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Sample records for regenerative medicine present

  1. Regenerative medicine and organ transplantation: past, present, and future.

    PubMed

    Orlando, Giuseppe; Wood, Kathryn J; Stratta, Robert J; Yoo, James J; Atala, Anthony; Soker, Shay

    2011-06-27

    This overview traces the history of regenerative medicine pertinent to organ transplantation, illustrates potential clinical applications reported to date, and highlights progress achieved in the field of complex modular organ engineering. Regenerative medicine can now produce relatively simple tissues such as skin, bladders, vessels, urethras, and upper airways, whereas engineering or generation of complex modular organs remains a major challenge. Ex vivo organ engineering may benefit from complementary investigations in the fields of developmental biology and stem cells and transplantation before its full potential can be realized.

  2. Tissue engineering and regenerative medicine: past, present, and future.

    PubMed

    Salgado, António J; Oliveira, Joaquim M; Martins, Albino; Teixeira, Fábio G; Silva, Nuno A; Neves, Nuno M; Sousa, Nuno; Reis, Rui L

    2013-01-01

    Tissue and organ repair still represents a clinical challenge. Tissue engineering and regenerative medicine (TERM) is an emerging field focused on the development of alternative therapies for tissue/organ repair. This highly multidisciplinary field, in which bioengineering and medicine merge, is based on integrative approaches using scaffolds, cell populations from different sources, growth factors, nanomedicine, gene therapy, and other techniques to overcome the limitations that currently exist in the clinics. Indeed, its overall objective is to induce the formation of new functional tissues, rather than just implanting spare parts. This chapter aims at introducing the reader to the concepts and techniques of TERM. It begins by explaining how TERM have evolved and merged into TERM, followed by a short overview of some of its key aspects such as the combinations of scaffolds with cells and nanomedicine, scaffold processing, and new paradigms of the use of stem cells for tissue repair/regeneration, which ultimately could represent the future of new therapeutic approaches specifically aimed at clinical applications.

  3. Will Regenerative Medicine Replace Transplantation?

    PubMed Central

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J.; Atala, Anthony

    2013-01-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs. PMID:23906883

  4. Regenerative medicine blueprint.

    PubMed

    Terzic, Andre; Harper, C Michel; Gores, Gregory J; Pfenning, Michael A

    2013-12-01

    Regenerative medicine, a paragon of future healthcare, holds unprecedented potential in extending the reach of treatment modalities for individuals across diseases and lifespan. Emerging regenerative technologies, focused on structural repair and functional restoration, signal a radical transformation in medical and surgical practice. Regenerative medicine is poised to provide innovative solutions in addressing major unmet needs for patients, ranging from congenital disease and trauma to degenerative conditions. Realization of the regenerative model of care predicates a stringent interdisciplinary paradigm that will drive validated science into standardized clinical options. Designed as a catalyst in advancing rigorous new knowledge on disease causes and cures into informed delivery of quality care, the Mayo Clinic regenerative medicine blueprint offers a patient-centered, team-based strategy that optimizes the discovery-translation-application roadmap for the express purpose of science-supported practice advancement.

  5. Cytomics in regenerative medicine

    NASA Astrophysics Data System (ADS)

    Tárnok, Attila; Pierzchalski, Arkadiusz

    2008-02-01

    Cytomics is the high-content analysis of cell-systems [6, 78]. The area of Cytomics and Systems Biology received great attention during the last years as it harbours the promise to substantially impact on various fields of biomedicine, drug discovery, predictive medicine [6] and may have major potential for regenerative medicine. In regenerative medicine Cytomics includes process control of cell preparation and culturing using non-invasive detection techniques, quality control and standardization for GMP and GLP conformity and even prediction of cell fate based on sophisticated data analysis. Cytomics requires quantitative and stoichiometric single cell analysis. In some areas the leading cytometric techniques represent the cutting edge today. Many different applications/variations of multicolour staining were developed for flow- or slide-based cytometry (SBC) analysis of suspensions and sections to whole animal analysis [78]. SBC has become an important analytical technology in drug discovery, diagnosis and research and is an emerging technology for systems analysis [78]. It enables high-content high-throughput measurement of cell suspensions, cell cultures and tissues. In the last years various commercial SBC instruments were launched principally enabling to perform similar tasks. Standardisation as well as comparability of different instruments is a major challenge. Hyperspectral optical imaging may be implemented in SBC analysis for label free cell detection based on cellular autofluorescence [3]. All of these developments push the systemic approach of the analysis of biological specimens to enhance the outcome of regenerative medicine.

  6. Evaluating the Past, Present, and Future of Regenerative Medicine: A Global View.

    PubMed

    Ronfard, Vincent; Vertès, Alain A; May, Michael H; Dupraz, Anne; van Dyke, Mark E; Bayon, Yves

    2017-04-01

    "Evaluating the Past and Present of Regenerative Medicine (RM)" was the first part of an Industry Symposium dedicated to the subject during the 2015 TERMIS World Congress in Boston. This working session presented a critical review of the current RM landscape in Europe and North America with possible projections for the future. Interestingly, the RM development cycle seems to obey the Gartner hype cycle, now at the enlightenment phase, after past exaggerated expectations and discouragements, as suggested by increasing numbers of clinical trials and recent market approvals of RM solutions in both Europe (Glybera and Holoclar(®) from Chiesi Pharma and Strimvelis(®) from GSK) and Japan (Remestemcel-L from Mesoblast(®)). The successful commercial translation of RM research is governed by five major drivers: (i) fully validated manufacturing capability for autologous or allogeneic products, (ii) reimbursement for targeted clinical indications with high and demonstrable medico-economic benefits versus standard of care, (iii) implication of regulatory bodies in the design and development plan of any RM solution, which should be well characterized, robust, with proven consistent efficacy and an acceptable and controlled positive benefit/risk ratio, (iv) collaborations facilitated by multicompetence hubs/consortia of excellence, (v) well-thought-out clinical development plans for reducing the risk of failure. Benefiting from past and present experience, the RM burgeoning industry is expected to accelerate the market release of cost-effective RM products with real curative potential for specific clinical indications with high unmet needs. This should be achieved by wisely leveraging all possible synergies of the different stakeholders, for example, patients, clinicians, reimbursement and health technology assessment (HTA) agencies, regulatory authorities, public/private investors, academia, and companies.

  7. Personalized Regenerative Medicine.

    PubMed

    Arjmand, Babak; Goodarzi, Parisa; Mohamadi-Jahani, Fereshteh; Falahzadeh, Khadijeh; Larijani, Bagher

    2017-03-01

    Personalized medicine as a novel field of medicine refers to the prescription of specific therapeutics procedure for an individual. This approach has established based on pharmacogenetic and pharmacogenomic information and data. The terms precision and personalized medicines are sometimes applied interchangeably. However, there has been a shift from "personalized medicine" towards "precision medicine". Although personalized medicine emerged from pharmacogenetics, nowadays it covers many fields of healthcare. Accordingly, regenerative medicine and cellular therapy as the new fields of medicine use cell-based products in order to develop personalized treatments. Different sources of stem cells including mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs) have been considered in targeted therapies which could give many advantages. iPSCs as the novel and individual pluripotent stem cells have been introduced as the appropriate candidates for personalized cell therapies. Cellular therapies can provide a personalized approach. Because of person-to-person and population differences in the result of stem cell therapy, individualized cellular therapy must be adjusted according to the patient specific profile, in order to achieve best therapeutic results and outcomes. Several factors should be considered to achieve personalized stem cells therapy such as, recipient factors, donor factors, and the overall body environment in which the stem cells could be active and functional. In addition to these factors, the source of stem cells must be carefully chosen based on functional and physical criteria that lead to optimal outcomes.

  8. Hydrogels in Regenerative Medicine

    PubMed Central

    Slaughter, Brandon V.; Khurshid, Shahana S.; Fisher, Omar Z.; Khademhosseini, Ali

    2015-01-01

    Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field. PMID:20882499

  9. Stem cell research and regenerative medicine in 2014: first year of regenerative medicine in Japan.

    PubMed

    Okano, Hideyuki

    2014-09-15

    It is my great pleasure to announce that we were able to publish the Japan Issue in Stem Cells and Development, especially in this year 2014. This year, 2014, is said to be the First Year of Regenerative Medicine in Japan. This movement is likely to be based on the establishment of a new law system regarding regenerative medicine (an Act for Ensuring the Safety of Regenerative Medicine or the so-called Regenerative Medicine Law) and the partial revision of the Pharmaceutical Affairs Law (PAL). Both laws will come into effect in 2014 in this country. These new law systems are expected to have a great impact on the facilitation of R&D related to regenerative medicine and stem cell biology. In the present Japan Issue, some excellent stem cell research in this country will be introduced to celebrate the First Year of Regenerative Medicine in Japan.

  10. Regenerative Medicine Build-Out

    PubMed Central

    Pfenning, Michael A.; Gores, Gregory J.; Harper, C. Michel

    2015-01-01

    Summary Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Significance Regenerative medicine is at the

  11. Regenerative Medicine Build-Out.

    PubMed

    Terzic, Andre; Pfenning, Michael A; Gores, Gregory J; Harper, C Michel

    2015-12-01

    Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Regenerative medicine is at the vanguard of health care

  12. The pharmacology of regenerative medicine.

    PubMed

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

    2013-07-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  13. Applications of regenerative medicine in organ transplantation.

    PubMed

    Jain, Aditya; Bansal, Ramta

    2015-01-01

    A worldwide shortage of organs for clinical implantation establishes the need to bring forward and test new technologies that will help in solving the problem. The concepts of regenerative medicine hold the potential for augmenting organ function or repairing damaged organ or allowing regeneration of deteriorated organs and tissue. Researchers are exploring possible regenerative medicine applications in organ transplantation so that coming together of the two fields can benefit each other. The present review discusses the strategies that are being implemented to regenerate or bio-engineer human organs for clinical purposes. It also highlights the limitations of the regenerative medicine that needs to be addressed to explore full potential of the field. A web-based research on MEDLINE was done using keywords "regenerative medicine," "tissue-engineering," "bio-engineered organs," "decellularized scaffold" and "three-dimensional printing." This review screened about 170 articles to get the desired knowledge update.

  14. The Pharmacology of Regenerative Medicine

    PubMed Central

    Saul, Justin M.; Furth, Mark E.; Andersson, Karl-Erik

    2013-01-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase “regenerative pharmacology” to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is “the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues.” As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all. PMID:23818131

  15. Decellularized scaffolds in regenerative medicine

    PubMed Central

    Yu, Yaling; Alkhawaji, Ali; Ding, Yuqiang; Mei, Jin

    2016-01-01

    Allogeneic organ transplantation remains the ultimate solution for end-stage organ failure. Yet, the clinical application is limited by the shortage of donor organs and the need for lifelong immunosuppression, highlighting the importance of developing effective therapeutic strategies. In the field of regenerative medicine, various regenerative technologies have lately been developed using various biomaterials to address these limitations. Decellularized scaffolds, derived mainly from various non-autologous organs, have been proved a regenerative capability in vivo and in vitro and become an emerging treatment approach. However, this regenerative capability varies between scaffolds as a result of the diversity of anatomical structure and cellular composition of organs used for decellularization. Herein, recent advances in scaffolds based on organ regeneration in vivo and in vitro are highlighted along with aspects where further investigations and analyses are needed. PMID:27486772

  16. Regenerative Medicine Applications in Wound Care.

    PubMed

    Ali Nilforoushzadeh, Mohammad; Mollapour Sisakht, Mahsa; Marcus Seifalian, Alexander; Amir Amirkhani, Mohammad; Reza Banafsheh, Hamid; Verdi, Javad; Sharifzad, Farzaneh; Taghiabadi, Ehsan

    2017-09-29

    During the last two decades, a number of studies have been published on different aspects of regenerative medicine in the field of dermatology. The following article aims at integrating all available information about regenerative dermatology, from the past to the present. In addition, we focused on most well-known application of regenerative medicine in dermatology field, wound healing, especially for burns and non-healing wounds based on available skin replacement in market. The present review focuses on providing an overview on available products in market and on-going clinical trials. These are valuable to get the picture of latest trends and also helpful for clinicians. In future, regenerative dermatology may encompass more effective and time-saving therapies for treating skin injuries and diseases. However, more clinical trials are required to establish standardized protocols and ascertain the safety, long-term effects, and efficacy of the novel therapeutic methods in regenerative dermatology. Despite several improvements in this field, extensive research is required for performing successful and precise clinical trials in future. Further improvements would enable the researchers to develop new products in this field. In this review, we have discussed the most recent breakthroughs in the field of regenerative dermatology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Electrospun Nanofibers for Regenerative Medicine**

    PubMed Central

    Liu, Wenying; Thomopoulos, Stavros

    2013-01-01

    This article reviews recent progress in applying electrospun nanofibers to the emerging field of regenerative medicine. We begin with a brief introduction to electrospinning and nanofibers, with a focus on issues related to the selection of materials, incorporation of bioactive molecules, degradation characteristics, control of mechanical properties, and facilitation of cell infiltration. We then discuss a number of approaches to fabrication of scaffolds from electrospun nanofibers, including techniques for controlling the alignment of nanofibers and for producing scaffolds with complex architectures. We also highlight applications of the nanofiber-based scaffolds in four areas of regenerative medicine that involve nerves, dural tissues, tendons, and the tendon-to-bone insertion site. We conclude this review with perspectives on challenges and future directions for design, fabrication, and utilization of scaffolds based on electrospun nanofibers. PMID:23184683

  18. Regenerative medicine in kidney disease.

    PubMed

    Little, Melissa H; Kairath, Pamela

    2016-08-01

    The treatment of renal failure has changed little in decades. Organ transplantation and dialysis continue to represent the only therapeutic options available. However, decades of fundamental research into the response of the kidney to acute injury and the processes driving progression to chronic kidney disease are beginning to open doors to new options. Similarly, continued investigations into the cellular and molecular basis of normal kidney development, together with major advances in stem cell biology, are now delivering options in regenerative medicine not possible as recently as a decade ago. In this review, we will discuss advances in regenerative medicine as it may be applied to the kidney. This will cover cellular therapies focused on ameliorating injury and improving repair as well as advancements in the generation of new renal tissue from stem/progenitor cells. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  19. Where is dentistry in regenerative medicine?

    PubMed

    Ricci, John L; Terracio, Louis

    2011-08-01

    Where does dentistry fit into the field of regenerative medicine? Based on the fact that the goal of regenerative medicine is to restore function to damaged organs and tissues, it is apparent that dentistry, which has long embraced the concept of restoring function of damaged teeth, has embraced this goal from the very beginning. In this brief review we present the opinion that if you take as the primary criterion the restoration of tissue and organ function, dentistry has not only been at the forefront of restorative medicine but actually predates it in practice. We illustrate the depth and breadth of dental regenerative medicine using examples of therapies or potential therapies from our laboratories. These begin with an example from a historical area of strength, dental implant design and fabrication, progress to a more high tech bone scaffold fabrication project, and finish with a stem cell-based soft tissue engineering project. In the final analysis we believe that the restorative nature of dentistry will keep it at the forefront of regenerative medicine. © 2011 FDI World Dental Federation.

  20. CMD kinetics and regenerative medicine

    PubMed Central

    Anjamrooz, Seyed Hadi

    2016-01-01

    The author’s theory of the cell memory disc (CMD) offers a radical and holistic picture of the cell from both functional and structural perspectives. Despite all of the attention that has been focused on different regenerative strategies, several serious CMD-based obstacles still remain that make current cell therapies inherently unethical, harmful, and largely ineffective from a clinical viewpoint. Accordingly, unless there is a real breakthrough in finding an alternative or complementary approach to overcome these barriers, all of the discussion regarding cell-based therapies may be fruitless. Hence, this paper focuses on the issue of CMD kinetics in an attempt to provide a fresh perspective on regenerative medicine. PMID:27186287

  1. Applications of regenerative medicine in organ transplantation

    PubMed Central

    Jain, Aditya; Bansal, Ramta

    2015-01-01

    A worldwide shortage of organs for clinical implantation establishes the need to bring forward and test new technologies that will help in solving the problem. The concepts of regenerative medicine hold the potential for augmenting organ function or repairing damaged organ or allowing regeneration of deteriorated organs and tissue. Researchers are exploring possible regenerative medicine applications in organ transplantation so that coming together of the two fields can benefit each other. The present review discusses the strategies that are being implemented to regenerate or bio-engineer human organs for clinical purposes. It also highlights the limitations of the regenerative medicine that needs to be addressed to explore full potential of the field. A web-based research on MEDLINE was done using keywords “regenerative medicine,” “tissue-engineering,” “bio-engineered organs,” “decellularized scaffold” and “three-dimensional printing.” This review screened about 170 articles to get the desired knowledge update. PMID:26229352

  2. Regenerative Medicine in Alzheimer's Disease

    PubMed Central

    Felsenstein, Kevin M.; Candelario, Kate M.; Steindler, Dennis A.; Borchelt, David R.

    2013-01-01

    Identifying novel, effective therapeutics for Alzheimer's disease (AD) is one of the major unmet medical needs for the coming decade. Because the current paradigm for developing and testing disease modifying AD therapies is protracted and likely to be even longer with the shift towards earlier intervention in pre-clinical AD, it is an open question whether we can develop, test, and widely deploy a novel therapy in time to help the current at-risk generation if we continue to follow the standard paradigms of discovery and drug development. There is an imperative need to find safe and effective preventative measures that can be rapidly deployed to stem the coming wave of AD that will potentially engulf the next generation. We can broadly define regenerative medicine as approaches that use stem-cell-based therapies or approaches that seek to modulate inherent neurogenesis. Neurogenesis, though most active during pre-natal development has been shown to continue in several small parts of the brain, which includes the hippocampus and the subventricular zone, suggesting its potential to reverse cognitive deficits. If AD pathology impacts neurogenesis then it follows that conditions that stimulate endogenous neurogenesis (e.g., environmental stimuli, physical activity, trophic factors, cytokines, and drugs) may help to promote the regenerative and recovery process. Herein, we review the complex logistics of potentially implementing neurogenesis-based therapeutic strategies for the treatment of AD. PMID:24286919

  3. [Regenerative medicine: history and perspectives].

    PubMed

    Okabayashi, Koji; Asashima, Makoto

    2008-05-01

    Regenerative medicine using stem cells is one of the most important topics today. Embryonic stem cells (ES cells) are useful in the studies of the differentiation of various cells or tissues for transplantation therapy, because of their pluripotency to differentiate into almost all types of cells in the body. However, it is controversial to use human ES cells, because it is necessary to sacrifice the life of human embryos for the establishment of these cells. Induced pluripotent stem cells (iPS cells) generated from somatic cells of patients are one of the alternative sources of human pluripotent stem cells while avoiding ethical problems. Epigenetic studies using iPS cells may be valuable to find the way to control cell differentiation more effectively.

