect and promotes wound repair with new

  13. Increased BrdU incorporation reflecting DNA repair, neuronal de-differentiation or possible neurogenesis in the adult cochlear nucleus following bilateral cochlear lesions in the rat.

    PubMed

    Zheng, Yiwen; Begum, Shaeza; Zhang, Chu; Fleming, Kirk; Masumura, Chisako; Zhang, Ming; Smith, Paul; Darlington, Cynthia

    2011-05-01

    Neurogenesis is known to occur in response to injury in the brain, for example, as a result of neurodegenerative diseases. However, there have been few investigations into how the brain responds to damage to peripheral sensory nerves, in other areas such as the brainstem. Here, we report that bilateral surgical lesions of the cochlea result in increased incorporation of the DNA replication marker, bromodeoxyuridine (BrdU), in cells of the brainstem cochlear nucleus (CN) of the adult rat, suggesting either cell proliferation or DNA repair. Some of the BrdU-labelled cells colabelled for the mature neuron marker, NeuN and the GABAergic enzyme GAD-65, suggesting the possibility that neurogenesis might have occurred and resulted in the generation of new neurons with a GABAergic phenotype. However, some of the mature neurons also re-expressed immature neuronal intermediate filament and microtuble-associated proteins, without apoptotic neuronal death, which suggests that the colabelling of BrdU with NeuN and GAD-65 may not be a true reflection of neurogenesis, but injury-stimulated neuronal dedifferentiation. These results suggest the possibility that DNA repair, neuronal de-differentiation or possible neurogenesis occurs in the cochlear nucleus, in response to damage to the peripheral auditory system. PMID:21104237

  14. A randomized, double-blind comparison between parecoxib sodium and propacetamol for parenteral postoperative analgesia after inguinal hernia repair in adult patients.

    PubMed

    Beaussier, M; Weickmans, H; Paugam, C; Lavazais, S; Baechle, J P; Goater, P; Buffin, A; Loriferne, J F; Perier, J F; Didelot, J P; Mosbah, A; Said, R; Lienhart, A

    2005-05-01

    The newly injectable cyclooxygenase-2 selective nonsteroidal antiinflammatory drug, parecoxib, has never been compared with propacetamol, a parenteral formulation of acetaminophen. In this prospective, randomized, double-blind, double-dummy study, we randomly assigned 182 patients scheduled for initial inguinal hernia repair under general anesthesia to receive a single injection of 40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after surgery. The study variables were morphine consumption, pain at rest and while coughing, and patient satisfaction throughout the first 12 h postoperatively. For statistical analysis, we used the Student's t-test, chi(2), and covariance analysis. Total morphine consumption did not differ between the two groups. Pain was less intense in the parecoxib group at rest (P = 0.035) but did not differ for pain while coughing. The incidence of side effects was similar. Significantly more patients in the parecoxib group rated their pain management as good or excellent (87% versus 70% in the propacetamol group, P = 0.001). Within the first 12 h after inguinal hernia repair in adult patients, a single injection of parecoxib 40 mg compares favorably with 2 injections of propacetamol 2 g. PMID:15845675

  15. Relationship of articular soft tissue contour and shape to the underlying eminence and slope profile in young adult temporomandibular joints.

    PubMed

    Pullinger, A G; Bibb, C A; Ding, X; Baldioceda, F

    1993-11-01

    This study examined whether the overall shape of the articular soft tissue overlying the posterior slope and articular eminence of the temporal bone could be predicted by the underlying osseous contour in a histologic model of 51 central sagittal sections of young adult temporomandibular joints. Articular soft tissue and bone contours were traced, and osseous landmarks identified on the basis of joint geometry. Soft tissue thickness measurements were made under low power light microscopy. Seven categories of articular soft tissue pattern were identified. The soft tissue uniformly followed the osseous contour in only one (14%). A progressive increase in soft tissue thickness from the middle of the posterior slope to the articular crest was the most common pattern (35%) but did not describe most of the sample that was more asymmetric. Pattern was poorly predicted by the shape and slope of the temporal bone outline or by dental factors that describe anterior guidance and did not relate to disk displacement. The articular soft tissue compensated for flatter eminence slopes and osseous irregularities and maintained an intact surface. This study has clinical implications for radiographic interpretation of disk space, condyle translation pathways, and the integrity of the functional articular surface. PMID:8247507

  16. Preparation and Application of an Innovative Thrombocyte/Leukocyte-Enriched Plasma to Promote Tissue Repair in Chelonians

    PubMed Central

    Di Ianni, Francesco; Merli, Elisa; Burtini, Francesca; Conti, Virna; Pelizzone, Igor; Di Lecce, Rosanna; Parmigiani, Enrico; Squassino, Gian Paolo; Del Bue, Maurizio; Lucarelli, Enrico; Ramoni, Roberto; Grolli, Stefano

    2015-01-01

    Platelet concentrates are widely used in mammalian regenerative medicine to improve tissue healing. Chelonians (Testudines) would benefit from the application of thrombocyte preparations to regenerate damaged tissues, since traumatic injuries are leading causes of morbidity and mortality for both wild-living and domesticated animals. The aim of this study was to establish a protocol that optimized the recovery of the thrombocytes from blood samples and to show the efficacy of thrombocyte-enriched plasma in chelonians. Peripheral blood samples were obtained from Testudo spp. (n = 12) and Trachemys scripta elegans (n = 10). Blood cells were fractionated by sodium diatrizoate-sodium polysucrose density gradient using a two-step centrifugation protocol. Thrombocytes and leukocytes were isolated and resuspended to obtain thrombocyte-leucocyte rich plasma (TLRP). The mean recovery of leukocytes and thrombocytes was 48.9% (±4.0 SEM, n = 22) of the whole blood cell content. No statistically significant difference was observed between blood samples collected from different turtle species. The ability of TLRP to form a gel was evaluated by adding variable concentrations of calcium gluconate at room temperature and at 37°C. A reliable and consistent clotting of the TLRP was obtained in glass tubes and dishes by adding 5-20% v/v of a 100 mg/ml solution of calcium gluconate. Furthermore, in order to test the clinical efficacy of TLRP, a preliminary evaluation was performed on four turtles (Testudo spp.) with traumatic injuries. In all the four animals, a successful clinical outcome was observed. The results demonstrated that a thrombocyte-enriched plasma, comparable to mammalian platelet rich plasma, can be prepared from chelonian blood samples. Furthermore, although the low number of cases presented does not allow definitive conclusions from a clinical point of view, their outcome suggests that TLRP application could be further investigated to improve the healing process of