  4. Regenerative medicine for neurological disorders.

    PubMed

    Park, Dong-Hyuk; Eve, David J; Chung, Yong-Gu; Sanberg, Paul R

    2010-03-16

    The annual meeting of the American Society for Neural Therapy and Repair (ASNTR) has always introduced us to top-notch and up-to-date approaches for regenerative medicine related to neuroscience, ranging from stem cell-based therapy to novel drugs. The 16th ASNTR meeting focused on a variety of different topics, including the unknown pathogenesis or mechanisms of specific neurodegenerative diseases, stem cell biology, and development of novel alternative medicines or devices. Newly developed stem cells, such as amniotic epithelial stem cells and induced pluripotent stem cells, as well as well-known traditional stem cells, such as neural, embryonic, bone marrow mesenchymal, and human umbilical cord blood-derived stem cells, were reported. A number of commercialized stem cells were also covered at this meeting. Fetal neural tissues, such as ventral mesencephalon, striatum, and Schwann cells, were investigated for neurodegenerative diseases or spinal cord injury. A number of studies focused on novel methods for drug monitoring or graft tracking, and combination therapy with stem cells and medicine, such as cytokines or trophic factors. Finally, the National Institutes of Health guidelines for human stem cell research, clinical trials of commercialized stem cells without larger animal testing, and prohibition of medical tourism were big controversial issues that led to heated discussion.

  5. Lessons from developmental biology for regenerative medicine.

    PubMed

    Turner, Neill J; Keane, Timothy J; Badylak, Stephen F

    2013-09-01

    The ultimate goal of regenerative medicine is the functional restoration of lost or damaged tissues and organs. Since most tissues in man lack true regenerative properties and instead respond to injury with an inflammatory response and scar tissue formation, regenerative medicine strategies that include combinations of cells, scaffolds, and bioactive molecules to replace injured or missing tissues have been developed. The physical, chemical, and electrical cues that define the microenvironmental niche and the effect of these influences upon cell behavior during development are of interest to developmental biologists, with obvious overlap to the interest of the regenerative medicine field. This manuscript provides an overview of current approaches for tissue restoration being investigated in the field of regenerative medicine and attempts to identify areas of mutual beneficial interest with the field of developmental biology.

  6. Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine.

    PubMed

    Bishop, Corey J; Kim, Jayoung; Green, Jordan J

    2014-07-01

    To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.

  7. Clinical imaging in regenerative medicine

    PubMed Central

    Naumova, Anna V; Modo, Michel; Moore, Anna; Murry, Charles E; Frank, Joseph A

    2014-01-01

    In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring. PMID:25093889

  8. Regenerative medicine applications in combat casualty care.

    PubMed

    Fleming, Mark E; Bharmal, Husain; Valerio, Ian

    2014-03-01

    The purpose of this report is to describe regenerative medicine applications in the management of complex injuries sustained by service members injured in support of the wars in Afghanistan and Iraq. Improvements in body armor, resuscitative techniques and faster transport have translated into increased patient survivability and more complex wounds. Combat-related blast injuries have resulted in multiple extremity injuries, significant tissue loss and amputations. Due to the limited availability and morbidity associated with autologous tissue donor sites, the introduction of regenerative medicine has been critical in managing war extremity injuries with composite massive tissue loss. Through case reports and clinical images, this report reviews the application of regenerative medicine modalities employed to manage combat-related injuries. It illustrates that the novel use of hybrid reconstructions combining traditional and regenerative medicine approaches are an effective tool in managing wounds. Lessons learned can be adapted to civilian care.

  9. Regenerative medicine: a primer for paediatricians.

    PubMed

    Polak, Dame Julia M

    2009-11-01

    Regenerative medicine is a multidisciplinary field concerned with the replacement, repair or restoration of injured tissues. Cell therapy and tissue engineering are part of the broader remit of regenerative medicine. The ultimate aim is to provide safe and efficient therapies for a large number of clinical conditions. Novel regenerative therapies are already in use in initial clinical trials. The main components of regenerative medicine are cells and specially designed materials. A vast variety of cells types are currently used including: adult and stem cells. Equally a large number of natural and man-made materials have been investigated. Despite of considerable advances many challenges lie ahead. These are summarised in this review article. The field is slowly maturing and the initial unhelpful hype has been replaced by a more measured, mature and realistic outlook.

  10. Functional imaging for regenerative medicine.

    PubMed

    Leahy, Martin; Thompson, Kerry; Zafar, Haroon; Alexandrov, Sergey; Foley, Mark; O'Flatharta, Cathal; Dockery, Peter

    2016-04-19

    In vivo imaging is a platform technology with the power to put function in its natural structural context. With the drive to translate stem cell therapies into pre-clinical and clinical trials, early selection of the right imaging techniques is paramount to success. There are many instances in regenerative medicine where the biological, biochemical, and biomechanical mechanisms behind the proposed function of stem cell therapies can be elucidated by appropriate imaging. Imaging techniques can be divided according to whether labels are used and as to whether the imaging can be done in vivo. In vivo human imaging places additional restrictions on the imaging tools that can be used. Microscopies and nanoscopies, especially those requiring fluorescent markers, have made an extraordinary impact on discovery at the molecular and cellular level, but due to their very limited ability to focus in the scattering tissues encountered for in vivo applications they are largely confined to superficial imaging applications in research laboratories. Nanoscopy, which has tremendous benefits in resolution, is limited to the near-field (e.g. near-field scanning optical microscope (NSNOM)) or to very high light intensity (e.g. stimulated emission depletion (STED)) or to slow stochastic events (photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM)). In all cases, nanoscopy is limited to very superficial applications. Imaging depth may be increased using multiphoton or coherence gating tricks. Scattering dominates the limitation on imaging depth in most tissues and this can be mitigated by the application of optical clearing techniques that can impose mild (e.g. topical application of glycerol) or severe (e.g. CLARITY) changes to the tissue to be imaged. Progression of therapies through to clinical trials requires some thought as to the imaging and sensing modalities that should be used. Smoother progression is facilitated by the use of

  11. Regenerative medicine: Current therapies and future directions

    PubMed Central

    Mao, Angelo S.; Mooney, David J.

    2015-01-01

    Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies. PMID:26598661

  12. Regenerative Medicine and Stem Cells in Dermatology.

    PubMed

    Moioli, Eduardo K; Bolotin, Diana; Alam, Murad

    2017-05-01

    Clinically relevant regenerative medicine is still in its early stages of development. Difficulties in regenerating large-scale and complex structures, the lack of safety data, and the paucity of clinical trials have slowed the process of technological advance. To familiarize the clinician with techniques available in the laboratory and experimental approaches being tested clinically. In addition, a layout is discussed for how dermatologists can lead the way in bringing regenerative medicine to clinical reality. This article reviews the relevant literature on regenerative medicine for dermatological applications and discusses findings and techniques in a clinically relevant context. Multiple cell-free and cell-based approaches for regenerating dermatologic tissues have been reported in the basic science and clinical literature. These are reviewed in the order of complexity. Incremental steps are needed to apply the principles of regenerative medicine to simple medical problems first. Such a stepwise approach would commence, for example, with creation of single-function tissues that could fill soft-tissue defects and proceed to the development of fully functional skin grafts. Likewise, cell-free approaches can build the foundation for the more technically demanding cell-based strategies that are likely necessary for achieving the ultimate goal of regenerative dermatology.

  13. Regenerative Medicine for Battlefield Injuries

    DTIC Science & Technology

    2012-10-01

    that stimulate cartilage reeneraton across a critical size defect (CSD) in a long bone, using the axolotl , Abystoma mexicanum as a model system...of this scaffold was the right one. Experiments grafting axolotl cartilage and muscle to Xenopus tarsal CSDs indicate that the tissues enhance...regenerative response. 15. SUBJECT TERMS- Axolotl hindlimb model, fibula, temporal characterization of fracture repair, characterization of repair of

  14. Global strategic partnerships in regenerative medicine.

    PubMed

    French, Anna; Suh, Jane Y; Suh, Carol Y; Rubin, Lee; Barker, Richard; Bure, Kim; Reeve, Brock; Brindley, David A

    2014-09-01

    The approach to research and development in biomedical science is changing. Increasingly, academia and industry seek to collaborate, and share resources and expertise, by establishing partnerships. Here, we explore the co-development partnership landscape in the field of regenerative medicine, focusing on agreements involving one or more private entities. A majority of the largest biopharmaceutical companies have announced strategic partnerships with a specific regenerative medicine focus, signifying the growth and widening appeal of this emerging sector. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

    Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

  16. New tools in regenerative medicine: gene therapy.

    PubMed

    Muñoz Ruiz, Miguel; Regueiro, José R

    2012-01-01

    Gene therapy aims to transfer genetic material into cells to provide them with new functions. A gene transfer agent has to be safe, capable of expressing the desired gene for a sustained period of time in a sufficiently large population of cells to produce a biological effect. Identifying a gene transfer tool that meets all of these criteria has proven to be a difficult objective. Viral and nonviral vectors, in vivo, ex vivo and in situ strategies co-exist at present, although ex vivo lenti-or retroviral vectors are presently the most popular.Natural stem cells (from embryonic, hematopoietic, mesenchymal, or adult tissues) or induced progenitor stem (iPS) cells can be modified by gene therapy for use in regenerative medicine. Among them, hematopoietic stem cells have shown clear clinical benefit, but iPS cells hold humongous potential with no ethical concerns.

  17. Insurance systems and reimbursement concerning research and development of regenerative medicine in Japan.

    PubMed

    Okada, Kiyoshi; Miyata, Toshio; Sawa, Yoshiki

    2017-03-01

    In Japan, the Act on the Safety of Regenerative Medicine and the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act were enacted in November 2014, creating a new framework for clinical research and products related to regenerative medicine. Together with these regulatory frameworks, new insurance procedures were created for handling regenerative medicine in Japan. For developing regenerative medicine in Japan, understanding medical insurance greatly influences funding and venture success, particularly in the stages between clinical research and market launch. The study aimed to identify the issues and examples surrounding Japan's present medical insurance system, especially for regenerative medicine. We believe that building stronger insurance systems for regenerative medicine is essential for internationally aligning and harmonizing the progress of regenerative medicine.

  18. [Chondrocytes application in regenerative medicine].

    PubMed

    Dziedzic, Katarzyna; Zalewski, Mateusz; Gadek, Artur; Drukała, Justyna

    2014-01-01

    Cartilage reconstruction is a crucial issue for tissue engineering because of high damage frequency in connection with low regenerative capacity. Microfractures and shaving are the oldest and most commonly used practices. The newest techniques are: Autologous Chondrocyte Implantation, Matrix Associated Chondrocytes Implantation and their derivatives. Dedifferentiation of chondrocytes due to low proliferation rate and phenotype loss makes isolation and in vitro culture of normal human chondrocytes very complex. Therefore, obtaining mesenchymal stem cells from various sources and differentiating them into chondrocytes is another interesting approach.

  19. Why regenerative medicine needs an extracellular matrix.

    PubMed

    Prestwich, Glenn D; Healy, Kevin E

    2015-01-01

    Regenerative medicine is now coming of age. Many attempts at cell therapy have failed to show significant efficacy, and the umbrella term 'stem cell therapy' is perceived in some quarters as hype or just expensive and unnecessary medical tourism. Here we present a short editorial in three parts. First, we examine the importance of using a semisynthetic extracellular matrix (ECM) mimetic, or sECM, to deliver and retain therapeutic cells at the site of administration. Second, we describe one approach in which biophysical and biochemical properties are tailored to each tissue type, which we call "design for optimal functionality." Third, we describe an alternative approach to sECM design and implementation, called "design for simplicity," in which a deconstructed, minimalist sECM is employed and biology is allowed to perform the customization in situ. We opine that an sECM, whether minimal or instructive, is an essential contributor to improve the outcomes of cell-based therapies.

  20. Therapeutic potential of nanoceria in regenerative medicine

    SciTech Connect

    Das, Soumen; Chigurupati, Srinivasulu; Dowding, Janet; Munusamy, Prabhakaran; Baer, Donald R.; McGinnis, James F.; Mattson, Mark P.; Self, William; Seal, Sudipta

    2014-11-01

    Tissue engineering and regenerative medicine aim to achieve functional restoration of tissue or cells damaged through disease, aging or trauma. Advancement of tissue engineering requires innovation in the field of 3D scaffolding, and functionalization with bioactive molecules. Nanotechnology offers advanced materials with patterned nano-morphologies for cell growth and different molecular substrates which can support cell survival and functions. Cerium oxide nanoparticles (nanoceria) can control intracellular as well as extracellular reactive oxygen and nitrogen species. Recent findings suggest that nanoceria can enhance long-term cell survival, enable cell migration and proliferation, and promote stem cell differentiation. Moreover, the self-regenerative property of nanoceria permits a small dose to remain catalytically active for extended time. This review summarizes the possibilities and applications of nanoceria in the field of tissue engineering and regenerative medicine.

  1. [Regenerative medicine in head and neck reconstructive surgery].

    PubMed

    Riedel, F; Goessler, U R; Stern-Straeter, J; Riedel, K; Hörmann, K

    2008-03-01

    Autologous transplantation is regarded as the gold standard in the treatment of congenital or acquired deformities. However, the availability of autologous tissue for transplantation is often limited. Regenerative medicine aims to activate individuals' own intrinsic regenerative mechanisms and embraces tissue engineering, cell/system biology, gene therapy and stem-cell biology. Most approaches in tissue engineering are based on the expansion of small autologous cell aggregates. Tissue engineering supplemented by isolated and amplified stem cells is another very promising option for producing autologous transplants and getting over the limited availability. The association of stem cell-based tissue engineering and gene therapy allows the creation of regenerative tissue in the optimal ambience of regulatory proteins. This leads to great opportunities in the transplantation of skin, bones or cartilage. This paper presents the current status and the possible benefits, but also the limitations, of regenerative medicine in reconstructive surgery of the head and neck.

  2. Expanding horizons of cellular plasticity in regenerative medicine.

    PubMed

    Sen, Chandan K

    2015-10-01

    This Guest Editorial introduces the Regenerative Medicine Theme Issue, which provides critical insight into the unfolding frontier of regenerative medicine. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Mesenchymal stem cells, aging and regenerative medicine

    PubMed Central

    Raggi, Chiara; Berardi, Anna C.

    2012-01-01

    Summary Tissue maintenance and regeneration is dependent on stem cells and increasing evidence has shown to decline with age. Stem cell based-aging is thought to influence therapeutic efficacy. Mesenchymal stromal cells (MSCs) are involved in tissue regeneration. Here, we discuss the effects of age-related changes on MSC properties considering their possible use in research or regenerative medicine. PMID:23738303

  4. Stem cells in regenerative medicine: introduction.

    PubMed

    Ilic, Dusko; Polak, Julia M

    2011-01-01

    Considerable amount of information about the potential of stem cell therapy in regenerative medicine is available today. Scientific meetings and publications in specialized journals enable experts in stem cell science and regenerative medicine to follow worldwide cutting-edge research. However, controversial information plaguing the media and the Internet lead patients to believe that stem cells are the long-awaited panacea even though there are little or no stringent factual data available yet. PubMed database systematically searched in the period 4-6 January 2011. Stem cell-based therapy is a future of regenerative medicine. Based on unsubstantial claims fueled by media, patients are frequently seeking advice about the risks and prospects of specific therapeutic regimes from their physicians. Reports in specialized journals written in a scientific vocabulary are difficult to evaluate for many primary-care physicians. Hence, physicians are reluctant to provide advice or endorse treatment options for cell-based therapies. AREAS TIMELY FOR FURTHER DEVELOPMENT: We wish to fill the gap and offer physicians suitable guidance. By giving a comprehensive overview of different types of stem cells and their potential in a simple language, here we are introducing a series of articles written by world-renowned experts on regenerative medicine about the current status and prospects of the field from the point of view of the standard level of patient safety and efficacy for the healthcare industry.

  5. Materials science tools for regenerative medicine

    NASA Astrophysics Data System (ADS)

    Richardson, Wade Nicholas

    Regenerative therapies originating from recent technological advances in biology could revolutionize medicine in the coming years. In particular, the advent of human pluripotent stem cells (hPSCs), with their ability to become any cell in the adult body, has opened the door to an entirely new way of treating disease. However, currently these medical breakthroughs remain only a promise. To make them a reality, new tools must be developed to surmount the new technical hurdles that have arisen from dramatic departure from convention that this field represents. The collected work presented in this dissertation covers several projects that seek to apply the skills and knowledge of materials science to this tool synthesizing effort. The work is divided into three chapters. The first deals with our work to apply Raman spectroscopy, a tool widely used for materials characterization, to degeneration in cartilage. We have shown that Raman can effectively distinguish the matrix material of healthy and diseased tissue. The second area of work covered is the development of a new confocal image analysis for studying hPSC colonies that are chemical confined to uniform growth regions. This tool has important application in understanding the heterogeneity that may slow the development of hPSC -based treatment, as well as the use of such confinement in the eventually large-scale manufacture of hPSCs for therapeutic use. Third, the use of structural templating in tissue engineering scaffolds is detailed. We have utilized templating to tailor scaffold structures for engineering of constructs mimicking two tissues: cartilage and lung. The work described here represents several important early steps towards large goals in regenerative medicine. These tools show a great deal of potential for accelerating progress in this field that seems on the cusp of helping a great many people with otherwise incurable disease.

  6. Regenerative medicine and stem cell based drug discovery.

    PubMed

    Sakurada, Kazuhiro; McDonald, Fiona M; Shimada, Fumiki

    2008-01-01

    As William Shakespeare beautifully described, increasing age often causes loss of tissue and organ function. The increase in average life expectancy in many countries is generating an aging society and an increase in age-related health problems. Regenerative medicine is expected to be a powerful actor in this drama, and stem cell technology may hold the key to the development of innovative treatments for acute and chronic degenerative conditions. This Review surveys the present situation and some future prospects for regenerative medicine and stem cell based drug discovery.

  7. Common ethical issues in regenerative medicine.

    PubMed

    Awaya, Tsuyoshi

    2005-01-01

    One of the common ethical issues in regenerative medicine is progress in 'componentation' (= being treated as parts) of the human body, and the enhancement of the view of such "human body parts." 'Componentation' of the human body represents a preliminary step toward commodification of the human body. The process of commodification of the human body follows the steps of 'materialization' (= being treated as a material object) [first step] -- 'componentation' [second step] -- 'resourcialization' (= being treated as resources) [third step] -- commodification [fourth step]. Transplantation medicine and artificial organ developments have dramatically exposed the potential of organs and tissues as parts, and regenerative medicine has a role in advancing 'componentation' of the human body and further enhancing the view of human body parts. The 'componentation' of the human body, regardless of the degree of regenerative medicine's contribution to it, is considered as a challenge to the traditional view of human bodies and the abstract value of "Human Dignity" in the same way or alongside the 'resourcialization' and commodification. However, in the future, a new perspective of human bodies that means "a perspective whereby human bodies, organs, tissues, and even the bodies themselves are perceived as disposable tools like disposable cameras, syringes, or contact lens" and therefore a new ethical view, suitable for a new reality, may emerge.

  8. DDS for anti-aging and regenerative medicine (review).

    PubMed

    Mizushima, Y; Hoshi, K

    2006-01-01

    In this paper we summarized, first the present status and history of the development of research in anti-aging and regenerative medicine in Japan, and secondly some of our research using DDS in the field of both medicine. The regenerative medicine has been developed in Japan by using the fund from the Government, particularly as the Millennium Project. While anti-aging medicine developed following the social interest on it in Japan and it was influenced by American Society (A4M). Next, we summarized our research on DDS for anti-aging and regenerative medicine. In most cases we used oily or solid nanoparticles as carriers of drug. Those particles have a property of both of targeting and slow release in the DDS technology. The two properties are important for anti-aging and regenerative medicine, since drugs have to be administered safely and for long time. We applied prostaglandin E1, granulocyte-colony stimulate factor (G-CSF), and retinoid into the systems.

  9. Regenerative medicine: does Erythropoietin have a role?

    PubMed

    Buemi, Michele; Lacquaniti, Antonio; Maricchiolo, Giulia; Bolignano, Davide; Campo, Susanna; Cernaro, Valeria; Sturiale, Alessio; Grasso, Giovanni; Buemi, Antoine; Allegra, Alessandro; Donato, Valentina; Genovese, Lucrezia

    2009-01-01

    Regenerative Medicine, a recent new medical domain, aims to develop new therapies through the stimulation of natural regenerative processes also in human beings. In this field, Erythropoietin (EPO) represents a significant subject of research. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on the central nervous system, cardiovascular system and renal tissue. This action is carried out through one of few regenerative activities of human beings: angiogenesis. This mechanism, which involves endothelial stem cells and VEGF (Vascular Endothelial Growth Factor), has been experimentally demonstrated with Recombinant human erythropoietin (rHuEPO) and Darbepoetin, a long-acting EPO derivate. Furthermore, the demonstration of a cardiac production of EPO in Fugu rubripes and in Zebrafish has led cardiologists to "discover" Erythropoietin, postulating a hypothetical role in treatment of cardiovascular disease for this hormone. This is some of the experimental evidence which demonstrates that EPO can be in reason considered an important element of research of Regenerative Medicine and put in the network of drugs able to regenerate tissues and organs.

  10. Fluorescent Cell Imaging in Regenerative Medicine

    PubMed Central

    Sapoznik, Etai; Niu, Guoguang; Zhou, Yu; Murphy, Sean V.; Soker, Shay

    2016-01-01

    Fluorescent protein imaging, a promising tool in biological research, incorporates numerous applications that can be of specific use in the field of regenerative medicine. To enhance tissue regeneration efforts, scientists have been developing new ways to monitor tissue development and maturation in vitro and in vivo. To that end, new imaging tools and novel fluorescent proteins have been developed for the purpose of performing deep-tissue high-resolution imaging. These new methods, such as intra-vital microscopy and Förster resonance energy transfer, are providing new insights into cellular behavior, including cell migration, morphology, and phenotypic changes in a dynamic environment. Such applications, combined with multimodal imaging, significantly expand the utility of fluorescent protein imaging in research and clinical applications of regenerative medicine. PMID:27158228

  11. Electrospun Silk Biomaterial Scaffolds for Regenerative Medicine

    PubMed Central

    Zhang, Xiaohui; Reagan, Michaela R; Kaplan, David L.

    2009-01-01

    Electrospinning is a versatile technique that enables the development of nanofiber-based biomaterial scaffolds. Scaffolds can be generated that are useful for tissue engineering and regenerative medicine since they mimic the nanoscale properties of certain fibrous components of the native extracellular matrix in tissues. Silk is a natural protein with excellent biocompatibility, remarkable mechanical properties as well as tailorable degradability. Integrating these protein polymer advantages with electrospinning results in scaffolds with combined biochemical, topographical and mechanical cues with versatility for a range of biomaterial, cell and tissue studies and applications. This review covers research related to electrospinning of silk, including process parameters, post treatment of the spun fibers, functionalization of nanofibers, and the potential applications for these material systems in regenerative medicine. Research challenges and future trends are also discussed. PMID:19643154

  12. [Progress in stem cells and regenerative medicine].

    PubMed

    Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

    2015-06-01

    Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

  13. Induced pluripotent stem cells for regenerative medicine.

    PubMed

    Hirschi, Karen K; Li, Song; Roy, Krishnendu

    2014-07-11

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.

  14. Chemical transdifferentiation: closer to regenerative medicine.

    PubMed

    Xu, Aining; Cheng, Lin

    2016-06-01

    Cell transdifferentiation, which directly switches one type of differentiated cells into another cell type, is more advantageous than cell reprogramming to generate pluripotent cells and differentiate them into functional cells. This process is crucial in regenerative medicine. However, the cell-converting strategies, which mainly depend on the virus-mediated expression of exogenous genes, have clinical safety concerns. Small molecules with compelling advantages are a potential alternative in manipulating cell fate conversion. In this review, we briefly retrospect the nature of cell transdifferentiation and summarize the current developments in the research of small molecules in promoting cell conversion. Particularly, we focus on the complete chemical compound-induced cell transdifferentiation, which is closer to the clinical translation in cell therapy. Despite these achievements, the mechanisms underpinning chemical transdifferentiation remain largely unknown. More importantly, identifying drugs that induce resident cell conversion in vivo to repair damaged tissue remains to be the end-goal in current regenerative medicine.

  15. Regenerative medicine solutions in congenital diaphragmatic hernia.

    PubMed

    De Coppi, Paolo; Deprest, Jan

    2017-06-01

    Congenital diaphragmatic hernia (CDH) remains a major challenge and associated mortality is still significant. Patients have benefited from current therapeutic options, but most severe cases are still associated to poor outcome. Regenerative medicine is emerging as a valid option in many diseases and clinical trials are currently happening for various conditions in children and adults. We report here the advancement in the field which will help both in the understanding of further CDH development and in offering new treatment options for the difficult situations such as repair of large diaphragmatic defects and lung hypoplasia. The authors believe that advancements in regenerative medicine may lead to increase of CDH patients׳ survival. Copyright © 2017. Published by Elsevier Inc.

  16. Induced Pluripotent Stem Cells for Regenerative Medicine

    PubMed Central

    Hirschi, Karen K.; Li, Song; Roy, Krishnendu

    2014-01-01

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine. PMID:24905879

  17. Regenerative medicine. The industry comes of age.

    PubMed

    Mason, C

    2007-01-01

    The regenerative medicine industry has moved into a new era in which commercialisation and not research is the number one priority. To achieve its new goal, much has had to change, including the introduction of expert business management, simpler but superior products and scalability of manufacture. Mass public and political support is supplying both long-term resources and the market demand to finally create a sustainable new health-care sector.

  18. Upconversion Nanoparticles for Bioimaging and Regenerative Medicine

    PubMed Central

    González-Béjar, María; Francés-Soriano, Laura; Pérez-Prieto, Julia

    2016-01-01

    Nanomaterials are proving useful for regenerative medicine in combination with stem cell therapy. Nanoparticles (NPs) can be administrated and targeted to desired tissues or organs and subsequently be used in non-invasive real-time visualization and tracking of cells by means of different imaging techniques, can act as therapeutic agent nanocarriers, and can also serve as scaffolds to guide the growth of new tissue. NPs can be of different chemical nature, such as gold, iron oxide, cadmium selenide, and carbon, and have the potential to be used in regenerative medicine. However, there are still many issues to be solved, such as toxicity, stability, and resident time. Upconversion NPs have relevant properties such as (i) low toxicity, (ii) capability to absorb light in an optical region where absorption in tissues is minimal and penetration is optimal (note they can also be designed to emit in the near-infrared region), and (iii) they can be used in multiplexing and multimodal imaging. An overview on the potentiality of upconversion materials in regenerative medicine is given. PMID:27379231

  19. Congenital anomalies of soft tissues: birth defects depending on tissue engineering solutions and present advances in regenerative medicine.

    PubMed

    Saxena, Amulya K

    2010-10-01

    Congenital anomalies encompass a wide range of malformations that could affect various organs and tissues in the newborn and infant population. These disorders that involve defects in or injury to a developing fetus may be a result of genetic abnormalities or mutations, alterations in the intrauterine environment, irregularities in morphogenesis, or chromosomal aberration. The outcome of these defects could lead to minor anomalies or major malformations that are dependent on the complex processes between the prenatal deficit and postnatal environment. Often multiple malformations occur within the same fetus and give rise to a malformation syndrome. Since congenital anomalies are evident at birth, solutions must be found to improve the clinical state and quality of life that a newborn has to lead from infancy through adolescence into adulthood. Transplantation options in this age group are limited due to the shortage of organs and the discrepancy in adult donor size mismatch. Over the past 2 decades tremendous strides have been made in the research of biomaterials, stem cells, organ generation, and tissue engineering to provide viable solutions to a wide range of organ and tissue losses focusing on the adult population. This review intends to highlight the shortage of tissue and organs in neonates and infants with congenital malformations. This is also the first monograph that presents estimation of incidences of the congenital malformations based on an extensive literature search. It also outlines the challenges in clinical management of these entities and presents an organ-based demand for engineered tissues.

  20. Airway transplantation: a challenge for regenerative medicine.

    PubMed

    Martinod, Emmanuel; Seguin, Agathe; Radu, Dana M; Boddaert, Guillaume; Chouahnia, Kader; Fialaire-Legendre, Anne; Dutau, Hervé; Vénissac, Nicolas; Marquette, Charles-Hugo; Baillard, Christophe; Valeyre, Dominique; Carpentier, Alain

    2013-07-29

    After more than 50 years of research, airway transplantation remains a major challenge in the fields of thoracic surgery and regenerative medicine. Five principal types of tracheobronchial substitutes, including synthetic prostheses, bioprostheses, allografts, autografts and bioengineered conduits have been evaluated experimentally in numerous studies. However, none of these works have provided a standardized technique for the replacement of the airways. More recently, few clinical attempts have offered encouraging results with ex vivo or stem cell-based engineered airways and tracheal allografts implanted after heterotopic revascularization. In 1997, we proposed a novel approach: the use of aortic grafts as a biological matrix for extensive airway reconstruction. In vivo regeneration of epithelium and cartilage were demonstrated in animal models. This led to the first human applications using cryopreserved aortic allografts that present key advantages because they are available in tissue banks and do not require immunosuppressive therapy. Favorable results obtained in pioneering cases have to be confirmed in larger series of patients with extensive tracheobronchial diseases.

  1. REGENERATIVE MEDICINE AS APPLIED TO GENERAL SURGERY

    PubMed Central

    Orlando, Giuseppe; Wood, Kathryn J; De Coppi, Paolo; Baptista, Pedro M; Binder, Kyle W; Bitar, Khalil N; Breuer, Christopher; Burnett, Luke; Christ, George; Farney, Alan; Figliuzzi, Marina; Holmes, James H; Koch, Kenneth; Macchiarini, Paolo; Sani, Sayed-Hadi Mirmalek; Opara, Emmanuel; Remuzzi, Andrea; Rogers, Jeffrey; Saul, Justin M; Seliktar, Dror; Shapira-Schweitzer, Keren; Smith, Tom; Solomon, Daniel; Van Dyke, Mark; Yoo, James J; Zhang, Yuanyuan; Atala, Anthony; Stratta, Robert J; Soker, Shay

    2012-01-01

    The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues or organs in order to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate. PMID:22330032

  2. Regenerative medicine as applied to general surgery.

    PubMed

    Orlando, Giuseppe; Wood, Kathryn J; De Coppi, Paolo; Baptista, Pedro M; Binder, Kyle W; Bitar, Khalil N; Breuer, Christopher; Burnett, Luke; Christ, George; Farney, Alan; Figliuzzi, Marina; Holmes, James H; Koch, Kenneth; Macchiarini, Paolo; Mirmalek Sani, Sayed-Hadi; Opara, Emmanuel; Remuzzi, Andrea; Rogers, Jeffrey; Saul, Justin M; Seliktar, Dror; Shapira-Schweitzer, Keren; Smith, Tom; Solomon, Daniel; Van Dyke, Mark; Yoo, James J; Zhang, Yuanyuan; Atala, Anthony; Stratta, Robert J; Soker, Shay

    2012-05-01

    The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate.

  3. Endometrial stem cells in regenerative medicine.

    PubMed

    Verdi, Javad; Tan, Aaron; Shoae-Hassani, Alireza; Seifalian, Alexander M

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo.

  4. Endometrial stem cells in regenerative medicine

    PubMed Central

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo. PMID:25097665

  5. Bioethical aspects of regenerative and reproductive medicine.

    PubMed

    Yoshimura, Yasunori

    2006-05-01

    The birth announced in 1997 of Dolly, the lamb cloned from the somatic mammary cells of an adult ewe, and the discovery of human embryonic stem cells in 1998 have been the most exciting developments in the biological sciences in the past decade. Reproductive somatic cell nuclear transfer (SCNT) in additional species has been inefficient in that relatively few births, harmful side effects and high fetal and neonatal death rates have resulted from many attempts. Ongoing debates about the ethics of reproductive SCNT have revealed that some researchers regard human reproductive SCNT as morally unacceptable in all circumstances, others see merit in reproductive SCNT in certain circumstances and others await more information before making judgment about the ethical status of the procedure. Regenerative medicine and emerging biotechnologies started to revolutionize the practice of medicine. Advances in stem cell biology, including embryonic and postnatal somatic stem cells, have made the prospect of tissue regeneration a potential reality. Mammal cloning experiments have provided new impetus to the prospect of regenerative medicine through stem cell research. The procedure of SCNT could be used to create the raw material to replace defective or senescent tissue as a natural extension of the biology of stem cells. Researchers working in reproductive medicine should consider the potential hope given to many patients against the requisite and ethically contentious creation of human blastocysts for therapeutic intent.

  6. New glossary of terms used in regenerative medicine: standardization continues to emerge as regenerative medicine matures.

    PubMed

    Sheridan, Ben; Harris, Neil

    2009-07-01

    Regenerative medicine is an evolving, cross-disciplinary, international field that, as a result, uses terms that are either not widely understood, or may have a number of different meanings. Many stakeholders have identified this lack of clarity as a potential barrier to effective communication within the field. To address this, BSI British Standards, supported by the UK Department for Innovation, Universities and Skills (DIUS), was commissioned to develop guidance on the definitions of terms used within regenerative medicine. The resulting document aims to provide clear consensus terminology to improve communication and facilitate a common understanding for a broad range of potential users.

  7. TOPICAL REVIEW: Cell and biomolecule delivery for regenerative medicine

    NASA Astrophysics Data System (ADS)

    Smith, Ian O.; Ma, Peter X.

    2010-02-01

    Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell-material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine.

  8. The international translational regenerative medicine center.

    PubMed

    Alexis, Mardi de Veuve; Grinnemo, Karl-Henrik; Jove, Richard

    2012-11-01

    The International Translational Regenerative Medicine Center, an organizing sponsor of the World Stem Cell Summit 2012, is a global initiative established in 2011 by founding partners Karolinska Institutet (Stockholm, Sweden) and Beckman Research Institute at City of Hope (CA, USA) with a mission to facilitate the acceleration of translational research and medicine on a global scale. Karolinska Institutet, home of the Nobel Prize in Medicine or Physiology, is one of the most prestigious medical research institutions in the world. The Beckman Research Institute/City of Hope is ranked among the leading NIH-designated comprehensive cancer research and treatment institutions in the USA, has the largest academic GMP facility and advanced drug discovery capability, and is a pioneer in diabetes research and treatment.

  9. Regulating the therapeutic translation of regenerative medicine.

    PubMed

    Cuchiara, Maude L; Olive, Jackie K; Matthews, Kirstin

    2015-01-01

    Regenerative medicine and stem cell research are exciting new fields. But as the fields progress toward clinical therapies, controversies emerge. Hype surrounding stem cell research has caused an increase in their use in interventions that are not clinically proven. Furthermore, the regulatory agencies have a lot of difficulty dealing with cell therapies, which are distinctly different from drugs and medical devices they more commonly approve. To move the field forward, advocates, regulators and scientists need to come together to find new options for stem cell research oversight that protects both the patients and the research field.

  10. Phosphorous-Containing Polymers for Regenerative Medicine

    PubMed Central

    Watson, Brendan M.; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    Disease and injury have resulted in a large, unmet need for functional tissue replacements. Polymeric scaffolds can be used to deliver cells and bioactive signals to address this need for regenerating damaged tissue. Phosphorous-containing polymers have been implemented to improve and accelerate the formation of native tissue both by mimicking the native role of phosphorous groups in the body and by attachment of other bioactive molecules. This manuscript reviews the synthesis, properties, and performance of phosphorous-containing polymers that can be useful in regenerative medicine applications. PMID:24565855

  11. The essential materials paradigms for regenerative medicine

    NASA Astrophysics Data System (ADS)

    Williams, David

    2011-04-01

    Medical technology is changing rapidly. Several disease states can now be treated very effectively by implantable devices that restore mechanical and physical functionality, such as replacement of hip joints or restoration of heart rhythms by pacemakers. These techniques, however, are rather limited, and no biological functionality can be restored through the use of inert materials and devices. This paper explores the role of new types of biomaterials within the emerging area of regenerative medicine, where they are able to play a powerful role in persuading the human body to regenerate itself.

  12. Collagen: a network for regenerative medicine

    PubMed Central

    Pawelec, K. M.; Best, S. M.

    2016-01-01

    The basic building block of the extra-cellular matrix in native tissue is collagen. As a structural protein, collagen has an inherent biocompatibility making it an ideal material for regenerative medicine. Cellular response, mediated by integrins, is dictated by the structure and chemistry of the collagen fibers. Fiber formation, via fibrillogenesis, can be controlled in vitro by several factors: pH, ionic strength, and collagen structure. After formation, fibers are stabilized via cross-linking. The final bioactivity of collagen scaffolds is a result of both processes. By considering each step of fabrication, scaffolds can be tailored for the specific needs of each tissue, improving their therapeutic potential. PMID:27928505

  13. Engineering growth factors for regenerative medicine applications.

    SciTech Connect

    Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.; Cochran, Jennifer R.

    2016-01-15

    Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications.

  14. Repairing quite swimmingly: advances in regenerative medicine using zebrafish

    PubMed Central

    Goessling, Wolfram; North, Trista E.

    2014-01-01

    Regenerative medicine has the promise to alleviate morbidity and mortality caused by organ dysfunction, longstanding injury and trauma. Although regenerative approaches for a few diseases have been highly successful, some organs either do not regenerate well or have no current treatment approach to harness their intrinsic regenerative potential. In this Review, we describe the modeling of human disease and tissue repair in zebrafish, through the discovery of disease-causing genes using classical forward-genetic screens and by modulating clinically relevant phenotypes through chemical genetic screening approaches. Furthermore, we present an overview of those organ systems that regenerate well in zebrafish in contrast to mammalian tissue, as well as those organs in which the regenerative potential is conserved from fish to mammals, enabling drug discovery in preclinical disease-relevant models. We provide two examples from our own work in which the clinical translation of zebrafish findings is either imminent or has already proven successful. The promising results in multiple organs suggest that further insight into regenerative mechanisms and novel clinically relevant therapeutic approaches will emerge from zebrafish research in the future. PMID:24973747

  15. Stem cells: intellectual property issues in regenerative medicine.

    PubMed

    Zachariades, Nicholas A

    2013-12-01

    The topic of stem cells for use in regenerative medicine, especially embryonic stem cells, inspires much debate, discussion, and outrage as it slices through the very core moral values of society. These social and moral issues have, in turn, resulted in government policies that have influenced the study of stem cells in regenerative medicine.