  17. Proteomic Analysis Profile of Engineered Articular Cartilage with Chondrogenic Differentiated Adipose Tissue-Derived Stem Cells Loaded Polyglycolic Acid Mesh for Weight-Bearing Area Defect Repair

    PubMed Central

    Gong, Lunli; Zhou, Xiao; Wu, Yaohao; Zhang, Yun; Wang, Chen; Zhou, Heng; Guo, Fangfang

    2014-01-01

    The present study was designed to investigate the possibility of full-thickness defects repair in porcine articular cartilage (AC) weight-bearing area using chondrogenic differentiated autologous adipose-derived stem cells (ASCs) with a follow-up of 3 and 6 months, which is successive to our previous study on nonweight-bearing area. The isolated ASCs were seeded onto the phosphoglycerate/polylactic acid (PGA/PLA) with chondrogenic induction in vitro for 2 weeks as the experimental group prior to implantation in porcine AC defects (8 mm in diameter, deep to subchondral bone), with PGA/PLA only as control. With follow-up time being 3 and 6 months, both neo-cartilages of postimplantation integrated well with the neighboring normal cartilage and subchondral bone histologically in experimental group, whereas only fibrous tissue in control group. Immunohistochemical and toluidine blue staining confirmed similar distribution of COL II and glycosaminoglycan in the regenerated cartilage to the native one. A vivid remolding process with repair time was also witnessed in the neo-cartilage as the compressive modulus significantly increased from 70% of the normal cartilage at 3 months to nearly 90% at 6 months, which is similar to our former research. Nevertheless, differences of the regenerated cartilages still could be detected from the native one. Meanwhile, the exact mechanism involved in chondrogenic differentiation from ASCs seeded on PGA/PLA is still unknown. Therefore, proteome is resorted leading to 43 proteins differentially identified from 20 chosen two-dimensional spots, which do help us further our research on some committed factors. In conclusion, the comparison via proteome provided a thorough understanding of mechanisms implicating ASC differentiation toward chondrocytes, which is further substantiated by the present study as a perfect supplement to the former one in nonweight-bearing area. PMID:24044689

  18. Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives.

    PubMed

    Raftery, Rosanne M; Walsh, David P; Castaño, Irene Mencía; Heise, Andreas; Duffy, Garry P; Cryan, Sally-Ann; O'Brien, Fergal J

    2016-07-01

    As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy. Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the defect site, causing off-target side effects and cytotoxicity. Gene therapy involves the introduction of foreign genes into a cell in order to exert an effect; either replacing a missing gene or modulating expression of a protein. State of the art gene therapy also encompasses manipulation of the transcriptome by harnessing RNA interference (RNAi) therapy. The delivery of nucleic acid nanomedicines on biomaterial scaffolds - gene-activated scaffolds -has shown potential for use in a variety of tissue engineering applications, but as of yet, have not reached clinical use. The current state of the art in terms of biomaterial scaffolds and delivery vector materials for gene therapy is reviewed, and the limitations of current procedures discussed. Future directions in the clinical translation of gene-activated scaffolds are also considered, with a particular focus on bone and cartilage tissue regeneration. PMID:26840618

  19. The distribution and localization of /sup 127/m tellurium in normal and pathological nervous tissues of young and adult rats

    SciTech Connect

    Duckett, S.

    1982-11-01

    An equal amount (per weight) of /sup 127/m tellurium (Te) was injected IP into weanling and adult rats, some intoxicated with a diet containing Te, others not. The young intoxicated rats presented a segmental demyelination of the sciatic nerve and paralysis of the hind limbs; the adult intoxicated rats did not. Quantitation of 127m Te in nervous and other tissues was done with a gamma counter. Correlative morphological examination of the nervous tissues was done with light and electron microscopy. This study shows that Te crosses the vascular wall without injuring endothelial cells and invades the surrounding sciatic nerve parenchyma following administration of 127m Te to a weanling or adult rat. However, Te damages the endothelium, crosses the vascular wall of endo and perineurial vessels in weanling rats, causes a perivascular oedema, cytoplasmic anomalies in the Schwann cells, destruction of myelin and apparently invades axones--according to autoradiographic studies--following the administration of 127m Te plus the Te-diet. It is concluded that Te penetrates more quickly and in larger amounts the walls of blood vessels in the sciatic nerve of weanling rats intoxicated with Te, than the same nerve in the other weanling and adults rats. Te in the amounts indicated here penetrates the parenchyma of the CNS but apparently does not cause injury.

  20. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  1. Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cholecalciferol is known to be deposited in human adipose tissue, but the distribution of 25-hydroxyvitamin D (25(OH)D) in adipose tissue is not known. Objectives: To determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons an...

  2. Repair of calvarial defects with customised tissue-engineered bone grafts II. Evaluation of cellular efficiency and efficacy in vivo.