  16. Regenerative medicine. Opportunities and challenges: a brief overview.

    PubMed

    Polak, Dame Julia

    2010-12-06

    Regenerative medicine is a new multi-disciplinary field aiming at the repair or replacement of disease body parts. The field is progressing at an unprecedented pace and although the opportunities are immense, many hurdles lie ahead. This brief review analyses the opportunities and challenges faced by regenerative medicine.

  17. Carbohydrate engineered cells for regenerative medicine.

    PubMed

    Du, Jian; Yarema, Kevin J

    2010-06-15

    Carbohydrates are integral components of the stem cell niche on several levels; proteoglycans are a major constituent of the extracellular matrix (ECM) surrounding a cell, glycosoaminoglycans (GAGs) help link cells to the ECM and the neighboring cells, and small but informationally-rich oligosaccharides provide a "sugar code" that identifies each cell and provides it with unique functions. This article samples roles that glycans play in development and then describes how metabolic glycoengineering - a technique where monosaccharide analogs are introduced into the metabolic pathways of a cell and are biosynthetically incorporated into the glycocalyx - is overcoming many of the long-standing barriers to manipulating carbohydrates in living cells and tissues and is becoming an intriguing new tool for tissue engineering and regenerative medicine.

  18. Carbohydrate Engineered Cells for Regenerative Medicine

    PubMed Central

    Du, Jian; Yarema, Kevin J.

    2010-01-01

    Carbohydrates are integral components of the stem cell niche on several levels; proteoglycans are a major constituent of the extracellular matrix (ECM) surrounding a cell, glycosoaminoglycans (GAGs) help link cells to the ECM and the neighboring cells, and small but informationally-rich oligosaccharides provide a “sugar code” that identifies each cell and provides it with unique functions. This article samples roles that glycans play in development and then describes how metabolic glycoengineering – a technique where monosaccharide analogs are introduced into the metabolic pathways of a cell and are biosynthetically incorporated into the glycocalyx – is overcoming many of the long-standing barriers to manipulating carbohydrates in living cells and tissues and is becoming an intriguing new tool for tissue engineering and regenerative medicine. PMID:20117158

  19. Genetic engineering for skeletal regenerative medicine.

    PubMed

    Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

    2007-01-01

    The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

  20. Regenerative medicine: the emergence of an industry.

    PubMed

    Nerem, Robert M

    2010-12-06

    Over the last quarter of a century there has been an emergence of a tissue engineering industry, one that has now evolved into the broader area of regenerative medicine. There have been 'ups and downs' in this industry; however, it now appears to be on a track that may be described as 'back to the future'. The latest data indicate that for 2007 the private sector activity in the world for this industry is approaching $2.5 billion, with 167 companies/business units and more than 6000 employee full time equivalents. Although small compared with the medical device and also the pharmaceutical industries, these numbers are not insignificant. Thus, there is the indication that this industry, and the related technology, may still achieve its potential and address the needs of millions of patients worldwide, in particular those with needs that currently are unmet.

  1. Liposomes in tissue engineering and regenerative medicine

    PubMed Central

    Monteiro, Nelson; Martins, Albino; Reis, Rui L.; Neves, Nuno M.

    2014-01-01

    Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches. PMID:25401172

  2. Regenerative medicine: implications for craniofacial surgery.

    PubMed

    Schantz, Jan-Thorsten; Machens, Hans-Günther; Schilling, Arndt F; Teoh, Swee-Hin

    2012-03-01

    Craniofacial reconstruction of cases with complex anatomy challenges surgeons. The recently emerging field of tissue engineering and regenerative medicine has resulted in a variety of novel therapeutic concepts particularly in the craniofacial area. However, researchers still face significant problems when translating scientific concepts from the bench to the bedside. Reconstruction procedures depend on sustainability, aesthetic outcome, and functionality. Tissue engineering approaches yield powerful tools for long-term satisfying results enabling customized reconstruction and supporting natural healing processes. In conclusion, further advances of tissue-engineered reconstruction need multidisciplinary research to create complex tissue structures and make satisfactory outcomes clinically achievable for most patients. This review highlights clinical advances in the field and gives an overview about current scientific concepts.

  3. Regenerative medicine: the emergence of an industry

    PubMed Central

    Nerem, Robert M.

    2010-01-01

    Over the last quarter of a century there has been an emergence of a tissue engineering industry, one that has now evolved into the broader area of regenerative medicine. There have been ‘ups and downs’ in this industry; however, it now appears to be on a track that may be described as ‘back to the future’. The latest data indicate that for 2007 the private sector activity in the world for this industry is approaching $2.5 billion, with 167 companies/business units and more than 6000 employee full time equivalents. Although small compared with the medical device and also the pharmaceutical industries, these numbers are not insignificant. Thus, there is the indication that this industry, and the related technology, may still achieve its potential and address the needs of millions of patients worldwide, in particular those with needs that currently are unmet. PMID:20843840

  4. Rejuvenation: an integrated approach to regenerative medicine.

    PubMed

    Kang, Y James; Zheng, Lily

    2013-12-01

    The word "rejuvenate" found in the Merriam-Webster dictionary is (1) to make young or youthful again: give new vigor to, and (2) to restore to an original or new state. Regenerative medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. To accomplish this, approaches including transplantation, tissue engineering, cell therapy, and gene therapy are brought into action. These all use exogenously prepared materials to forcefully mend the failed organ. The adaptation of the materials in the host and their integration into the organ are all uncertain. It is a common sense that tissue injury in the younger is easily repaired and the acute injury is healed better and faster. Why does the elder have a diminished capacity of self-repairing, or why does chronic injury cause the loss of the self-repairing capacity? There must be some critical elements that are involved in the repair process, but are suppressed in the elder or under the chronic injury condition. Rejuvenation of the self-repair mechanism would be an ideal solution for functional recovery of the failed organ. To achieve this, it would involve renewal of the injury signaling, reestablishment of the communication and transportation system, recruitment of the materials for repairing, regeneration of the failed organ, and rehabilitation of the renewed organ. It thus would require a comprehensive understanding of developmental biology and a development of new approaches to activate the critical players to rejuvenate the self-repair mechanism in the elder or under chronic injury condition. Efforts focusing on rejuvenation would expect an alternative, if not a better, accomplishment in the regenerative medicine.

  5. State of the art: stem cells in equine regenerative medicine.

    PubMed

    Lopez, M J; Jarazo, J

    2015-03-01

    According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano- and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no 'one-size-fits-all' regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine.

  6. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    PubMed Central

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

  7. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics.

    PubMed

    Mahla, Ranjeet Singh

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

  8. A review on endogenous regenerative technology in periodontal regenerative medicine.

    PubMed

    Chen, Fa-Ming; Zhang, Jing; Zhang, Min; An, Ying; Chen, Fang; Wu, Zhi-Fen

    2010-11-01

    Periodontitis is a globally prevalent inflammatory disease that causes the destruction of the tooth-supporting apparatus and potentially leads to tooth loss. Currently, the methods to reconstitute lost periodontal structures (i.e. alveolar bone, periodontal ligament, and root cementum) have relied on conventional mechanical, anti-infective modalities followed by a range of regenerative procedures such as guided tissue regeneration, the use of bone replacement grafts and exogenous growth factors (GFs), and recently developed tissue engineering technologies. However, all current or emerging paradigms have either been shown to have limited and variable outcomes or have yet to be developed for clinical use. To accelerate clinical translation, there is an ongoing need to develop therapeutics based on endogenous regenerative technology (ERT), which can stimulate latent self-repair mechanisms in patients and harness the host's innate capacity for regeneration. ERT in periodontics applies the patient's own regenerative 'tools', i.e. patient-derived GFs and fibrin scaffolds, sometimes in association with commercialized products (e.g. Emdogain and Bio-Oss), to create a material niche in an injured site where the progenitor/stem cells from neighboring tissues can be recruited for in situ periodontal regeneration. The choice of materials and the design of implantable devices influence therapeutic potential and the number and invasiveness of the associated clinical procedures. The interplay and optimization of each niche component involved in ERT are particularly important to comprehend how to make the desired cell response safe and effective for therapeutics. In this review, the emerging opportunities and challenges of ERT that avoid the ex vivo culture of autologous cells are addressed in the context of new approaches for engineering or regeneration of functional periodontal tissues by exploiting the use of platelet-rich products and its associated formulations as key

  9. Advancing pig cloning technologies towards application in regenerative medicine.

    PubMed

    Nagashima, H; Matsunari, H; Nakano, K; Watanabe, M; Umeyama, K; Nagaya, M

    2012-08-01

    Regenerative medicine is expected to make a significant contribution by development of novel therapeutic treatments for intractable diseases and for improving the quality of life of patients. Many advances in regenerative medicine, including basic and translational research, have been developed and tested in experimental animals; pigs have played an important role in various aspects of this work. The value of pigs as a model species is being enhanced by the generation of specially designed animals through cloning and genetic modifications, enabling more sophisticated research to be performed and thus accelerating the clinical application of regenerative medicine. This article reviews the significant aspects of the creation and application of cloned and genetically modified pigs in regenerative medicine research and considers the possible future directions of the technology. We also discuss the importance of reproductive biology as an interface between basic science and clinical medicine. © 2012 Blackwell Verlag GmbH.

  10. History of regenerative medicine: looking backwards to move forwards.

    PubMed

    Kemp, Paul

    2006-09-01

    If the song by the international popstar Sting is to be relied upon, 'History will teach us nothing'. At the risk of contradicting a one-time schoolteacher, I believe the reverse is true for regenerative medicine. In fact, I think we dismiss the past at our peril. In this review, I aim to trace the history of regenerative medicine to date. I will examine parallels with other areas of medicine and show how commercial, technical and socio/economic factors have influenced the pace and direction of the sector's evolution. I will discuss how, by learning from the past, those involved in regenerative medicine are reinventing their sector for the better. In conclusion, I will evaluate the current state of the industry, suggest what the future may hold and explain why I believe regenerative medicine is about to 'come of age'.

  11. The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

    2009-01-01

    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

  12. The impact of biomechanics in tissue engineering and regenerative medicine.

    PubMed

    Butler, David L; Goldstein, Steven A; Guldberg, Robert E; Guo, X Edward; Kamm, Roger; Laurencin, Cato T; McIntire, Larry V; Mow, Van C; Nerem, Robert M; Sah, Robert L; Soslowsky, Louis J; Spilker, Robert L; Tranquillo, Robert T

    2009-12-01

    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges.

  13. Advent and maturation of regenerative medicine.

    PubMed

    Mhashilkar, Abner M; Atala, Anthony

    2012-11-01

    The field of regenerative medicine (RM), encompassing stem cell (SC) technologies, therapeutics, tissue engineering (TE), biomaterials, scaffolds and other enabling technologies provides a wide gamut of tools and tracks to combat, manage and hopefully cure serious human and animal injuries, dysfunctions and diseases. This review illustrates the trends that are becoming the major platforms in this field. The last 10 years in itself has seen major definitive observations, including multi-track directives of adult stem cell translational technologies, tissue and organ engineering protocols, iPS cell applications and understanding of the role of cancer stem cells to develop effective anti-cancer regimens. With the rapid advances of RM translational research, further advances are expected to be implemented for personalized repair and curative outcomes. RM future is bright although laden with challenges of global fragmentation which needs coherent consolidation, stringent cost and time effective regulation and long-term funding mechanisms, so clinical and diagnostic solutions are realized and recognized to combat unmet medical needs.

  14. Introduction to stem cells and regenerative medicine.

    PubMed

    Kolios, George; Moodley, Yuben

    2013-01-01

    Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded our understanding of development as well as the pathogenesis of disease. Disease-specific cell lines can also be propagated and used in drug development. Despite the significant advances in stem cell biology, issues such as ethical controversies with embryonic stem cells, tumor formation, and rejection limit their utility. However, many of these limitations are being bypassed and this could lead to major advances in the management of disease. This review is an introduction to the world of stem cells and discusses their definition, origin, and classification, as well as applications of these cells in regenerative medicine.

  15. Regenerative Medicine for Epilepsy: From Basic Research to Clinical Application

    PubMed Central

    Yasuhara, Takao; Agari, Takashi; Kameda, Masahiro; Kondo, Akihiko; Kuramoto, Satoshi; Jing, Meng; Sasaki, Tatsuya; Toyoshima, Atsuhiko; Sasada, Susumu; Sato, Kenichiro; Shinko, Aiko; Wakamori, Takaaki; Okuma, Yu; Miyoshi, Yasuyuki; Tajiri, Naoki; Borlongan, Cesario V.; Date, Isao

    2013-01-01

    Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data. PMID:24287913

  16. Science and Ethics: Bridge to the Future for Regenerative Medicine

    PubMed Central

    Patricio, Ventura-Juncá

    2011-01-01

    The objective of this article is to reflect on the relationship between regenerative medicine and ethics, using as references the Aristotelian concept of what is ethical and that of Raessler Van Potter about bioethics. To do this, I will briefly describe the advances in regenerative medicine with stem cells, the strategies for producing pluripotential cells without destroying human embryos, and the great potential of stem cells to improve life for Humanity, noting that for this to be possible, it is necessary to locate the role of regenerative medicine in the context of human values and well being. In this way, this article has a real perspective of the role that regenerative medicine can play in benefitting human beings and engendering respect for human and natural environments. PMID:24298338

  17. Cell sheet engineering for regenerative medicine: current challenges and strategies.

    PubMed

    Owaki, Toshiyuki; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

    2014-07-01

    Substantial progress made in the areas of stem cell research and regenerative medicine has provided a number of innovative methods to repair or regenerate defective tissues and organs. Although previous studies regarding regenerative medicine, especially those involving induced pluripotent stem cells, have been actively promoted in the past decade, there remain some challenges that need to be addressed in order to enable clinical applications. Designed for use in clinical applications, cell sheet engineering has been developed as a unique, scaffold-free method of cell processing utilizing temperature-responsive cell culture vessels. Clinical studies using cell sheets have shown positive outcomes and will be translated into clinical practice in the near future. However, several challenges stand in the way of the industrialization of cell sheet products and the widespread acceptance of regenerative medicine based on cell sheet engineering. This review describes current strategies geared towards the realization of the regenerative medicine approach.

  18. Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies

    PubMed Central

    Hunsberger, Joshua; Harrysson, Ola; Shirwaiker, Rohan; Starly, Binil; Wysk, Richard; Cohen, Paul; Allickson, Julie; Yoo, James

    2015-01-01

    Summary The Regenerative Medicine Foundation Annual Conference held on May 6 and 7, 2014, had a vision of assisting with translating tissue engineering and regenerative medicine (TERM)-based technologies closer to the clinic. This vision was achieved by assembling leaders in the field to cover critical areas. Some of these critical areas included regulatory pathways for regenerative medicine therapies, strategic partnerships, coordination of resources, developing standards for the field, government support, priorities for industry, biobanking, and new technologies. The final day of this conference featured focused sessions on manufacturing, during which expert speakers were invited from industry, government, and academia. The speakers identified and accessed roadblocks plaguing the field where improvements in advanced manufacturing offered many solutions. The manufacturing sessions included (a) product development toward commercialization in regenerative medicine, (b) process challenges to scale up manufacturing in regenerative medicine, and (c) infrastructure needs for manufacturing in regenerative medicine. Subsequent to this, industry was invited to participate in a survey to further elucidate the challenges to translation and scale-up. This perspective article will cover the lessons learned from these manufacturing sessions and early results from the survey. We also outline a road map for developing the manufacturing infrastructure, resources, standards, capabilities, education, training, and workforce development to realize the promise of TERM. PMID:25575525

  19. Manufacturing road map for tissue engineering and regenerative medicine technologies.

    PubMed

    Hunsberger, Joshua; Harrysson, Ola; Shirwaiker, Rohan; Starly, Binil; Wysk, Richard; Cohen, Paul; Allickson, Julie; Yoo, James; Atala, Anthony

    2015-02-01

    The Regenerative Medicine Foundation Annual Conference held on May 6 and 7, 2014, had a vision of assisting with translating tissue engineering and regenerative medicine (TERM)-based technologies closer to the clinic. This vision was achieved by assembling leaders in the field to cover critical areas. Some of these critical areas included regulatory pathways for regenerative medicine therapies, strategic partnerships, coordination of resources, developing standards for the field, government support, priorities for industry, biobanking, and new technologies. The final day of this conference featured focused sessions on manufacturing, during which expert speakers were invited from industry, government, and academia. The speakers identified and accessed roadblocks plaguing the field where improvements in advanced manufacturing offered many solutions. The manufacturing sessions included (a) product development toward commercialization in regenerative medicine, (b) process challenges to scale up manufacturing in regenerative medicine, and (c) infrastructure needs for manufacturing in regenerative medicine. Subsequent to this, industry was invited to participate in a survey to further elucidate the challenges to translation and scale-up. This perspective article will cover the lessons learned from these manufacturing sessions and early results from the survey. We also outline a road map for developing the manufacturing infrastructure, resources, standards, capabilities, education, training, and workforce development to realize the promise of TERM. ©AlphaMed Press.

  20. Controlling life: from Jacques Loeb to regenerative medicine.

    PubMed

    Maienschein, Jane

    2009-01-01

    In his 1987 book Controlling Life: Jacques Loeb and the Engineering Ideal in Biology, Philip Pauly presented his readers with the biologist Jacques Loeb and his role in developing an emphasis on control of life processes. Loeb's work on artificial parthenogenesis, for example, provided an example of bioengineering at work. This paper revisits Pauly's study of Loeb and explores the way current research in regenerative medicine reflects the same tradition. A history of regeneration research reveals patterns of thinking and research methods that both echo Loeb's ideology and point the way to modern studies. Pauly's work revealed far more than we readers realized at the time of its publication.

  1. Plastic Surgery Challenges in War Wounded II: Regenerative Medicine

    PubMed Central

    Valerio, Ian L.; Sabino, Jennifer M.; Dearth, Christopher L.

    2016-01-01

    Background: A large volume of service members have sustained complex injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). These injuries are complicated by contamination with particulate and foreign materials, have high rates of bacterial and/or fungal infections, are often composite-type defects with massive soft tissue wounds, and usually have multisystem involvement. While traditional treatment modalities remain a mainstay for optimal wound care, traditional reconstruction approaches alone may be inadequate to fully address the scope and magnitude of such massive complex wounds. As a result of these difficult clinical problems, the use of regenerative medicine therapies, such as autologous adipose tissue grafting, stem cell therapies, nerve allografts, and dermal regenerate templates/extracellular matrix scaffolds, is increased as adjuncts to traditional reconstructive measures. Basic and Clinical Science Advances: The beneficial applications of regenerative medicine therapies have been well characterized in both in vitro studies and in vivo animal studies. The use of these regenerative medicine techniques in the treatment of combat casualty injuries has been increasing throughout the recent war conflicts. Clinical Care Relevance: Military medicine has shown positive results when utilizing certain regenerative medicine modalities in treating complex war wounds. As a result, multi-institution clinical trials are underway to further evaluate these observations and reconstruction measures. Conclusion: Successful combat casualty wound care often requires a combination of traditional aspects of the reconstructive ladder/elevator with adoption of various regenerative medicine therapies. Due to the recent OIF/OEF conflicts, a high volume of combat casualties have benefited from adoption of regenerative medicine therapies and increased access to innovative clinical trials. Furthermore, many of these patients have had long-term follow-up to report

  2. Plastic Surgery Challenges in War Wounded II: Regenerative Medicine.

    PubMed

    Valerio, Ian L; Sabino, Jennifer M; Dearth, Christopher L

    2016-09-01

    Background: A large volume of service members have sustained complex injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). These injuries are complicated by contamination with particulate and foreign materials, have high rates of bacterial and/or fungal infections, are often composite-type defects with massive soft tissue wounds, and usually have multisystem involvement. While traditional treatment modalities remain a mainstay for optimal wound care, traditional reconstruction approaches alone may be inadequate to fully address the scope and magnitude of such massive complex wounds. As a result of these difficult clinical problems, the use of regenerative medicine therapies, such as autologous adipose tissue grafting, stem cell therapies, nerve allografts, and dermal regenerate templates/extracellular matrix scaffolds, is increased as adjuncts to traditional reconstructive measures. Basic and Clinical Science Advances: The beneficial applications of regenerative medicine therapies have been well characterized in both in vitro studies and in vivo animal studies. The use of these regenerative medicine techniques in the treatment of combat casualty injuries has been increasing throughout the recent war conflicts. Clinical Care Relevance: Military medicine has shown positive results when utilizing certain regenerative medicine modalities in treating complex war wounds. As a result, multi-institution clinical trials are underway to further evaluate these observations and reconstruction measures. Conclusion: Successful combat casualty wound care often requires a combination of traditional aspects of the reconstructive ladder/elevator with adoption of various regenerative medicine therapies. Due to the recent OIF/OEF conflicts, a high volume of combat casualties have benefited from adoption of regenerative medicine therapies and increased access to innovative clinical trials. Furthermore, many of these patients have had long-term follow-up to report

  3. The continued promise of stem cell therapy in regenerative medicine.

    PubMed

    Eve, David J

    2011-12-01

    The use of stem cells is galvanizing regenerative medicine research. An analysis of recent trends as typified by articles published between 2009 and 2010 in the journals Cell Transplantation--The Regenerative Medicine Journal and Medical Science Monitor demonstrate the increasing importance of stem cell research as being on the cutting edge of regenerative medicine research. The analysis revealed an even split between transplantation and non-transplantation studies, showing that both the applicability and general research is being pursued. New methods and tissue engineering are also highly important components of regenerative medicine as demonstrated by a number of the stem cell studies being involved with either ex vivo manipulation, or cotransplantation with other cells or biomaterials. This suggests that the best results may be achieved with adjuvant therapies. The non-transplantation studies were more focused on manipulation of transplantable agents including cells and scaffold systems, as well as the use of medicines and dietary supplements. The further elucidation of disease mechanisms was a major contribution. This analysis suggests that regenerative medicine is proceeding at a rapid pace and the next few years should be of considerable interest with the initial results of pioneering stem cell therapies being announced.

  4. Genetically modified cells in regenerative medicine and tissue engineering.

    PubMed

    Sheyn, Dima; Mizrahi, Olga; Benjamin, Shimon; Gazit, Zulma; Pelled, Gadi; Gazit, Dan

    2010-06-15

    Regenerative medicine appears to take as its patron, the Titan Prometheus, whose liver was able to regenerate daily, as the field attempts to restore lost, damaged, or aging cells and tissues. The tremendous technological progress achieved during the last decade in gene transfer methods and imaging techniques, as well as recent increases in our knowledge of cell biology, have opened new horizons in the field of regenerative medicine. Genetically engineered cells are a tool for tissue engineering and regenerative medicine, albeit a tool whose development is fraught with difficulties. Gene-and-cell therapy offers solutions to severe problems faced by modern medicine, but several impediments obstruct the path of such treatments as they move from the laboratory toward the clinical setting. In this review we provide an overview of recent advances in the gene-and-cell therapy approach and discuss the main hurdles and bottlenecks of this approach on its path to clinical trials and prospective clinical practice.

  5. Promissory identities: Sociotechnical representations & innovation in regenerative medicine.

    PubMed

    Gardner, John; Higham, Ruchi; Faulkner, Alex; Webster, Andrew

    2017-02-01

    The field of regenerative medicine (RM) is championed as a potential source of curative treatments and economic wealth, and initiatives have been launched in several countries to facilitate innovation within the field. As a way of examining the social dimensions of innovation within regenerative medicine, this paper explores the sociotechnical representations of RM technologies in the UK, and the tensions, affordances and complexities these representations present for actors within the field. Specifically, the paper uses the Science and Technology Studies-inspired notions of 'technology identity' and 'development space' to examine how particular technologies are framed and positioned by actors, and how these positionings subsequently shape innovation pathways. Four developing RM technologies are used as case studies: bioengineered tracheas; autologous chondrocyte implantation; T-cell therapies; and a 'point-of-care' cell preparation device. Using these case studies we argue that there are particular identity aspects that have powerful performative effects and provide momentum to innovation projects, and we argue that there are particular stakeholders in the UK RM landscape who appear to have considerable power in shaping these technology identities and thus innovation pathways.

  6. Induced pluripotent stem cells and their implication for regenerative medicine.

    PubMed

    Csobonyeiova, Maria; Polak, Stefan; Koller, Jan; Danisovic, Lubos

    2015-06-01

    In 2006 Yamanaka's group showed that stem cells with properties similar to embryonic stem cells could be generated from mouse fibroblasts by introducing four genes. These cells were termed induced pluripotent stem cells (iPSCs). Because iPSCs avoid many of ethical concerns associated with the use of embryonic material, they have great potential in cell-based regenerative medicine. They are suitable also for other various purposes, including disease modelling, personalized cell therapy, drug or toxicity screening and basic research. Moreover, in the future, there might become possible to generate organs for human transplantation. Despite these progresses, several studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to immunogenicity of some cells differentiated from iPSCs. Recent methodological improvements are increasing the ease and efficacy of reprogramming, and reducing the genomic modification. However, to minimize or eliminate genetic alternations in the derived iPSC line creation, factor-free human iPSCs are necessary. In this review we discuss recent possibilities of using iPSCs for clinical applications and new advances in field of their reprogramming methods. The main goal of present article was to review the current knowledge about iPSCs and to discuss their potential for regenerative medicine.

  7. Amniotic fluid-derived stem cells in regenerative medicine research.

    PubMed

    Joo, Sunyoung; Ko, In Kap; Atala, Anthony; Yoo, James J; Lee, Sang Jin

    2012-02-01

    The stem cells isolated from amniotic fluid present an exciting possible contribution to the field of regenerative medicine and amniotic fluid-derived stem (AFS) cells have significant potential for research and therapeutic applications. AFS cells are multipotent, showing the ability to differentiate into cell types from all three embryonic germ layers. They express both embryonic and adult stem cell markers, expand extensively without feeder cells, double in 36 h, and are not tumorigenic. The AFS cells can be maintained for over 250 population doublings and preserve their telomere length and a normal karyotype. They differentiate easily into specific cell lineages and do not require human embryo tissue for their isolation, thus avoiding the current controversies associated with the use of human embryonic stem (ES) cells. The discovery of the AFS cells has been recent, and a great deal of work remains to be performed on the characterization and use of these cells. This review describes the various differentiated lineages that AFS cells can form and the future of these promising new stem cells in regenerative medicine research.

  8. Diverging Concepts and Novel Perspectives in Regenerative Medicine

    PubMed Central

    Muraca, Maurizio; Piccoli, Martina; Franzin, Chiara; Tolomeo, Anna Maria; Jurga, Marcin; Pozzobon, Michela; Perilongo, Giorgio

    2017-01-01

    Regenerative medicine has rapidly evolved, due to progress in cell and molecular biology allowing the isolation, characterization, expansion, and engineering of cells as therapeutic tools. Despite past limited success in the clinical translation of several promising preclinical results, this novel field is now entering a phase of renewed confidence and productivity, marked by the commercialization of the first cell therapy products. Ongoing issues in the field include the use of pluripotent vs. somatic and of allogenic vs. autologous stem cells. Moreover, the recognition that several of the observed beneficial effects of cell therapy are not due to integration of the transplanted cells, but rather to paracrine signals released by the exogenous cells, is generating new therapeutic perspectives in the field. Somatic stem cells are outperforming embryonic and induced pluripotent stem cells in clinical applications, mainly because of their more favorable safety profile. Presently, both autologous and allogeneic somatic stem cells seem to be equally safe and effective under several different conditions. Recognition that a number of therapeutic effects of transplanted cells are mediated by paracrine signals, and that such signals can be found in extracellular vesicles isolated from culture media, opens novel therapeutic perspectives in the field of regenerative medicine. PMID:28486410

  9. Regenerative Medicine for Periodontal and Peri-implant Diseases.

    PubMed

    Larsson, L; Decker, A M; Nibali, L; Pilipchuk, S P; Berglundh, T; Giannobile, W V

    2016-03-01

    The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions.

  10. Regenerative Medicine for Periodontal and Peri-implant Diseases

    PubMed Central

    Larsson, L.; Decker, A.M.; Nibali, L.; Pilipchuk, S.P.; Berglundh, T.; Giannobile, W.V.

    2015-01-01

    The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions. PMID:26608580

  11. Particle assemblies: toward new tools for regenerative medicine.

    PubMed

    Roux, R; Ladavière, C; Montembault, A; Delair, T

    2013-04-01

    Regenerative medicine is a demanding field in terms of design and elaboration of materials able to meet the specifications that this application imposes. The regeneration of tissue is a multiscale issue, from the signaling molecule through cell expansion and finally tissue growth requiring a large variety of cues that should be delivered in place and time. Hence, the materials should be able to accommodate cells with respect to their phenotypes, to allow cell division to the right tissue, to maintain the integrity of the surrounding sane tissue, and eventually use their signaling machinery to serve the development of the appropriate neo-tissue. They should also present the ability to deliver growth factors and regulate tissue development, to be degraded into safe products, in order not to impede tissue development, and finally be easily implanted/injected into the patients. In this context, colloid-based materials represent a very promising family of products because one can take advantage of their high specific area, their capability to carry/deliver bio-active molecules, and their capacity of assembling (eventually in vivo) into materials featuring other mechanical, rheological, physicochemical properties. Other benefits of great interest would be their ease of production even via high through-put processes and their potential manufacturing from safe, biodegradable and biocompatible parent raw material. This review describes the state-of-the-art of processes leading to complex materials from the assembly of colloids meeting, at least partially, the above-described specifications for tissue engineering and regenerative medicine.

  12. Dedifferentiation, transdifferentiation, and reprogramming: future directions in regenerative medicine.

    PubMed

    Eguizabal, Cristina; Montserrat, Nuria; Veiga, Anna; Izpisua Belmonte, Juan Carlos

    2013-01-01

    The main goal of regenerative medicine is to replace damaged tissue. To do this it is necessary to understand in detail the whole regeneration process including differentiated cells that can be converted into progenitor cells (dedifferentiation), cells that can switch into another cell type (transdifferentiation), and somatic cells that can be induced to become pluripotent cells (reprogramming). By studying the regenerative processes in both nonmammal and mammal models, natural or artificial processes could underscore the molecular and cellular mechanisms behind these phenomena and be used to create future regenerative strategies for humans.

  13. Stem cells have the potential to rejuvenate regenerative medicine research.

    PubMed

    Eve, David J; Fillmore, Randolph; Borlongan, Cesar V; Sanberg, Paul R

    2010-10-01

    The increasing number of publications featuring the use of stem cells in regenerative processes supports the idea that they are revolutionizing regenerative medicine research. In an analysis of the articles published in the journal Cell Transplantation - The Regenerative Medicine Journal between 2008 and 2009, which reveals the topics and categories that are on the cutting edge of regenerative medicine research, stem cells are becoming increasingly relevant as the "runner-up" category to "neuroscience" related articles. The high volume of stem cell research casts a bright light on the hope for stem cells and their role in regenerative medicine as a number of reports deal with research using stem cells entering, or seeking approval for, clinical trials. The "methods and new technologies" and "tissue engineering" sections were almost equally as popular, and in part, reflect attempts to maximize the potential of stem cells and other treatments for the repair of damaged tissue. Transplantation studies were again more popular than non-transplantation, and the contribution of stem cell-related transplants was greater than other types of transplants. The non-transplantation articles were predominantly related to new methods for the preparation, isolation and manipulation of materials for transplant by specific culture media, gene therapy, medicines, dietary supplements, and co-culturing with other cells and further elucidation of disease mechanisms. A sizeable proportion of the transplantation articles reported on how previously new methods may have aided the ability of the cells or tissue to exert beneficial effects following transplantation.

  14. Immunosuppression-free transplantation reconsidered from a regenerative medicine perspective.

    PubMed

    Orlando, Giuseppe

    2012-02-01

    Recent groundbreaking progress in regenerative medicine has shown its potential to meet the two major needs of solid organ transplantation, namely the achievement of an immunosuppression-free state (IFS) and the identification of a new, potentially inexhaustible source of organs. This review illustrates how regenerative medicine technology may contribute to the achievement of IFS. There are three possible strategies: organ bioengineering, immuno-isolation and thymus bioengineering. The goal of organ bioengineering is to manufacture organs ex vivo from autologous cells. Immuno-isolation technology implements strategies aiming to prevent recognition of nonself antigens by the host immune system. Thymus organoids have been bioengineered with scaffold-seeding methods to allow deletion of T-cell clones responsible for allograft rejection. Despite the several hurdles that must be overcome, regenerative medicine technologies offer alternative strategies aimed at establishing immediate, stable and durable IFS in solid organ graft recipients.

  15. Proteins and Small Molecules for Cellular Regenerative Medicine

    PubMed Central

    Green, Eric M.

    2013-01-01

    Regenerative medicine seeks to understand tissue development and homeostasis and build on that knowledge to enhance regeneration of injured tissues. By replenishing lost functional tissues and cells, regenerative medicine could change the treatment paradigm for a broad range of degenerative and ischemic diseases. Multipotent cells hold promise as potential building blocks for regenerating lost tissues, but successful tissue regeneration will depend on comprehensive control of multipotent cells–differentiation into a target cell type, delivery to a desired tissue, and integration into a durable functional structure. At each step of this process, proteins and small molecules provide essential signals and, in some cases, may themselves act as effective therapies. Identifying these signals is thus a fundamental goal of regenerative medicine. In this review we discuss current progress using proteins and small molecules to regulate tissue regeneration, both in combination with cellular therapies and as monotherapy. PMID:23303911

  16. Gene delivery in tissue engineering and regenerative medicine.

    PubMed

    Fang, Y L; Chen, X G; W T, Godbey

    2015-11-01

    As a promising strategy to aid or replace tissue/organ transplantation, gene delivery has been used for regenerative medicine applications to create or restore normal function at the cell and tissue levels. Gene delivery has been successfully performed ex vivo and in vivo in these applications. Excellent proliferation capabilities and differentiation potentials render certain cells as excellent candidates for ex vivo gene delivery for regenerative medicine applications, which is why multipotent and pluripotent cells have been intensely studied in this vein. In this review, gene delivery is discussed in detail, along with its applications to tissue engineering and regenerative medicine. A definition of a stem cell is compared to a definition of a stem property, and both provide the foundation for an in-depth look at gene delivery investigations from a germ lineage angle.

  17. Nanotechnology-based approaches for regenerative medicine and biosensing

    NASA Astrophysics Data System (ADS)

    Solanki, Aniruddh P.

    The recent emergence of nanotechnology has set high expectations in many fields of science, especially in biology and medicine. Nanotechnology-based approaches are expected to solve key questions in the emerging field of regenerative medicine. Regenerative medicine essentially deals with regeneration of cells, ultimately leading to the formation of tissues and organs. For this purpose, stem cells, embryonic stem cells or adult stem cells, are thought to be ideal resources. However, many challenges need to be addressed before the full therapeutic potential of stem cells can be harnessed. Controlling the differentiation of stem cells into cells of a specific lineage is extremely vital and challenging. Addressing this challenge, in this work, novel nanotechnology-based approaches for controlling the differentiation of neural stem cells (NSCs) into neurons has been presented. Regeneration of damaged neurons, due to traumatic injuries or degenerative diseases, is extremely challenging. For this purpose, NSCs can be used as resources that can differentiate into neurons, thus having great potential in solving needs of many patients suffering from such conditions. For controlling the differentiation of stem cells, soluble cues (comprising of small molecules and biomolecules) and insoluble cues (cell-cell interactions and cell-microenvironment interactions) play a very important role. The delivery of soluble cues, such as genetic material, into stem cells is extremely challenging. The initial part of this work presents the use of nanomaterials for efficiently delivering soluble cues such as small molecules and small interfering RNA (siRNA) into NSCs for controlling their differentiation into neurons. However, for regenerative purposes, it is preferred that least amounts of the delivery vehicle be used. Thus, the following part of the thesis presents the development and applications of nanotechnology-based approaches for enhancing the differentiation of NSCs into neurons

  18. Reprogramming and transdifferentiation shift the landscape of regenerative medicine.

    PubMed

    Guo, Jingjing; Wang, Hu; Hu, Xingchang

    2013-10-01

    Regenerative medicine is a new interdisciplinary field in biomedical science, which aims at the repair or replacement of the defective tissue or organ by congenital defects, age, injury, or disease. Various cell-related techniques such as stem cell-based biotherapy are a hot topic in the current press, and stem cell research can help us to expand our understanding of development as well as the pathogenesis of disease. In addition, new technology such as reprogramming or dedifferentiation and transdifferentiation open a new area for regenerative medicine. Here we review new approaches of these technologies used for cell-based therapy and discuss future directions and challenges in the field of regeneration.