    PubMed

    Schantz, Jan-Thorsten; Hutmacher, Dietmar Werner; Lam, Christopher Xu Fu; Brinkmann, Maik; Wong, Kit Mui; Lim, Thiam Chye; Chou, Ning; Guldberg, Robert Erling; Teoh, Swee Hin

    2003-01-01

    We have demonstrated in Part I of this study [see Schantz, J.-T., et al., Tissue Eng. 2003;9(Suppl. 1): S-113-S-126; this issue] that bone marrow-derived progenitor cells and calvarial osteoblasts could be successfully directed into the osteogenic lineage and cultured in three-dimensional (3-D) polycaprolactone (PCL) scaffolds. The objective of the second part of the study was to evaluate and to compare tissue engineered cell-polymer constructs using calvarial osteoblasts (group I) and mesenchymal progenitor cells (MPCs; group II) for the reconstruction of critical-size and three-dimensionally complex cranial defects. In 30 New Zealand White rabbits, bilateral parietal critical-size defects were created. On the basis of computed tomography scans, customized PCL scaffolds with precisely controlled microarchitecture were fabricated, using a rapid prototyping technology. Bone marrow-derived progenitor cells and osteoblasts were isolated and expanded in culture. Osteoblasts (group I) and mesenchymal progenitor cells (group II) were seeded in combination with a fibrin glue suspension into 40 PCL scaffolds. After incubating for 3 days in static culture, the PCL scaffold-cell constructs as well as nonseeded PCL scaffolds (control group) were implanted into 15-mm-diameter calvarial defects. Reconstruction of the cranium and bone formation were evaluated after 3 months. In vivo results indicated osseous tissue integration within the implant and functionally stable restoration of the calvarium. Islands of early bone formation could be observed in X-ray radiographs and in histological sections. Implants showed a high cell:ECM ratio and a dense vascular network. Mechanical testing of the reconstructed area revealed partial integration with the surrounding corticocancellous calvarial bone. The amount (area) of calcification, measured by clinical computed tomography, indicated that cell-seeded constructs measured about 60% more than unrepaired or unseeded scaffolds. Mechanical

  3. The cardiac stem cell compartment is indispensable for myocardial cell homeostasis, repair and regeneration in the adult.

    PubMed

    Nadal-Ginard, Bernardo; Ellison, Georgina M; Torella, Daniele

    2014-11-01

    Resident cardiac stem cells in embryonic, neonatal and adult mammalian heart have been identified by different membrane markers and transcription factors. However, despite a flurry of publications no consensus has been reached on the identity and actual regenerative effects of the adult cardiac stem cells. Intensive research on the adult mammalian heart's capacity for self-renewal of its muscle cell mass has led to a consensus that new cardiomyocytes (CMs) are indeed formed throughout adult mammalian life albeit at a disputed frequency. The physiological significance of this renewal, the origin of the new CMs, and the rate of adult CM turnover are still highly debated. Myocyte replacement, particularly after injury, was originally attributed to differentiation of a stem cell compartment. More recently, it has been reported that CMs are mainly replaced by the division of pre-existing post-mitotic CMs. These latter results, if confirmed, would shift the target of regenerative therapy toward boosting mature CM cell-cycle re-entry. Despite this controversy, it is documented that the adult endogenous c-kit(pos) cardiac stem cells (c-kit(pos) eCSCs) participate in adaptations to myocardial stress, and, when transplanted into the myocardium, regenerate most cardiomyocytes and microvasculature lost in an infarct. Nevertheless, the in situ myogenic potential of adult c-kit(pos) cardiac cells has been questioned. To revisit the regenerative potential of c-kit(pos) eCSCs, we have recently employed experimental protocols of severe diffuse myocardial damage in combination with several genetic murine models and cell transplantation approaches showing that eCSCs are necessary and sufficient for CM regeneration, leading to complete cellular, anatomical, and functional myocardial recovery. Here we will review the available data on adult eCSC biology and their regenerative potential placing it in the context of the different claimed mechanisms of CM replacement. These data are in

  4. A review of the biophysical basis for the clinical application of electric fields in soft-tissue repair.

    PubMed

    Lee, R C; Canaday, D J; Doong, H

    1993-01-01

    Interest in the role of electrical interactions as epigenetic regulators of wound healing had its beginnings nearly 40 years ago. Because the mechanisms of action are not understood (which obviates rational therapy), the empiric application of fields to wounds has produced mixed results. However, taken collectively, clinical trials have demonstrated some beneficial effects. Tests on soft tissues of animals have shown that electric stimulation can influence the rate of wound healing and scar strength. Natural epithelial-derived sodium currents have been discovered in the wounds of invertebrates and mammals. It is theorized that these currents may be a normal controlling factor in wound healing. Therefore, perturbation of these signals is important to understand. The purpose of this review is to put into proper perspective the biophysical, physiological, and clinical data pertaining to use of electricity to control wound healing, with the goal of minimizing much of the prevailing confusion. PMID:8360237

  5. Sirtuins, Tissue Maintenance, and Tumorigenesis

    PubMed Central

    Mohrin, Mary

    2013-01-01

    Aging is a degenerative process resulting in compromised tissue maintenance and increased susceptibility to diseases, such as cancer. Recent advancements support the notion that aging is a highly regulated process governed by evolutionarily conserved pathways. In mammals, tissue-specific adult stem cells (ASCs) persist throughout the lifetime to maintain and repair tissues. While reduced ASC self-renewal is thought to contribute to compromised tissue maintenance, increased self-renewal of cancer stem cells (CSCs) may lead to tumorigenesis. It is speculated that genetic regulators of aging, such as sirtuins, are likely to impinge upon the ASC compartments to regulate tissue maintenance and tumorigenesis. In this review, we discuss the emerging evidence linking sirtuins to normal and malignant ASC self-renewal, tissue maintenance, and tumorigenesis. PMID:24019997

  6. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages.