  19. Regenerative Medicine: Charting a New Course in Wound Healing

    PubMed Central

    Gurtner, Geoffrey C.; Chapman, Mary Ann

    2016-01-01

    Significance: Chronic wounds are a prevalent and costly problem in the United States. Improved treatments are needed to heal these wounds and prevent serious complications such as infection and amputation. Recent Advances: In wound healing, as in other areas of medicine, technologies that have the potential to regenerate as opposed to repair tissue are gaining ground. These include customizable nanofiber matrices incorporating novel materials; a variety of autologous and allogeneic cell types at various stages of differentiation (e.g., pluripotent, terminally differentiated); peptides; proteins; small molecules; RNA inhibitors; and gene therapies. Critical Issues: Wound healing is a logical target for regenerative medicine due to the accessibility and structure of skin, the regenerative nature of healing, the lack of good limb salvage treatments, and the current use of cell therapies. However, more extensive knowledge of pathophysiologic targets is needed to inform regenerative strategies, and new technologies must demonstrate value in terms of outcomes and related health economic measures to achieve successful market access and penetration. Future Directions: Due to similarities in cell pathways and developmental mechanisms, regenerative technologies developed in one therapeutic area may be applicable to others. Approaches that proceed from human genomic or other big data sources to models are becoming increasingly common and will likely suggest novel therapeutic avenues. To fully capitalize on the advances in regenerative medicine, studies must demonstrate the value of new therapies in identified patient populations, and sponsors must work with regulatory agencies to develop appropriate dossiers supporting timely approval. PMID:27366592

  20. Turning Regenerative Medicine Breakthrough Ideas and Innovations into Commercial Products.

    PubMed

    Bayon, Yves; Vertès, Alain A; Ronfard, Vincent; Culme-Seymour, Emily; Mason, Chris; Stroemer, Paul; Najimi, Mustapha; Sokal, Etienne; Wilson, Clayton; Barone, Joe; Aras, Rahul; Chiesi, Andrea

    2015-12-01

    The TERMIS-Europe (EU) Industry committee intended to address the two main critical issues in the clinical/commercial translation of Advanced Therapeutic Medicine Products (ATMP): (1) entrepreneurial exploitation of breakthrough ideas and innovations, and (2) regulatory market approval. Since January 2012, more than 12,000 publications related to regenerative medicine and tissue engineering have been accepted for publications, reflecting the intense academic research activity in this field. The TERMIS-EU 2014 Industry Symposium provided a reflection on the management of innovation and technological breakthroughs in biotechnology first proposed to contextualize the key development milestones and constraints of allocation of financial resources, in the development life-cycle of radical innovation projects. This was illustrated with the biofuels story, sharing similarities with regenerative medicine. The transition was then ensured by an overview of the key identified challenges facing the commercialization of cell therapy products as ATMP examples. Real cases and testimonies were then provided by a palette of medical technologies and regenerative medicine companies from their commercial development of cell and gene therapy products. Although the commercial development of ATMP is still at the proof-of-concept stage due to technology risks, changing policies, changing markets, and management changes, the sector is highly dynamic with a number of explored therapeutic approaches, developed by using a large diversity of business models, both proposed by the experience, pitfalls, and successes of regenerative medicine pioneers, and adapted to the constraint resource allocation and environment in radical innovation projects.

  1. Stem cells and regenerative medicine in domestic and companion animals: a multispecies perspective.

    PubMed

    Gonçalves, N N; Ambrósio, C E; Piedrahita, J A

    2014-10-01

    Since their original isolation, the majority of the work on embryonic stem cells (ESC) has been carried out in mice. While the mouse is an outstanding model for basic research, it also has considerable limitations for translational work, especially in the area of regenerative medicine. This is due to a combination of factors that include physiological and size differences when compared to humans. In contrast, domestic animal species, such as swine, and companion animal species, such as dogs, provide unique opportunities to develop regenerative medicine protocols that can then be utilized in humans. Unfortunately, at present, the state of knowledge related to, and availability of, ESC from domestic animals vary among species such as pig, horse, dog and cat, and without exception lags significantly behind the mouse and human. It is clear that much still needs to be discovered. The 'stem cell-like' cell lines being reported are still not satisfactorily used in regenerative medicine, due to reasons such as heterogeneity and chromosomal instability. As a result, investigators have searched for alternate source of cells that can be used for regenerative medicine. This approach has uncovered a range of adult stem cells and adult progenitor cells that have utility in both human and veterinary medicine. Here, we review a range of stem cells, from ESC to induced pluripotent stem cells, and discuss their potential application in the field of regenerative medicine.

  2. Extracellular Matrix Scaffolds for Tissue Engineering and Regenerative Medicine.

    PubMed

    Yi, Sheng; Ding, Fei; Gong, Leiiei; Gu, Xiaosong

    2017-01-01

    The extracellular matrix is produced by the resident cells in tissues and organs, and secreted into the surrounding medium to provide biophysical and biochemical support to the surrounding cells due to its content of diverse bioactive molecules. Recently, the extracellular matrix has been used as a promising approach for tissue engineering. Emerging studies demonstrate that extracellular matrix scaffolds are able to create a favorable regenerative microenvironment, promote tissue-specific remodeling, and act as an inductive template for the repair and functional reconstruction of skin, bone, nerve, heart, lung, liver, kidney, small intestine, and other organs. In the current review, we will provide a critical overview of the structure and function of various types of extracellular matrix, the construction of three-dimensional extracellular matrix scaffolds, and their tissue engineering applications, with a focus on translation of these novel tissue engineered products to the clinic. We will also present an outlook on future perspectives of the extracellular matrix in tissue engineering and regenerative medicine.

  3. Anti-HLA antibodies in regenerative medicine stem cell therapy.

    PubMed

    Charron, Dominique; Suberbielle-Boissel, Caroline; Tamouza, Ryad; Al-Daccak, Reem

    2012-12-01

    Research on stem cell therapies for regenerative medicine is progressing rapidly. Although the use of autologous stem cells is a tempting choice, there are several instances in which they are either defective or not available in due time. Allogenic stem cells derived from healthy donors presents a promising alternative. Whether autologous or allogenic, recent advances have proven that stem cells are not as immune privileged as they were thought. Therefore understanding the interactions of these cells with the recipient immune system is paramount to their clinical application. Transplantation of stem cells induces humoral as well as cellular immune response. This review focuses on the humoral response elicited by stem cells upon their administration and consequences on the survival and maintenance of the graft. Current transplantation identifies pre- and post-transplantation anti-HLA antibodies as immune rejection and cell signaling effectors. These two mechanisms are likely to operate similarly in the context of SC therapeutics. Ultimately this knowledge will help to propose novel strategies to mitigate the allogenic barriers. Immunogenetics selection of the donor cell and immunomonitoring are key factors to allow the implementation of regenerative stem cell in the clinics. Copyright © 2012. Published by Elsevier Inc.

  4. The strong financial case for regenerative medicine and the regen industry.

    PubMed

    Mason, Chris; Dunnill, Peter

    2008-05-01

    Although the therapeutic promise of regenerative medicine is immensely exciting, the cost of product development, and particularly of clinical trials, for the more demanding applications will be high. For this reason it is vital for scientists and start-ups who wish to see their ideas implemented to be able to convince established major pharmaceutical or device companies with the necessary 'deep pockets' that the expenditure can yield an appropriate return. It also means that governments and health insurance companies must see a gain in funding regenerative medicine for patients. To address this issue the costs of five major medical conditions that could benefit from regenerative medicine have been defined for the USA as an illustration. This choice of country was made as potentially the largest initial market and one where the billing system for healthcare allows access to individual direct and some indirect costs. The data are complemented by a number of relevant examples of costs per quality-adjusted life year to indicate where current treatment methods are weak or strong. Finally, the relationship of the nascent regen* industry to the pharma and medical device sectors is summarized to assess the challenge of encouraging their involvement.

  5. 25th Anniversary Article: Supramolecular Materials for Regenerative Medicine

    PubMed Central

    Boekhoven, Job

    2014-01-01

    In supramolecular materials, molecular building blocks are designed to interact with one another via non-covalent interactions in order to create function. This offers the opportunity to create structures similar to those found in living systems that combine order and dynamics through the reversibility of intermolecular bonds. For regenerative medicine there is a great need to develop materials that signal cells effectively, deliver or bind bioactive agents in vivo at controlled rates, have highly tunable mechanical properties, but at the same time, can biodegrade safely and rapidly after fulfilling their function. These requirements make supramolecular materials a great platform to develop regenerative therapies. This review illustrates the emerging science of these materials and their use in a number of applications for regenerative medicine. PMID:24496667

  6. Cell sheet approach for tissue engineering and regenerative medicine.

    PubMed

    Matsuura, Katsuhisa; Utoh, Rie; Nagase, Kenichi; Okano, Teruo

    2014-09-28

    After the biotech medicine era, regenerative medicine is expected to be an advanced medicine that is capable of curing patients with difficult-to-treat diseases and physically impaired function. Our original scaffold-free cell sheet-based tissue engineering technology enables transplanted cells to be engrafted for a long time, while fully maintaining their viability. This technology has already been applied to various diseases in the clinical setting, including the cornea, esophagus, heart, periodontal ligament, and cartilage using autologous cells. Transplanted cell sheets not only replace the injured tissue and compensate for impaired function, but also deliver growth factors and cytokines in a spatiotemporal manner over a prolonged period, which leads to promotion of tissue repair. Moreover, the integration of stem cell biology and cell sheet technology with sufficient vascularization opens possibilities for fabrication of human three-dimensional vascularized dense and intact tissue grafts for regenerative medicine to parenchymal organs.

  7. Nanotechnologies and regenerative medical approaches for space and terrestrial medicine.

    PubMed

    Grattoni, Alessandro; Tasciotti, Ennio; Fine, Daniel; Fernandez-Moure, Joseph S; Sakamoto, Jason; Hu, Ye; Weiner, Bradley; Ferrari, Mauro; Parazynski, Scott

    2012-11-01

    One purpose of the International Space Station (ISS) is to explore powerful new areas of biomedical science in microgravity. Recent advances in nanotechnology applied to medicine--what we now refer to as nano-medicine--and regenerative medicine have enormous untapped potential for future space and terrestrial medical applications. Novel means for drug delivery and nanoscale screening tools will one day benefit astronauts venturing to Mars and places beyond, while the space laboratory will foster advances in nanotechnologies for diagnostic and therapeutic tools to help our patients here on Earth. Herein we review a series of nanotechnologies and selected regenerative medical approaches and highlight key areas of ongoing and future investigation that will benefit both space and terrestrial medicine. These studies target significant areas of human disease such as osteoporosis, diabetes, radiation injury, and many others.

  8. Trends in biomedical engineering: focus on Regenerative Medicine.

    PubMed

    Asnaghi, M Adelaide; Candiani, Gabriele; Farè, Silvia; Fiore, Gianfranco B; Petrini, Paola; Raimondi, Manuela T; Soncini, Monica; Mantero, Sara

    2011-01-01

    Regenerative medicine is a critical frontier in biomedical and clinical research. The major progresses in the last few years were driven by a strong clinical need which could benefit from regenerative medicine outcomes for the treatment of a large number of conditions including birth defects, degenerative and neoplastic diseases, and traumatic injuries. Regenerative medicine applies the principles of engineering and life sciences to enhance the comprehension of the fundamental biological mechanisms underlying the structure-function relationships in physiologic and pathologic tissues and to accomplish alternative strategies for developing in vitro biological substitutes which are able to restore, maintain, or improve tissue, and organ function. This paper reviews selected approaches currently being investigated at Politecnico di Milano in the field of regenerative medicine. Specific tissue-oriented topics are divided in three sections according to each developmental stage: in vitro study, pre-clinical study, and clinical application. In vitro studies investigate the basic phenomena related to gene delivery, stem cell behavior, tissue regeneration, and to explore dynamic culture potentiality in different applications: cardiac and skeletal muscle, cartilage, hematopoietic system, peripheral nerve, and gene delivery. Specific fields of regenerative medicine, i.e., bone, blood vessels, and ligaments engineering have already reached the preclinical stage providing promising insights for further research towards clinical applications. The translation of the results obtained during in vitro and preclinical steps into clinical organ replacement is a very challenging issue, which can offer a valid alternative to fight morbidity, organ shortage, and ethical-social problems associated with allotransplantation as shown in the clinical case reported in this review.

  9. The current 'state of play' of regenerative medicine in horses: what the horse can tell the human.

    PubMed

    Smith, Roger Kw; Garvican, Elaine R; Fortier, Lisa A

    2014-01-01

    The horse is an attractive model for many human age-related degenerative diseases of the musculoskeletal system because it is a large animal species that both ages and exercises, and develops naturally occurring injuries with many similarities to the human counterpart. It therefore represents an ideal species to use as a 'proving ground' for new therapies, most notably regenerative medicine. Regenerative techniques using cell-based therapies for the treatment of equine musculoskeletal disease have been in use for over a decade. This review article provides a summary overview of the sources, current challenges and problems surrounding the use of stem cell and non-cell-based therapy in regenerative medicine in horses and is based on presentations from a recent Havemeyer symposium on equine regenerative medicine where speakers are selected from leading authorities in both equine and human regenerative medicine fields from 10 different countries.

  10. Stem cell bioprinting for applications in regenerative medicine.

    PubMed

    Tricomi, Brad J; Dias, Andrew D; Corr, David T

    2016-11-01

    Many regenerative medicine applications seek to harness the biologic power of stem cells in architecturally complex scaffolds or microenvironments. Traditional tissue engineering methods cannot create such intricate structures, nor can they precisely control cellular position or spatial distribution. These limitations have spurred advances in the field of bioprinting, aimed to satisfy these structural and compositional demands. Bioprinting can be defined as the programmed deposition of cells or other biologics, often with accompanying biomaterials. In this concise review, we focus on recent advances in stem cell bioprinting, including performance, utility, and applications in regenerative medicine. More specifically, this review explores the capability of bioprinting to direct stem cell fate, engineer tissue(s), and create functional vascular networks. Furthermore, the unique challenges and concerns related to bioprinting living stem cells, such as viability and maintaining multi- or pluripotency, are discussed. The regenerative capacity of stem cells, when combined with the structural/compositional control afforded by bioprinting, provides a unique and powerful tool to address the complex demands of tissue engineering and regenerative medicine applications.

  11. Stem cells: a promising source for vascular regenerative medicine.

    PubMed

    Rammal, Hassan; Harmouch, Chaza; Lataillade, Jean-Jacques; Laurent-Maquin, Dominique; Labrude, Pierre; Menu, Patrick; Kerdjoudj, Halima

    2014-12-15

    The rising and diversity of many human vascular diseases pose urgent needs for the development of novel therapeutics. Stem cell therapy represents a challenge in the medicine of the twenty-first century, an area where tissue engineering and regenerative medicine gather to provide promising treatments for a wide variety of diseases. Indeed, with their extensive regeneration potential and functional multilineage differentiation capacity, stem cells are now highlighted as promising cell sources for regenerative medicine. Their multilineage differentiation involves environmental factors such as biochemical, extracellular matrix coating, oxygen tension, and mechanical forces. In this review, we will focus on human stem cell sources and their applications in vascular regeneration. We will also discuss the different strategies used for their differentiation into both mature and functional smooth muscle and endothelial cells.

  12. Regenerative Medicinal Chemistry: The in Situ Control of Stem Cells

    PubMed Central

    2013-01-01

    In recent years, there has been mounting evidence to support the presence of stem and progenitor cells within many adult tissues that retain the capacity to proliferate and differentiate, thereby contributing to tissue homeostasis and repair. In line with these discoveries, there have been increasing efforts to develop new agents that target these resident stem and progenitor cell populations in situ to augment or to stimulate repair and regeneration processes. Two such agents are approved drugs, and several more are currently in clinical and preclinical development. Through this emerging therapeutic paradigm there is enormous scope for medicinal chemistry to play a pivotal role in regenerative medicine. The potential impact of regenerative medicinal chemistry is profound, and future studies will reveal which tissue types or disease states will prove most readily tractable through this approach. PMID:24900675

  13. PLURIPOTENT STEM CELL APPLICATIONS FOR REGENERATIVE MEDICINE

    PubMed Central

    Angelos, Mathew G.; Kaufman, Dan S.

    2015-01-01

    Purpose of Review In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We also discuss combined cell and gene therapy via correction of defined mutations in human pluripotent stem cells and provide commentary on key obstacles facing wide-scale clinical adoption of pluripotent stem cell-based therapy. Recent Findings Initial data suggest hESC/hiPSC-derived cell products used for retinal repair and spinal cord injury are safe for human use. Early stage studies for treatment of cardiac injury and diabetes are also in progress. However, there remain key concerns regarding the safety and efficacy of these cells that need to be addressed in additional well-designed clinical trials. Advances using the CRISPR/Cas9 gene-editing system offer an improved tool for more rapid and on-target gene correction of genetic diseases. Combined gene and cell therapy using human pluripotent stem cells may provide an additional curative approach for disabling or lethal genetic and degenerative diseases where there are currently limited therapeutic opportunities. Summary Human pluripotent stem cells are emerging as a promising tool to produce cells and tissues suitable for regenerative therapy for a variety of genetic and degenerative diseases. PMID:26536430

  14. Systemically Administered, Target Organ-Specific Therapies for Regenerative Medicine

    PubMed Central

    Järvinen, Tero A. H.; May, Ulrike; Prince, Stuart

    2015-01-01

    Growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic value in clinical medicine has been limited for reasons such as difficulty to maintain bioactivity of locally applied therapeutics in the protease-rich environment of regenerating tissues. Although human diseases are treated with systemically administered drugs in general, all current efforts aimed at enhancing tissue repair with biological drugs have been based on their local application. The systemic administration of growth factors has been ruled out due to concerns about their safety. These concerns are warranted. In addition, only a small proportion of systemically administered drugs reach their intended target. Selective delivery of the drug to the target tissue and use of functional protein domains capable of penetrating cells and tissues could alleviate these problems in certain circumstances. We will present in this review a novel approach utilizing unique molecular fingerprints (“Zip/postal codes”) in the vasculature of regenerating tissues that allows target organ-specific delivery of systemically administered therapeutic molecules by affinity-based physical targeting (using peptides or antibodies as an “address tag”) to injured tissues undergoing repair. The desired outcome of targeted therapies is increased local accumulation and lower systemic concentration of the therapeutic payload. We believe that the physical targeting of systemically administered therapeutic molecules could be rapidly adapted in the field of regenerative medicine. PMID:26437400

  15. Commercialization of regenerative medicine: learning from spin-outs.

    PubMed

    French, Anna; Buckler, R Lee; Brindley, David A

    2013-04-01

    Abstract The meeting "Commercialization of Your Regenerative Medicine Research: Lessons from Spin Out Successes" was hosted by the Oxbridge Biotech Roundtable (OBR) (Oxford, UK) at the University of Oxford in February, 2013, and attracted a multi-stakeholder audience spanning academia and industry. The event featured case studies from Gregg Sando, CEO, Cell Medica (London, UK), John Sinden, CSO, Reneuron (Guilford, UK), and Paul Kemp, CEO and CSO, Intercytex (Manchester, UK). OBR is a student-led initiative with over 7000 members across eight different UK and US locations with a mission to foster a conversation about the healthcare and life sciences industry. Here we review the main themes of the meeting and the major questions facing the regenerative medicine industry and its rapidly emerging subsets of cellular and gene therapies. Notably, we discuss the compatibility of regenerative therapies to the existing healthcare infrastructure, biomanufacturing challenges (including scalability and comparability), and the amenability of regenerative therapies to existing reimbursement and investment models. Furthermore, we reiterate key words of advice from seasoned industry leaders intended to accelerate the translation path from lab bench to the marketplace.

  16. Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges

    PubMed Central

    Law, Sujata; Chaudhuri, Samaresh

    2013-01-01

    Mesenchymal Stem cells (MSC) are now presented with the opportunities of multifunctional therapeutic approaches. Several reports are in support of their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties. They are unique to contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. In addition to promising trials in regenerative medicine, such as in the treatment of major bone defects and myocardial infarction, MSC has shown a therapeutic effect other than direct hematopoiesis support in hematopoietic reconstruction. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73(SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. Manufacturing of MSC for clinical trials is also an important aspect as their differentiation, homing and Immunomodulatory properties may differ. Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel therapy for GVHD and other autoimmune disorders. Since the cells by themselves are non-immunogenic, tissue matching between MSC donor and recipient is not essential and, MSC may be the first cell type able to be used as an “off-the-shelf” therapeutic product. Following a successful transplantation, the migration of MSC to the site of injury refers to the involvement of chemokines and chemokine receptors of respective specificity. It has been demonstrated that cultured MSCs have the ability to engraft into healthy as well as injured tissue and can differentiate into several cell types in vivo, which facilitates MSC to be an ideal tool for regenerative therapy in different disease types. However, some observations have raised questions about the limitations for proper use of MSC considering some critical factors that warn regular clinical use. PMID:23671814

  17. Differentiation of pluripotent stem cells for regenerative medicine.

    PubMed

    Li, Ke; Kong, Yan; Zhang, Mingliang; Xie, Fei; Liu, Peng; Xu, Shaohua

    2016-02-26

    A long-standing goal in regenerative medicine is to obtain scalable functional cells on demand to replenish cells lost in various conditions, including relevant diseases, injuries, and aging. As an unlimited cell source, pluripotent stem cells (PSCs) are invaluable for regenerative medicine, because they have the potential to give rise to any cell type in an organism. For therapeutic purposes, it is important to develop specific approach to directing PSC differentiation towards desired cell types efficiently. Through directed differentiation, PSCs could give rise to scalable, clinically relevant cells for in vivo transplantation, as well as for studying diseases in vitro and discovering drugs to treat them. Over the past few years, significant progress has been made in directing differentiation of PSCs into a variety of cell types. In this review, we discuss recent progress in directed differentiation of PSCs, clinical translation of PSC-based cell replacement therapies, and remaining challenges.

  18. Derivation and application of pluripotent stem cells for regenerative medicine.

    PubMed

    Wang, Jiaqiang; Zhou, Qi

    2016-06-01

    Pluripotent stem cells (PSCs) are cells that can differentiate into any type of cells in the body, therefore have valuable promise in regenerative medicine of cell replacement therapies and tissue/organ engineering. PSCs can be derived either from early embryos or directly from somatic cells by epigenetic reprogramming that result in customized cells from patients. Here we summarize the methods of deriving PSCs, the various types of PSCs generated with different status, and their versatile applications in both clinical and embryonic development studies. We also discuss an intriguing potential application of PSCs in constructing tissues/organs in large animals by interspecies chimerism. All these emerging findings are likely to contribute to the breakthroughs in biological research and the prosperous prospects of regenerative medicine.

  19. Induced pluripotent stem cells: developmental biology to regenerative medicine.

    PubMed

    Nelson, Timothy J; Martinez-Fernandez, Almudena; Terzic, Andre

    2010-12-01

    Nuclear reprogramming of somatic cells with ectopic stemness factors to bioengineer pluripotent autologous stem cells signals a new era in regenerative medicine. The study of developmental biology has provided a roadmap for cardiac differentiation from embryonic tissue formation to adult heart muscle rejuvenation. Understanding the molecular mechanisms of stem-cell-derived cardiogenesis enables the reproducible generation, isolation, and monitoring of progenitors that have the capacity to recapitulate embryogenesis and differentiate into mature cardiac tissue. With the advent of induced pluripotent stem (iPS) cell technology, patient-specific stem cells provide a reference point to systematically decipher cardiogenic differentiation through discrete stages of development. Interrogation of iPS cells and their progeny from selected cohorts of patients is an innovative approach towards uncovering the molecular mechanisms of disease. Thus, the principles of cardiogenesis can now be applied to regenerative medicine in order to optimize personalized therapeutics, diagnostics, and discovery-based science for the development of novel clinical applications.

  20. Trends in the stem cell and regenerative medicine industry.

    PubMed

    Ilic, Dusko

    2012-09-01

    The World Stem Cell Regenerative Medicine Congress series, now in its 7th year, is organized annually in the USA, Europe and Asia by Terrapinn, a business media company with its head office in London, and has grown over the last several years into the largest and probably the most important strategic stem cell conference where regulators, investors, big pharma, and small and medium enterprises gather to share and create synergy in developing and commercializing stem cell applications. The conference, held in London on 21-23 May 2012, only confirmed that this series is the meeting to attend if you want to get a clear understanding of trends in the stem cell and regenerative medicine industry.

  1. Potential Therapeutic Strategies of Regenerative Medicine for Renal Failure.

    PubMed

    Mata-Miranda, Monica Maribel; Delgado-Macuil, Raul Jacobo; Rojas-Lopez, Marlon; Martinez-Flores, Ricardo; Vazquez-Zapien, Gustavo Jesus

    2017-03-17

    Kidney diseases are a public health problem worldwide; the mortality rate is between 50 and 80%. Available therapies include replacement function by dialysis or transplant, associated with a high morbidity and mortality; kidney transplantation is limited by the shortage of donor organs, immune rejection and lifelong treatment with immunosuppressive. Likewise, none of these treatments compensates all kidney functions. There is a great concern in developing more effective therapies with the ability to replace the wide range of renal functions, so that, new researches on developing therapeutic strategies have focused on regenerative medicine, science that includes artificial creation of tissues and organs, in order to repair or replace a tissue or organ function. The aim of this paper is to review the new advances in regenerative medicine strategies for treatment of renal failure. Generally, regenerative medicine comprises two therapeutic strategies: cell therapy and tissue engineering. Cell therapy techniques depend on cell and tissue culture, with the aim to grow specific cells that will replace morphological structures, tissues and functions. In this area, some investigations that include the use of stem cells have been carried out. Tissue engineering complements cell therapy combining techniques of biological sciences and engineering to create structures and devices as scaffolds, matrices or biocompatible materials, which alone or in combination will give support and facilitate the repair of damaged tissue. Even though there is a great advance in regenerative medicine strategies, we are far from using any of its techniques on health institutions, due to it is necessary to evaluate side effects, biodistribution, dosage, type of administration, vehicle of cell therapy, as well as the evaluation of response time and long-term studies, among other studies.

  2. Stem Cell, Regenerative Medicine and Cancer | Center for Cancer Research

    Cancer.gov

    Of the estimated trillion cells that build up our bodies, only a little number can self-renew and give rise to many different cell types. These unspecialized cells are called stem cells. Stem cell division and differentiation is fundamental to the development of the mature organism. Stem cells have recently attracted significant attention largely due to their potential medical benefits in the fields of therapeutic cloning and regenerative medicine.

  3. On the Genealogy of Tissue Engineering and Regenerative Medicine

    PubMed Central

    2015-01-01

    In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed. PMID:25343302

  4. It's about change...regenerative medicine in the Obama era.

    PubMed

    Klein, Robert N; Doyle, Jim; Siegel, Bernard

    2009-01-01

    During his campaign, US President-elect Obama pledged to use an executive order to overturn federal-funding limits on research into human embryos that are created during fertility treatments imposed by President Bush. Robert Klein, Chairman of the Governing Board of California's stem cell funding agency, Governor Jim Doyle, and Bernard Siegel, Executive Director of the Genetics Policy Institute, discuss the implications of the new administration for regenerative medicine research in the USA.

  5. On the genealogy of tissue engineering and regenerative medicine.

    PubMed

    Kaul, Himanshu; Ventikos, Yiannis

    2015-04-01

    In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.

  6. Arrayed cellular environments for stem cells and regenerative medicine.

    PubMed

    Titmarsh, Drew M; Chen, Huaying; Wolvetang, Ernst J; Cooper-White, Justin J

    2013-02-01

    The behavior and composition of both multipotent and pluripotent stem cell populations are exquisitely controlled by a complex, spatiotemporally variable interplay of physico-chemical, extracellular matrix, cell-cell interaction, and soluble factor cues that collectively define the stem cell niche. The push for stem cell-based regenerative medicine models and therapies has fuelled demands for increasingly accurate cellular environmental control and enhanced experimental throughput, driving an evolution of cell culture platforms away from conventional culture formats toward integrated systems. Arrayed cellular environments typically provide a set of discrete experimental elements with variation of one or several classes of stimuli across elements of the array. These are based on high-content/high-throughput detection, small sample volumes, and multiplexing of environments to increase experimental parameter space, and can be used to address a range of biological processes at the cell population, single-cell, or subcellular level. Arrayed cellular environments have the capability to provide an unprecedented understanding of the molecular and cellular events that underlie expansion and specification of stem cell and therapeutic cell populations, and thus generate successful regenerative medicine outcomes. This review focuses on recent key developments of arrayed cellular environments and their contribution and potential in stem cells and regenerative medicine.

  7. Regenerative medicine in Europe: global competition and innovation governance.

    PubMed

    Hogarth, Stuart; Salter, Brian

    2010-11-01

    Leading European nations with strong biotech sectors, such as the UK and Germany, are investing heavily in regenerative medicine, seeking competitive advantage in this emerging sector. However, in the broader biopharmaceutical sector, the EU is outperformed by the USA on all metrics, reflecting longstanding problems: limited venture capital finance, a fragmented patent system, and relatively weak relations between academia and industry. The current global downturn has exacerbated these difficulties. The crisis comes at a time when the EU is reframing its approach to the governance of innovation and renewing its commitment to the goal of making Europe the leading player in the global knowledge economy. If the EU is to gain a competitive advantage in the regenerative medicine sector then it must coordinate a complex multilevel governance framework that encompasses the EU, member states and regional authorities. This article takes stock of Europe's current competitive position within the global bioeconomy, drawing on a variety of metrics in the three intersecting spheres of innovation governance: science, market and society. These data then provide a platform for reviewing the problems of innovation governance faced by the EU and the strategic choices that have to be confronted in the regenerative medicine sector.

  8. Planarians: an In Vivo Model for Regenerative Medicine.

    PubMed

    Karami, Ali; Tebyanian, Hamid; Goodarzi, Vahabodin; Shiri, Sajad

    2015-11-01

    The emergence of regenerative medicine has raised the hope of treating an extraordinary range of disease and serious injuries. Understanding the processes of cell proliferation, differentiation and pattern formation in regenerative organisms could help find ways to enhance the poor regenerative abilities shown by many other animals, including humans. Recently, planarians have emerged as an attractive model in which to study regeneration. These animals are considering as in vivo plate, during which we can study the behavior and characristics of stem cells in their own niche. A variety of characteristic such as: simplicity, easy to manipulate experimentally, the existence of more than 100 years of literature, makes these animals an extraordinary model for regenerative medicine researches. Among planarians free-living freshwater hermaphrodite Schmidtea mediterranea has emerged as a suitable model system because it displays robust regenerative properties and, unlike most other planarians, it is a stable diploid with a genome size of about 4.8×10(8) base pairs, nearly half that of other common planarians. Planarian regeneration involves two highly flexible systems: pluripotent neoblasts that can generate any new cell type and muscle cells that provide positional instructions for the regeneration of anybody region. neoblasts represent roughly 25~30 percent of all planarian cells and are scattered broadly through the parenchyma, being absent only from the animal head tips and the pharynx. Two models for neo-blast specification have been proposed; the naive model posits that all neoblasts are stem cells with the same potential and are a largely homogeneous population.

  9. Design, clinical translation and immunological response of biomaterials in regenerative medicine

    NASA Astrophysics Data System (ADS)

    Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

    2016-07-01

    The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure-function relationships of cell-material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

  10. Carbon nanotubes: directions and perspectives in oral regenerative medicine.

    PubMed

    Martins-Júnior, P A; Alcântara, C E; Resende, R R; Ferreira, A J

    2013-07-01

    One of the main goals of bone tissue engineering is to identify and develop new biomaterials and scaffolds for structural support and controlled cell growth, which allow for formation or replacement of bone tissue. Recently, carbon nanotubes (CNT) have emerged as a potential candidate for bone tissue engineering. CNT present remarkable mechanical, thermal, and electrical properties with easy functionalization capability and biocompatibility. In oral regenerative medicine, bone reconstruction is an essential requirement for functional rehabilitation of the stomatognathic system. Autologous bone still represents the gold standard graft material for bone reconstruction. However, the small amounts of bone available in donor regions, together with the high costs of surgeries, are critical aspects that hinder the selection of this procedure. Thus, CNT alone or combined with biopolymers have promise to be used as novel potential biomaterials for the restoration of bone defects. Indeed, recent evidence demonstrates CNT to be a feasible material that can increase the formation of bone in tooth sockets of rats. The purpose of this review is to summarize the recent developments in bone repair/regeneration with CNT or CNT-based composites. We further provide an overview of bone tissue engineering and current applications of biomaterials, especially of CNT, to enhance bone regeneration.

  11. Mechanical cues in orofacial tissue engineering and regenerative medicine.

    PubMed

    Brouwer, Katrien M; Lundvig, Ditte M S; Middelkoop, Esther; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-01-01

    Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of tissues and organs in conditions such as birth defects or after injury. A crucial factor in cell differentiation, tissue formation, and tissue function is mechanical strain. Regardless of this, mechanical cues are not yet widely used in TE/RM. The effects of mechanical stimulation on cells are not straight-forward in vitro as cellular responses may differ with cell type and loading regime, complicating the translation to a therapeutic protocol. We here give an overview of the different types of mechanical strain that act on cells and tissues and discuss the effects on muscle, and skin and mucosa. We conclude that presently, sufficient knowledge is lacking to reproducibly implement external mechanical loading in TE/RM approaches. Mechanical cues can be applied in TE/RM by fine-tuning the stiffness and architecture of the constructs to guide the differentiation of the seeded cells or the invading surrounding cells. This may already improve the treatment of orofacial clefts and other disorders affecting soft tissues. © 2015 by the Wound Healing Society.

  12. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

    PubMed

    Nowakowski, Adam; Walczak, Piotr; Janowski, Miroslaw; Lukomska, Barbara

    2015-10-01

    Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented.

  13. Regulators of pluripotency and their implications in regenerative medicine

    PubMed Central

    El-Badawy, Ahmed; El-Badri, Nagwa

    2015-01-01

    The ultimate goal of regenerative medicine is to replace damaged tissues with new functioning ones. This can potentially be accomplished by stem cell transplantation. While stem cell transplantation for blood diseases has been increasingly successful, widespread application of stem cell therapy in the clinic has shown limited results. Despite successful efforts to refine existing methodologies and to develop better ones for reprogramming, clinical application of stem cell therapy suffers from issues related to the safety of the transplanted cells, as well as the low efficiency of reprogramming technology. Better understanding of the underlying mechanism(s) involved in pluripotency should accelerate the clinical application of stem cell transplantation for regenerative purposes. This review outlines the main decision-making factors involved in pluripotency, focusing on the role of microRNAs, epigenetic modification, signaling pathways, and toll-like receptors. Of special interest is the role of toll-like receptors in pluripotency, where emerging data indicate that the innate immune system plays a vital role in reprogramming. Based on these data, we propose that nongenetic mechanisms for reprogramming provide a novel and perhaps an essential strategy to accelerate application of regenerative medicine in the clinic. PMID:25960670

  14. Human dental pulp stem cells: Applications in future regenerative medicine.

    PubMed

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-06-26

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine.

  15. Human dental pulp stem cells: Applications in future regenerative medicine

    PubMed Central

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-01-01

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine. PMID:26131314

  16. Amphibians as research models for regenerative medicine

    PubMed Central

    Song, Fengyu; Li, Bingbing

    2010-01-01

    The ability to regenerate bone across a critical size defect would be a marked clinical advance over current methods for dealing with such structural gaps. Here, we briefly review the development of limb bones and the mandible, the regeneration of urodele limbs after amputation, and present evidence that urodele and anuran amphibians represent a valuable research model for the study of segment defect regeneration in both limb bones and mandible. PMID:21197215

  17. Regenerative Medicine and Restoration of Joint Function

    DTIC Science & Technology

    2014-12-01

    produced during the heat treatment process. A variety of structures have been made to assess the role of macro- size conformal channels on mechanical...the same capacity as bovine chondrocytes to induce redifferentiation. 6b. Identify factor(s) present in conditioned media of co-cultures using mass ...differentiating cells to identify the optimal time to evaluate the conditioned media by mass spectroscopy. We observed that gene expression levels of

  18. Regenerative medicine using dental pulp stem cells for liver diseases

    PubMed Central

    Ohkoshi, Shogo; Hara, Hajime; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko

    2017-01-01

    Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review. PMID:28217369

  19. Regenerative medicine using dental pulp stem cells for liver diseases.

    PubMed

    Ohkoshi, Shogo; Hara, Hajime; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko

    2017-02-06

    Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.

  20. Regenerative medicine for the kidney: stem cell prospects & challenges

    PubMed Central

    2013-01-01

    The kidney has key roles in maintaining human health. There is an escalating medical crisis in nephrology as growing numbers of patients suffer from kidney diseases that culminate in organ failure. While dialysis and transplantation provide life-saving treatments, these therapies are rife with limitations and place significant burdens on patients and healthcare systems. It has become imperative to find alternative ways to treat existing kidney conditions and preemptive means to stave off renal dysfunction. The creation of innovative medical approaches that utilize stem cells has received growing research attention. In this review, we discuss the regenerative and maladaptive cellular responses that occur during acute and chronic kidney disease, the emerging evidence about renal stem cells, and some of the issues that lie ahead in bridging the gap between basic stem cell biology and regenerative medicine for the kidney. PMID:23688352

  1. Regenerative medicine: advances in new methods and technologies.

    PubMed

    Park, Dong-Hyuk; Eve, David J

    2009-11-01

    The articles published in the journal Cell Transplantation - The Regenerative Medicine Journal over the last two years reveal the recent and future cutting-edge research in the fields of regenerative and transplantation medicine. 437 articles were published from 2007 to 2008, a 17% increase compared to the 373 articles in 2006-2007. Neuroscience was still the most common section in both the number of articles and the percentage of all manuscripts published. The increasing interest and rapid advance in bioengineering technology is highlighted by tissue engineering and bioartificial organs being ranked second again. For a similar reason, the methods and new technologies section increased significantly compared to the last period. Articles focusing on the transplantation of stem cell lineages encompassed almost 20% of all articles published. By contrast, the non-stem cell transplantation group which is made up primarily of islet cells, followed by biomaterials and fetal neural tissue, etc. comprised less than 15%. Transplantation of cells pre-treated with medicine or gene transfection to prolong graft survival or promote differentiation into the needed phenotype, was prevalent in the transplantation articles regardless of the kind of cells used. Meanwhile, the majority of non-transplantation-based articles were related to new devices for various purposes, characterization of unknown cells, medicines, cell preparation and/or optimization for transplantation (e.g. isolation and culture), and disease pathology.