    PubMed

    Hoeffel, Guillaume; Chen, Jinmiao; Lavin, Yonit; Low, Donovan; Almeida, Francisca F; See, Peter; Beaudin, Anna E; Lum, Josephine; Low, Ivy; Forsberg, E Camilla; Poidinger, Michael; Zolezzi, Francesca; Larbi, Anis; Ng, Lai Guan; Chan, Jerry K Y; Greter, Melanie; Becher, Burkhard; Samokhvalov, Igor M; Merad, Miriam; Ginhoux, Florent

    2015-04-21

    Although classified as hematopoietic cells, tissue-resident macrophages (MFs) arise from embryonic precursors that seed the tissues prior to birth to generate a self-renewing population, which is maintained independently of adult hematopoiesis. Here we reveal the identity of these embryonic precursors using an in utero MF-depletion strategy and fate-mapping of yolk sac (YS) and fetal liver (FL) hematopoiesis. We show that YS MFs are the main precursors of microglia, while most other MFs derive from fetal monocytes (MOs). Both YS MFs and fetal MOs arise from erythro-myeloid progenitors (EMPs) generated in the YS. In the YS, EMPs gave rise to MFs without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal MOs that then seeded embryonic tissues and differentiated into MFs. Thus, adult tissue-resident MFs established from hematopoietic stem cell-independent embryonic precursors arise from two distinct developmental programs. PMID:25902481

  7. A resource of ribosomal RNA-depleted RNA-Seq data from different normal adult and fetal human tissues

    PubMed Central

    Choy, Jocelyn Y.H.; Boon, Priscilla L.S.; Bertin, Nicolas; Fullwood, Melissa J.

    2015-01-01

    Gene expression is the most fundamental level at which the genotype leads to the phenotype of the organism. Enabled by ultra-high-throughput next-generation DNA sequencing, RNA-Seq involves shotgun sequencing of fragmented RNA transcripts by next-generation sequencing followed by in silico assembly, and is rapidly becoming the most popular method for gene expression analysis. Poly[A]+ RNA-Seq analyses of normal human adult tissue samples such as Illumina’s Human BodyMap 2.0 Project and the RNA-Seq atlas have provided a useful global resource and framework for comparisons with diseased tissues such as cancer. However, these analyses have failed to provide information on poly[A]−RNA, which is abundant in our cells. The most recent advances in RNA-Seq analyses use ribosomal RNA-depletion to provide information on both poly[A]+ and poly[A]−RNA. In this paper, we describe the use of Illumina’s HiSeq 2000 to generate high quality rRNA-depleted RNA-Seq datasets from human fetal and adult tissues. The datasets reported here will be useful in understanding the different expression profiles in different tissues. PMID:26594381

  8. Effects of bilingualism and trilingualism in L2 production: evidence from errors and self-repairs in early balanced bilingual and trilingual adults.

    PubMed

    Hsu, Hsiu-ling

    2014-08-01

    Through analyzing response latencies, errors, and self-repairs in Mandarin, this investigation explores how monolingual, bilingual, and trilingual adults process their speech production differently using cognitive control mechanisms. In this study we conducted two experiments involving speech production in Mandarin. In the two experiments, 81 adults participated and were categorized into three groups: Mandarin monolingual, Hakka-Mandarin bilingual, and Hakka-Mandarin-Minnan trilingual. In Experiment 1 (unpreprogrammed task), each subject read 250 targets that were presented on a computer screen, one at a time, using E-prime; in Experiment 2 (preprogrammed task), each subject read 466 targets printed on A4 paper. Experiment 1 showed that bilinguals and trilinguals outperformed monolinguals in every aspect examined in this research, revealing the presence of bilingual and trilingual advantages in inhibitory control. Interestingly, in Experiment 2, we found a more complex pattern of results: a trilingual advantage in attentional control occurred during L2 production in terms of the number of errors and error correction; however, the bilingual group did not maintain this advantage in the task requiring attentional control. These experimental results revealed that the differences between the language groups became clearer when the inhibitory control demands increased and that compared with the trilingual advantage, the bilingual advantage in inhibitory control emerged in more limited contexts. PMID:23754565

  9. TIN DISTRIBUTION IN ADULT RAT TISSUES AFTER EXPOSURE TO TRIMETHYLTIN AND TRIETHYLTIN

    EPA Science Inventory

    The time course of distribution of tin in the adult rat was determined in brain, liver kidney, heart, and blood following single ip administrations of trimethyltin hydroxide (TMT) and triethyltin bromide (TET). Adult Long-Evans rats were killed 1 hr, 4 hr, 12 hr, 24 hr, 5 days, 1...

  10. Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype.

    PubMed

    Tyson, John; Caple, Fiona; Spiers, Alison; Burtle, Brian; Daly, Ann K; Williams, Elizabeth A; Hesketh, John E; Mathers, John C

    2009-05-01

    Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18-30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: ERCC5 Asp1104His (rs17655); XPC Lys939Gln (rs2228001); ERCC2 Lys751Gnl (rs13181); XPC PAT (an 83 bp poly A/T insertion-deletion polymorphism in the XPC gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene-gene interactions were observed between XPC Lys939Gln and ERCC5 Asp1104His and XPC Lys939Gln and ERCC2 Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the ERCC2 Lys751Gnl single nucleotide polymorphism. PMID:18838045

  11. Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging.

    PubMed

    Gifford, Aliya; Towse, Theodore F; Walker, Ronald C; Avison, Malcolm J; Welch, E Brian

    2016-07-01

    Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own. PMID:27166284

  12. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

    PubMed

    Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun

    2016-06-01

    Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials. PMID:27016619

  13. Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury.

    PubMed

    Zhang, Bei; Bailey, William M; Braun, Kaitlyn J; Gensel, John C

    2015-11-01

    Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI. Here we investigate the effect of age on IL-10, a key indicator of M2 macrophage activation. Following mild-moderate SCI in 4 and 14 month old (MO) mice we detected significantly reduced IL-10 expression with age in the injured spinal cord. Specifically, CD86/IL-10 positive macrophages, also known as M2b or regulatory macrophages, were reduced in 14 vs. 4 MO SCI animals. This age-dependent shift in macrophage phenotype was associated with impaired functional recovery and enhanced tissue damage in 14-month-old SCI mice. In vitro, M2b macrophages release anti-inflammatory cytokines without causing neurotoxicity, suggesting that imbalances in the M2b response in 14-month-old mice may be contributing to secondary injury processes. Our data indicate that age is an important factor that regulates SCI inflammation and recovery even to mild-moderate injury. Further, alterations in macrophage activation states may contribute to recovery and we have identified the M2b phenotype as a potential target for therapeutic intervention. PMID:26263843

  14. Topographical guidance of intervertebral disc cell growth in vitro: towards the development of tissue repair strategies for the anulus fibrosus.

    PubMed

    Johnson, William E; Wootton, Andrew; El Haj, Alicia; Eisenstein, Stephen M; Curtis, Adam S; Roberts, Sally

    2006-08-01

    The anulus fibrosus (AF) of the intervertebral disc consists of concentric sheets of collagenous matrix that is synthesised during embryogenesis by aligned disc cells. This highly organised structure may be severely disrupted during disc degeneration and/or herniation. Cell scaffolds that incorporate topographical cues as contact guidance have been used successfully to promote the healing of injured tendons. Therefore, we have investigated the effects of topography on disc cell growth. We show that disc cells from the AF and nucleus pulposus (NP) behaved differently in monolayer culture on micro-grooved membranes of polycaprolactone (PCL). Both cell types aligned to and migrated along the membrane's micro-grooves and ridges, but AF cells were smaller (or less spread), more bipolar and better aligned to the micro-grooves than NP cells. In addition, AF cells were markedly more immunopositive for type I collagen, but less immunopositive for chondroitin-6-sulphated proteoglycans than NP cells. There was no evidence of extracellular matrix (ECM) deposition. Disc cells cultured on non-grooved PCL did not show any preferential alignment at sub-confluence and did not differ in their pattern of immunopositivity to those on grooved PCL. We conclude that substratum topography is effective in aligning disc cell growth and may be useful in tissue engineering for the AF. However, there is a need to optimise cell sources and/or environmental conditions (e.g. mechanical influences) to promote the synthesis of an aligned ECM. PMID:16688474

  15. Adult Mesenchymal Stem Cells and Radiation Injury.

    PubMed

    Kiang, Juliann G

    2016-08-01

    Recent understanding of the cellular and molecular signaling activations in adult mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal for tissue repair and recovery after radiation injury. Thus far, MSCs have been characterized extensively and shown to be useful in mitigation and therapy for acute radiation syndrome and cognitive dysfunction. Use of MSCs for treating radiation injury alone or in combination with additional trauma is foreseeable. PMID:27356065

  16. Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

    PubMed

    Lee, Jeonghwan; Kim, Hye Jin; Cho, Belong; Park, Jin Ho; Choi, Ho Chun; Lee, Cheol Min; Oh, Seung Won; Kwon, Hyuktae; Heo, Nam Ju

    2015-01-01

    Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT) in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61), P for trend 0.016, for the comparisons of lowest vs. highest quartile) and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75), P for trend < 0.001) in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2), male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80), P for trend = 0.009). Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49), P for trend = 0.002). After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25), P for trend = 0.013). Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post-menopausal women

  17. Gelatin-apatite bone mimetic co-precipitates incorporated within biopolymer matrix to improve mechanical and biological properties useful for hard tissue repair.

    PubMed

    Won, Jong-Eun; El-Fiqi, Ahmed; Jegal, Seung-Hwan; Han, Cheol-Min; Lee, Eun-Jung; Knowles, Jonathan C; Kim, Hae-Won

    2014-04-01

    Synthetic biopolymers are commonly used for the repair and regeneration of damaged tissues. Specifically targeting bone, the composite approach of utilizing inorganic components is considered promising in terms of improving mechanical and biological properties. We developed gelatin-apatite co-precipitates which mimic the native bone matrix composition within poly(lactide-co-caprolactone) (PLCL). Ionic reaction of calcium and phosphate with gelatin molecules enabled the co-precipitate formation of gelatin-apatite nanocrystals at varying ratios. The gelatin-apatite precipitates formed were carbonated apatite in nature, and were homogeneously distributed within the gelatin matrix. The incorporation of gelatin-apatite significantly improved the mechanical properties, including tensile strength, elastic modulus and elongation at break, and the improvement was more pronounced as the apatite content increased. Of note, the tensile strength increased to as high as 45 MPa (a four-fold increase vs. PLCL), the elastic modulus was increased up to 1500 MPa (a five-fold increase vs. PLCL), and the elongation rate was ~240% (twice vs. PLCL). These results support the strengthening role of the gelatin-apatite precipitates within PLCL. The gelatin-apatite addition considerably enhanced the water affinity and the acellular mineral-forming ability in vitro in simulated body fluid; moreover, it stimulated cell proliferation and osteogenic differentiation. Taken together, the GAp-PLCL nanocomposite composition is considered to have excellent mechanical and biological properties, which hold great potential for use as bone regenerative matrices. PMID:23985536

  18. Meniscal repair following meniscectomy: mechanism and protective effect. Experimental study in the dog.

    PubMed

    Berjon, J J; Munuera, L; Calvo, M

    1990-01-01

    Meniscal repair was studied to evaluate the mechanism and its potential protective effects on the articular cartilage in an experimental model consisting of 68 knees of adult dogs on which five different types of medial meniscectomy were performed. The results were assessed by macroscopic, microangiographic, and histological methods, after a sequential follow-up period of 10-450 days. Two different mechanisms of meniscal repair were observed, depending on whether meniscal section had been performed in vascular (total meniscectomy) or avascular (subtotal or partial meniscectomy) zones. It was also observed that the repaired meniscal tissue does not prevent articular cartilage degeneration. This is more closely related to the size of the meniscal fragment preserved at meniscectomy. Due to the biomechanical importance of the meniscus and the lack of functional relevance of the repaired meniscal tissue, the most conservative approach possible to meniscectomy is recommended. PMID:1703666

  19. 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

  20. Evaluation of soft-tissue morphology of the face in 1,050 young adults.

    PubMed

    Borman, H; Ozgür, F; Gürsu, G

    1999-03-01

    Anthropometry of the face has always been an interesting subject for artists and plastic surgeons. Since ancient times, many rules have been proposed for the ideal face. The authors measured directly vertical and horizontal proportions of the face and inclinations of the soft-tissue facial profile in 1050 young Turkish adults. Differences between the facial measurements of subjects from seven different geographic regions were analyzed. Some of the measurements were compared further with the measurements of other populations in the literature, and the validity of the neoclassical canons were tested. The special head height measure was shorter than the special face height in the majority of our study group (women/men: equal height, 13%/15%; longer special head height, 28%/30%; shorter special head height, 59%/55%). Faces with three equally high-profile sections were not seen in women or in men. When the forehead height was compared with the nose height, equality was present in a small percentage of the population (women/men: equal height, 17%/18%; longer forehead, 41%/ 42%; shorter forehead, 42%/40%). The nose height was equal to the lower face height in a minority of the population (women/men: equal height, 10%/11%; longer nose, 9%/11%; shorter nose (81%/78%). The forehead height was shorter than the lower face height in the majority of the population (women/ men: equal height, 8%/9%; longer forehead, 12%/13%; shorter forehead, 79%/78%). The intercanthal distance was shorter than the nose width in the majority of the population (women/men: equal width, 20%/19%; wider intercanthal distance, 35%/37%; narrower intercanthal width, 65%/68%). The population was distributed evenly in regard to the variations of the orbital proportion canon (women/men: equal intercanthal width and eye fissure length, 31%/36%; wider intercanthal distance, 34%/27%; narrower intercanthal width, 35%/37%). The mouth width was greater than 1.5 times the nose width in the majority of the

  1. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C.

    PubMed

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-05-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the (14)C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of (14)C, produced by nuclear bomb tests in 1955-1963, which is reflected in all living organisms. Levels of (14)C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945-1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of (14)C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of (14)C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, (14)C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue. PMID:23401563

  2. Single Stage Repair for Aortic Coarctation associated with Intracardiac Defects Using Extra-Anatomic Bypass Graft in Adults

    PubMed Central

    Ates, Mehmet Sanser; Onuk, Burak Emre; Bakkaloglu, Beyhan; Sungur, Umit Pinar; Kurtoglu, Murat; Karagoz, Yahya Halidun

    2016-01-01

    Background and Objectives Coarctation of the aorta in adulthood is generally associated with other cardiovascular disorders requiring surgical management. An extra anatomic bypass grafting from the ascending to descending aorta by posterior pericardial approach via median sternotomy could be a reasonable single stage surgical strategy for these patients. Subjects and Methods Seven male patients aged between 14-41 years underwent an extra anatomic bypass grafting for coarctation repair concomitantly with the surgical management of the associated cardiovascular disorders via median sternotomy. Preoperative mean systolic arterial blood pressure was 161.8±24.5 mmHg, although the patients were under treatment of different combinations of antihypertensive agents. Additional surgical procedures were: aortic valve replacement (n=4), ventricular septal defect (VSD) closure (n=2), ascending aortic replacement (n=3) and Bentall procedure (n=1). None of our patients have been previously diagnosed or operated on for coarctation. Data were evaluated during their hospital stay and in post-operative follow-up. Results The post-operative course was uneventful in all but one patient was re-operated on due to bleeding. There was neither mortality nor significant morbidity during the in-hospital period and all patients were discharged within 5-9 (mean: 6.3±1.5) days. The mean follow up period was 71.83±23 months (range: 23-95 months). Unfortunately one of our patients could not be contacted for a follow up period because of invalid personal data. Conclusion Coarctation of the aorta in adulthood associated with other cardiovascular disorders can be operated on simultaneously via an extra anatomic bypass grafting technique with low morbidity and mortality. PMID:27482266

  3. Clubfoot repair

    MedlinePlus

    ... release; Talipes equinovarus - repair; Tibialis anterior tendon transfer Images Clubfoot repair - series References Kelly DM. Congenital Anomalies ... provided herein should not be used during any medical emergency or for the diagnosis or treatment of ...

  4. Assessing the repair of critical size bone defects performed in a goat tibia model using tissue-engineered constructs cultured in a bidirectional flow perfusion bioreactor.

    PubMed

    Gardel, Ls; Afonso, M; Frias, C; Gomes, Me; Reis, Rl

    2014-01-01

    This work evaluated in vivo performance of a tissue-engineered bone-like matrix obtained by culturing cell-scaffold constructs in a flow perfusion bioreactor, designed to enable culture of large constructs, envisioning the regeneration of critical-sized defects. A blend of starch with polycaprolactone scaffolds was seeded with goat bone marrow stromal cells (GBMSCs) cultured in the perfusion bioreactor for 14 days using osteogenic medium. Cell seeded scaffolds cultured in static conditions acted as controls. After 14 days, constructs (42 mm length and 16 mm in diameter) were implanted in critical size defects performed in the tibial bone of six adult goats from which the bone marrow had been collected previously. Explants were retrieved after six and 12 weeks of implantation and characterized using scanning electron microscopy, energy-dispersive spectroscopy, micro-computed tomography and radiographic analysis to assess tissue morphology and calcification. Explants were histologically analyzed, using Hematoxylin & Eosin and Masson Trichrome staining. Results provided relevant information about the performance and functionality of starch with polycaprolactone-goat bone marrow stromal cell constructs in a critical size orthotopic defect performed in a large animal model and demonstrated that culture of the starch with polycaprolactone scaffolds with the autologous cells in perfusion culture provide a good therapy for the healing and regenerative process of bone defects. PMID:24413026

  5. Avian Soft Tissue Surgery.

    PubMed

    Guzman, David Sanchez-Migallon

    2016-01-01

    Basic surgical instrumentation for avian soft tissue surgery includes soft tissue retractors, microsurgical instrumentation, surgical loupes, and head-mounted lights. Hemostasis is fundamental during the surgical procedures. The indications, approach, and complications associated with soft tissue surgeries of the integumentary (digit constriction repair, feather cyst excision, cranial wound repair, sternal wound repair, uropygial gland excision), gastrointestinal (ingluviotomy, crop biopsy, crop burn repair, celiotomy, coelomic hernia and pseudohernia repair, proventriculotomy, ventriculotomy, enterotomy, intestinal resection and anastomosis, cloacoplasty, cloacopexy), respiratory (rhinolith removal, sinusotomy, tracheotomy, tracheal resection and anastomosis, tracheostomy, pneumonectomy) and reproductive (ovocentesis, ovariectomy, salpingohysterectomy, cesarean section, orchidectomy, vasectomy, phallectomy) systems are reviewed. PMID:26611927

  6. Emergent properties of neural repair: elemental biology to therapeutic concepts.

    PubMed

    Carmichael, S Thomas

    2016-06-01

    Stroke is the leading cause of adult disability. The past decade has seen advances in basic science research of neural repair in stroke. The brain forms new connections after stroke, which have a causal role in recovery of function. Brain progenitors, including neuronal and glial progenitors, respond to stroke and initiate a partial formation of new neurons and glial cells. The molecular systems that underlie axonal sprouting, neurogenesis, and gliogenesis after stroke have recently been identified. Importantly, tractable drug targets exist within these molecular systems that might stimulate tissue repair. These basic science advances have taken the field to its first scientific milestone; the elemental principles of neural repair in stroke have been identified. The next stages in this field involve understanding how these elemental principles of recovery interact in the dynamic cellular systems of the repairing brain. Emergent principles arise out of the interaction of the fundamental or elemental principles in a system. In neural repair, the elemental principles of brain reorganization after stroke interact to generate higher order and distinct concepts of regenerative brain niches in cellular repair, neuronal networks in synaptic plasticity, and the distinction of molecular systems of neuroregeneration. Many of these emergent principles directly guide the development of new therapies, such as the necessity for spatial and temporal control in neural repair therapy delivery and the overlap of cancer and neural repair mechanisms. This review discusses the emergent principles of neural repair in stroke as they relate to scientific and therapeutic concepts in this field. Ann Neurol 2016;79:895-906. PMID:27043816

  7. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

    PubMed Central

    Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  8. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis.

    PubMed

    Zhang, Hongyu; Siegel, Christopher T; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2(+) cells) that were isolated from healthy adult mouse liver by using a "Percoll-Plate-Wait" procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 10(6) cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2(+) cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2(+) cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  9. In vivo adeno-associated viral vector-mediated genetic engineering of white and brown adipose tissue in adult mice.

    PubMed

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-12-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes. PMID:24043756

  10. In Vivo Adeno-Associated Viral Vector–Mediated Genetic Engineering of White and Brown Adipose Tissue in Adult Mice

    PubMed Central

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-01-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes. PMID:24043756

  11. Stem cells and exosomes in cardiac repair.

    PubMed

    Singla, Dinender K

    2016-04-01

    Cardiac diseases currently lead in the number of deaths per year, giving rise an interest in transplanting embryonic and adult stem cells as a means to improve damaged tissue from conditions such as myocardial infarction and coronary artery disease. After testing these cells as a treatment option in both animal and human models, it is believed that these cells improve the damaged tissue primarily through the release of autocrine and paracrine factors. Major concerns such as teratoma formation, immune response, difficulty harvesting cells, and limited cell proliferation and differentiation, hinder the routine use of these cells as a treatment option in the clinic. The advent of stem cell-derived exosomes circumvent those concerns, while still providing the growth factors, miRNA, and additional cell protective factors that aid in repairing and regenerating the damaged tissue. These exosomes have been found to be anti-apoptotic, anti-fibrotic, pro-angiogenic, as well as enhance cardiac differentiation, all of which are key to repairing damaged tissue. As such, stem cell derived exosomes are considered to be a potential new and novel approach in the treatment of various cardiac diseases. PMID:26848944

  12. Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

    PubMed Central

    Barrientos-Durán, Antonio; Carpenter, Ellen M; zur Nieden, Nicole I; Malinin, Theodore I; Rodríguez-Manzaneque, Juan Carlos; Zanello, Laura P

    2014-01-01

    The clinical management of bone defects caused by trauma or nonunion fractures remains a challenge in orthopedic practice due to the poor integration and biocompatibility properties of the scaffold or implant material. In the current work, the osteogenic properties of carboxyl-modified single-walled carbon nanotubes (COOH–SWCNTs) were investigated in vivo and in vitro. When human preosteoblasts and murine embryonic stem cells were cultured on coverslips sprayed with COOH–SWCNTs, accelerated osteogenic differentiation was manifested by increased expression of classical bone marker genes and an increase in the secretion of osteocalcin, in addition to prior mineralization of the extracellular matrix. These results predicated COOH–SWCNTs’ use to further promote osteogenic differentiation in vivo. In contrast, both cell lines had difficulties adhering to multi-walled carbon nanotube-based scaffolds, as shown by scanning electron microscopy. While a suspension of SWCNTs caused cytotoxicity in both cell lines at levels >20 μg/mL, these levels were never achieved by release from sprayed SWCNTs, warranting the approach taken. In vivo, human allografts formed by the combination of demineralized bone matrix or cartilage particles with SWCNTs were implanted into nude rats, and ectopic bone formation was analyzed. Histological analysis of both types of implants showed high permeability and pore connectivity of the carbon nanotube-soaked implants. Numerous vascularization channels appeared in the formed tissue, additional progenitor cells were recruited, and areas of de novo ossification were found 4 weeks post-implantation. Induction of the expression of bone-related genes and the presence of secreted osteopontin protein were also confirmed by quantitative polymerase chain reaction analysis and immunofluorescence, respectively. In summary, these results are in line with prior contributions that highlight the suitability of SWCNTs as scaffolds with high bone

  13. Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint.

    PubMed

    Lemos, George Azevedo; Rissi, Renato; de Souza Pires, Ivan Luiz; de Oliveira, Letícia Prado; de Aro, Andrea Aparecida; Pimentel, Edson Rosa; Palomari, Evanisi Teresa

    2016-08-01

    The objective of this study was to characterize morphological and biochemistry action of low-level laser therapy (LLLT) on induced arthritis in the temporomandibular joint (TMJ) of rats. Twenty-four male Wistar rats were randomly divided into groups with 12 animals each: (AG) group with arthritis induced in the left TMJ and (LG) group with arthritis induced in the left TMJ and treated with LLLT (830 nm, 30 mW, 3 J/cm(2)). Right TMJs in the AG group were used as noninjected control group (CG). Arthritis was induced by intra-articular injection of 50 μl Complete Freund's Adjuvant (CFA) and LLLT began 1 week after arthritis induction. Histopathological analysis was performed using sections stained with hematoxylin-eosin, Toluidine Blue, and picrosirius. Biochemical analysis was determined by the total concentration of sulfated glycosaminoglycans (GAGs) and evaluation of matrix metalloproteinases (MMP-2 and MMP-9). Statistical analysis was performed using paired and unpaired t tests, with p < 0.05. Compared to AG, LG had minor histopathological changes in the TMJ, smaller thickness of the articular disc in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001), high birefringence of collagen fibers in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001) on the articular disc, and statistically lower activity of MMP-2 latent (p < 0.0001), MMP-2 active (P = 0.02), MMP-9 latent (p < 0.0001), and MMP-9 active (p < 0.0001). These results suggest that LLLT can increase the remodeling and enhancing tissue repair in TMJ with induced arthritis. PMID:27147076

  14. Spread patterns and effectiveness for surgery after ultrasound-guided rectus sheath block in adult day-case patients scheduled for umbilical hernia repair

    PubMed Central

    Manassero, Alberto; Bossolasco, Matteo; Meineri, Maurizio; Ugues, Susanna; Liarou, Chrysoula; Bertolaccini, Luca

    2015-01-01

    Background and Aims: We conducted a prospective study to examine the local anesthetic (LA) spread and the effectiveness for surgical anesthesia of ultrasound (US)-guided rectus sheath block (RSB) in adult patients undergoing umbilical hernia repair. Material and Methods: Thirty patients received at T-10 level a bilateral US-guided injection of 20 mL levobupivacaine 0.375% + epinephrine 5 μg/mL behind the rectus muscle to detach it from its sheath. Anesthetic spread into the rectus sheath was evaluated ultrasonographically at T-9 and T-11 levels and scored from 0 to 4. The RSB was defined effective for surgical anesthesia if it was able to guarantee an anesthetic level sufficient for surgery without any mepivacaine supplementation. Results: Overall, the block was effective for surgical anesthesia in 53.3% of patients (95% confidence interval, ±17.8). In the remaining patients, anesthesia supplementation was needed at cutaneous incision, whereas manipulation of the muscle and fascial planes was painless. No patients required general anesthesia. LA spreads as advocated (to T-9 and to T-11 bilaterally = spread score 4) in 8/30 patients (26.6%); in these cases, the block was 75% effective for surgery. The anesthetic spread was most negatively influenced by increased body mass index. Postoperative analgesia was excellent in 97% of patients. Conclusion: Use of RSB as an anesthetic management of umbilical herniorrhaphy is recommended only with anesthetic supplementation at the incision site. PMID:26330714

  15. The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease.

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-08-01

    Expression of microRNA (miR)-126 is enriched in endothelial cells (ECs) and endothelial progenitor cells (EPCs). MiR-126 is considered a master regulator of physiological angiogenesis. In embryonic vasculogenesis, this miRNA is involved in induction of angiogenic signaling, supports differentiation of embryonic stem cells to EPCs and ECs, and promotes EC maturation. However, in mature ECs and adult EPCs, miR-126 contributes to vascular homeostasis by inhibiting angiogenesis and maintaining the quiescent endothelial phenotype associated with increased vascular integrity and inhibited proliferation and motility. In a case of vessel injury and/or hypoxia, miR-126 up-regulation activates EPCs and ECs and contributes to vascular healing and neovessel formation. Indeed, miR-126 exhibits vasculoprotective and atheroprotective properties. The promising regenerative and proangiogenic potential of this miRNA will be helpful for development of cardioprotective strategies and cardiovascular repair therapies of myocardial infarction, heart failure, and other cardiovascular pathology. PMID:27180261