  2. The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models

    PubMed Central

    Tashiro, Syoichi; Nakamura, Masaya; Okano, Hideyuki

    2017-01-01

    Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury (SCI). By contrast, there are still only a few studies have focused on the treatment of the chronically injured spinal cord, in which cell-based regenerative medicine seems less effective. Since the majority of SCI patients are in the chronic phase, representing a major challenge for the clinical application of cell-based regenerative medicine. Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized, there had been very few studies involving rehabilitative treatments to date. In a recent study, we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI, not only in additive but also in synergistic manner. Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy, the mechanism underlying the effects remain unsolved. In this review article, we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models. PMID:28250738

  3. Regenerative medicine and tissue engineering in orthopaedic surgery.

    PubMed

    Ivkovic, Alan; Marijanovic, Inga; Hudetz, Damir; Porter, Ryan M; Pecina, Marko; Evans, Christopher H

    2011-06-01

    Orthopedic surgery is going through a serious paradigm shift; instead of simply replacing damaged tissues with prosthetic or allograft material, the aim is to regenerate them. This endeavor has generated the field of regenerative orthopaedics, an increasingly expanding area of research with hopes of providing new and better treatments for diseases and injuries affecting the musculoskeletal system. As part of this process, we are witnessing a substantial accumulation of new cellular and molecular insights into connective tissue function, coupled with emerging new concepts in stem cell biology and scaffolding technologies. Indeed, any successful strategy to regenerate musculoskeletal tissues can be portrayed as an intricate interplay between the three main constituents of the regenerative system: cells, environment and scaffolds. This review is not meant to be exhaustive and comprehensive, but aims to highlight concepts and key advances in the field of regenerative orthopaedics and tissue engineering, as well as to present current possibilities for clinical translation.

  4. Nonhuman primate models in translational regenerative medicine.

    PubMed

    Daadi, Marcel M; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E

    2014-12-01

    Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell-based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell-derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena.

  5. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells.

    PubMed

    Xiao, Li; Nasu, Masanori

    2014-01-01

    Adult mesenchymal stem cells (MSCs) and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and mesenchymal stem cells from gingiva (GMSCs). They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin-pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.

  6. Chitosan and fish collagen as biomaterials for regenerative medicine.

    PubMed

    Hayashi, Yoshihiko; Yamada, Shizuka; Yanagi Guchi, Kajiro; Koyama, Zenya; Ikeda, Takeshi

    2012-01-01

    This chapter focuses and reviews on the characteristics and biomedical application of chitosan and collagen from marine products and advantages and disadvantages of regeneration medicine. The understanding of the production processes of chitosan and collagen and the conformation of these biomaterials are indispensable for promoting the theoretical and practical availability. The initial inflammatory reactions associated with chitosan application to hard and soft tissues need to be controlled before it can be considered for clinical application as scaffold. Further, as chitosan takes too long for biodegradation in vivo, generally it is not suitable for the scaffold for degenerative medicine in especially dental pulp tissue. The collagen extract from the scales of tropical fish has been reported to have a degeneration temperature of 35°C. The properties of biocompatibility and biodegradation of fish atelocollagen are suitable for the scaffold in regenerative medicine.

  7. Cell/tissue processing information system for regenerative medicine.

    PubMed

    Iwayama, Daisuke; Yamato, Masayuki; Tsubokura, Tetsuya; Takahashi, Minoru; Okano, Teruo

    2016-11-01

    When conducting clinical studies of regenerative medicine, compliance to good manufacturing practice (GMP) is mandatory, and thus much time is needed for manufacturing and quality management. It is therefore desired to introduce the manufacturing execution system (MES), which is being adopted by factories manufacturing pharmaceutical products. Meanwhile, in manufacturing human cell/tissue processing autologous products, it is necessary to protect patients' personal information, prevent patients from being identified and obtain information for cell/tissue identification. We therefore considered it difficult to adopt conventional MES to regenerative medicine-related clinical trials, and so developed novel software for production/quality management to be used in cell-processing centres (CPCs), conforming to GMP. Since this system satisfies the requirements of regulations in Japan and the USA for electronic records and electronic signatures (ER/ES), the use of ER/ES has been allowed, and the risk of contamination resulting from the use of recording paper has been eliminated, thanks to paperless operations within the CPC. Moreover, to reduce the risk of mix-up and cross-contamination due to contact during production, we developed a touchless input device with built-in radio frequency identification (RFID) reader-writer devices and optical sensors. The use of this system reduced the time to prepare and issue manufacturing instructions by 50% or more, compared to the conventional handwritten system. The system contributes to producing more large-scale production and to reducing production costs for cell and tissue products in regenerative medicine. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Stem cells, regenerative medicine, and animal models of disease.

    PubMed

    Steindler, Dennis A

    2007-01-01

    The field of stem cell biology and regenerative medicine is rapidly moving toward translation to clinical practice, and in doing so has become even more dependent on animal donors and hosts for generating cellular reagents and assaying their potential therapeutic efficacy in models of human disease. Advances in cell culture technologies have revealed a remarkable plasticity of stem cells from embryonic and adult tissues, and transplantation models are now needed to test the ability of these cells to protect at-risk cells and replace cells lost to injury or disease. With such a mandate, issues related to acceptable sources and controversial (e.g., chimeric) models have challenged the field to provide justification of their potential efficacy before the passage of new restrictions that may curb anticipated breakthroughs. Progress from the use of both in vitro and in vivo regenerative medicine models already offers hope both for the facilitation of stem cell phenotyping in recursive gene expression profile models and for the use of stem cells as powerful new therapeutic reagents for cancer, stroke, Parkinson's, and other challenging human diseases that result in movement disorders. This article describes research in support of the following three objectives: (1) To discover the best stem or progenitor cell in vitro protocols for isolating, expanding, and priming these cells to facilitate their massive propagation into just the right type of neuronal precursor cell for protection or replacement protocols for brain injury or disease, including those that affect movement such as Parkinson's disease and stroke; (2) To discover biogenic factors--compounds that affect stem/progenitor cells (e.g., from high-throughput screening and other bioassay approaches)--that will encourage reactive cell genesis, survival, selected differentiation, and restoration of connectivity in central nervous system movement and other disorders; and (3) To establish the best animal models of human

  9. Adipose Tissue-Derived Stem Cells in Regenerative Medicine.

    PubMed

    Frese, Laura; Dijkman, Petra E; Hoerstrup, Simon P

    2016-07-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted.

  10. Adipose Tissue-Derived Stem Cells in Regenerative Medicine

    PubMed Central

    Frese, Laura; Dijkman, Petra E.; Hoerstrup, Simon P.

    2016-01-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted. PMID:27721702

  11. Cell delivery in regenerative medicine: the cell sheet engineering approach.

    PubMed

    Yang, Joseph; Yamato, Masayuki; Nishida, Kohji; Ohki, Takeshi; Kanzaki, Masato; Sekine, Hidekazu; Shimizu, Tatsuya; Okano, Teruo

    2006-11-28

    Recently, cell-based therapies have developed as a foundation for regenerative medicine. General approaches for cell delivery have thus far involved the use of direct injection of single cell suspensions into the target tissues. Additionally, tissue engineering with the general paradigm of seeding cells into biodegradable scaffolds has also evolved as a method for the reconstruction of various tissues and organs. With success in clinical trials, regenerative therapies using these approaches have therefore garnered significant interest and attention. As a novel alternative, we have developed cell sheet engineering using temperature-responsive culture dishes, which allows for the non-invasive harvest of cultured cells as intact sheets along with their deposited extracellular matrix. Using this approach, cell sheets can be directly transplanted to host tissues without the use of scaffolding or carrier materials, or used to create in vitro tissue constructs via the layering of individual cell sheets. In addition to simple transplantation, cell sheet engineered constructs have also been applied for alternative therapies such as endoscopic transplantation, combinatorial tissue reconstruction, and polysurgery to overcome limitations of regenerative therapies and cell delivery using conventional approaches.

  12. Bringing regenerative medicines to the clinic: the future for regulation and reimbursement.

    PubMed

    Bubela, Tania; McCabe, Christopher; Archibald, Peter; Atkins, Harold; Bradshaw, Steven E; Kefalas, Panos; Mujoomdar, Michelle; Packer, Claire; Piret, James; Raxworthy, Mike; Soares, Marta; Viswanathan, Sowmya

    2015-01-01

    Significant investments in regenerative medicine necessitate discussion to align evidentiary requirements and decision-making considerations from regulatory, health system payer and developer perspectives. Only with coordinated efforts will the potential of regenerative medicine be realized. We report on discussions from two workshops sponsored by NICE, University of Alberta, Cell Therapy Catapult and Centre for Commercialization of Regenerative Medicine. We discuss methods to support the assessment of value for regenerative medicine products and services and the synergies that exist between market authorization and reimbursement regulations and practices. We discuss the convergence in novel adaptive licensing practices that may promote the development and adoption of novel therapeutics that meet the needs of healthcare payers.

  13. Stem cells and vascular regenerative medicine: A mini review.

    PubMed

    Stoltz, J-F; Bensoussan, D; De Isla, N; Zhang, L; Han, Z; Magdalou, J; Huselstein, C; Ye, J S; Leballe, B; Decot, V; Reppel, L

    2016-01-01

    Most human tissues do not regenerate spontaneously, which is why "cell therapy" are promising alternative treatments. The Principe is simple: patients' or donors' cells are collected and introduced into the injured tissues or organs directly or in a porous 3D material, with or without modification of their properties. This concept of regenerative medicine is an emerging field which can be defined as "the way to improve health and quality of life by restoring, maintaining, or enhancing tissue and organ functions".There is an extraordinarily wide range of opportunities for clinical applications: artheropathies, diabetes, cartilage defects, bone repair, burns, livers or bladder regeneration, organs reconstruction (lung, heart, liver ...) neurodegenerative disorders, sepsis ...  Different stem cells (SC) with different potential can be used and characterised (totipotent, mesenchymal of different origins, especially those present in tissues...). Today it is undeniable that cells like bone marrow, adipose tissue or Wharton Jelly stem cells, are of potential interest for clinical applications because they are easily separated and prepared and no ethical problems are involved in their use.In this paper some potential clinical applications in the vascular field are considered: peripheral arteriopathy in diabetic patients, cardiac insufficiency, traitment of erectile dysfunction, or organ regeneration with liver as example. But the regeneration of tissue or organ is and will remain a challenge for the future development of cell therapy. Many problems remain to be solved that could lead to the development of innovative strategies to facilitate cell differentiation, increase the yield of cells and ensure a standardised product, overcome the risks of teratogenic effects and/or immune reactions, enable grafting via direct cell or biotissue transplantation and avoid legal issues involved in national regulations.

  14. Inflammation-sensitive in situ smart scaffolding for regenerative medicine.

    PubMed

    Patra, Hirak K; Sharma, Yashpal; Islam, Mohammad Mirazul; Jafari, Mohammad Javad; Murugan, N Arul; Kobayashi, Hisatoshi; Turner, Anthony P F; Tiwari, Ashutosh

    2016-10-06

    gated inflammation-sensitive smart biomaterials for advanced tissue regeneration and regenerative medicine.

  15. Development of a Cell Sheet Transportation Technique for Regenerative Medicine

    PubMed Central

    Oie, Yoshinori; Nozaki, Takayuki; Takayanagi, Hiroshi; Hara, Susumu; Hayashi, Ryuhei; Takeda, Shizu; Mori, Keisuke; Moriya, Noboru; Soma, Takeshi; Tsujikawa, Motokazu; Saito, Kazuo

    2014-01-01

    Purpose: A transportation technique for cell sheets is necessary to standardize regenerative medicine. The aim of this article is to develop and evaluate a new transportation technique for cell sheets. Material and Methods: We developed a transportation container with three basic functions: the maintenance of interior temperature, air pressure, and sterility. The interior temperature and air pressure were monitored by a recorder. Human oral mucosal epithelial cells obtained from two healthy volunteers were cultured on temperature-responsive culture dishes. The epithelial cell sheets were transported via an airplane between the Osaka University and Tohoku University using the developed cell transportation container. Histological and immunohistochemical analyses and flow cytometric analyses for cell viability and cell purity were performed for the cell sheets before and 12 h after transportation to assess the influence of transportation on the cell sheets. Sterility tests and screening for endotoxin and mycoplasma in the cell sheets were performed before and after transportation. Results: During transportation via an airplane, the temperature inside the container was maintained above 32°C, and the changes in air pressure remained within 10 hPa. The cell sheets were well stratified and successfully harvested before and after transportation. The expression patterns of keratin 3/76, p63, and MUC16 were equivalent before and after transportation. However, the expression of ZO-1 in the cell sheet after transportation was slightly weaker than that before transportation. The cell viability was 72.0% before transportation and 77.3% after transportation. The epithelial purity was 94.6% before transportation and 87.9% after transportation. Sterility tests and screening for endotoxin and mycoplasma were negative for all cell sheets. Conclusion: The newly developed transportation technique for air travel is essential technology for regenerative medicine and promotes the

  16. Development of a cell sheet transportation technique for regenerative medicine.

    PubMed

    Oie, Yoshinori; Nozaki, Takayuki; Takayanagi, Hiroshi; Hara, Susumu; Hayashi, Ryuhei; Takeda, Shizu; Mori, Keisuke; Moriya, Noboru; Soma, Takeshi; Tsujikawa, Motokazu; Saito, Kazuo; Nishida, Kohji

    2014-05-01

    A transportation technique for cell sheets is necessary to standardize regenerative medicine. The aim of this article is to develop and evaluate a new transportation technique for cell sheets. We developed a transportation container with three basic functions: the maintenance of interior temperature, air pressure, and sterility. The interior temperature and air pressure were monitored by a recorder. Human oral mucosal epithelial cells obtained from two healthy volunteers were cultured on temperature-responsive culture dishes. The epithelial cell sheets were transported via an airplane between the Osaka University and Tohoku University using the developed cell transportation container. Histological and immunohistochemical analyses and flow cytometric analyses for cell viability and cell purity were performed for the cell sheets before and 12 h after transportation to assess the influence of transportation on the cell sheets. Sterility tests and screening for endotoxin and mycoplasma in the cell sheets were performed before and after transportation. During transportation via an airplane, the temperature inside the container was maintained above 32°C, and the changes in air pressure remained within 10 hPa. The cell sheets were well stratified and successfully harvested before and after transportation. The expression patterns of keratin 3/76, p63, and MUC16 were equivalent before and after transportation. However, the expression of ZO-1 in the cell sheet after transportation was slightly weaker than that before transportation. The cell viability was 72.0% before transportation and 77.3% after transportation. The epithelial purity was 94.6% before transportation and 87.9% after transportation. Sterility tests and screening for endotoxin and mycoplasma were negative for all cell sheets. The newly developed transportation technique for air travel is essential technology for regenerative medicine and promotes the standardization and spread of regenerative therapies.

  17. Stem Cell Banking for Regenerative and Personalized Medicine.

    PubMed

    Harris, David T

    2014-02-26

    Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today's intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source.

  18. Three-dimensional bioprinting in tissue engineering and regenerative medicine.

    PubMed

    Gao, Guifang; Cui, Xiaofeng

    2016-02-01

    With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

  19. Implications of mesenchymal stem cells in regenerative medicine.

    PubMed

    Kariminekoo, Saber; Movassaghpour, Aliakbar; Rahimzadeh, Amirbahman; Talebi, Mehdi; Shamsasenjan, Karim; Akbarzadeh, Abolfazl

    2016-05-01

    Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Self-renewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-β, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs.

  20. The Hematopoietic System in the Context of Regenerative Medicine

    PubMed Central

    Porada, Christopher D.; Atala, Anthony J.; Almeida-Porada, Graça

    2015-01-01

    Hematopoietic stem cells (HSC) represent the prototype stem cell within the body. Since their discovery, HSC have been the focus of intensive research, and have proven invaluable clinically to restore hematopoiesis following inadvertent radiation exposure and following radio/chemotherapy to eliminate hematologic tumors. While they were originally discovered in the bone marrow, HSC can also be isolated from umbilical cord blood and can be “mobilized” peripheral blood, making them readily available in relatively large quantities. While their ability to repopulate the entire hematopoietic system would already guarantee HSC a valuable place in regenerative medicine, the finding that hematopoietic chimerism can induce immunological tolerance to solid organs and correct autoimmune diseases has dramatically broadened their clinical utility. The demonstration that these cells, through a variety of mechanisms, can also promote repair/regeneration of non-hematopoietic tissues as diverse as liver, heart, and brain has further increased their clinical value. The goal of this review is to provide the reader with a brief glimpse into the remarkable potential HSC possess, and to highlight their tremendous value as therapeutics in regenerative medicine. PMID:26319943

  1. Macro and Microfluidic Flows for Skeletal Regenerative Medicine

    PubMed Central

    Riehl, Brandon D.; Lim, Jung Yul

    2012-01-01

    Fluid flow has a great potential as a cell stimulatory tool for skeletal regenerative medicine, because fluid flow-induced bone cell mechanotransduction in vivo plays a critical role in maintaining healthy bone homeostasis. Applications of fluid flow for skeletal regenerative medicine are reviewed at macro and microscale. Macroflow in two dimensions (2D), in which flow velocity varies along the normal direction to the flow, has explored molecular mechanisms of bone forming cell mechanotransduction responsible for flow-regulated differentiation, mineralized matrix deposition, and stem cell osteogenesis. Though 2D flow set-ups are useful for mechanistic studies due to easiness in in situ and post-flow assays, engineering skeletal tissue constructs should involve three dimensional (3D) flows, e.g., flow through porous scaffolds. Skeletal tissue engineering using 3D flows has produced promising outcomes, but 3D flow conditions (e.g., shear stress vs. chemotransport) and scaffold characteristics should further be tailored. Ideally, data gained from 2D flows may be utilized to engineer improved 3D bone tissue constructs. Recent microfluidics approaches suggest a strong potential to mimic in vivo microscale interstitial flows in bone. Though there have been few microfluidics studies on bone cells, it was demonstrated that microfluidic platform can be used to conduct high throughput screening of bone cell mechanotransduction behavior under biomimicking flow conditions. PMID:24710552

  2. Implementing tissue engineering and regenerative medicine solutions in medical implants.

    PubMed

    Ye, Dongxia; Peramo, Antonio

    2014-01-01

    Surgical implants are widely used in the medical field but their long-term performance is limited due to failure of integration with tissues. This manuscript describes very well-known problems associated with implants and discusses novel solutions used in tissue engineering and regenerative medicine that can be implemented in this uncommonly discussed medical area. General and medical literature describing modifications of medical and surgical implants, biofunctionalization, tissue engineering and regenerative medicine. Procedures for surgical implantation have grown substantially in the last few decades and provided improved quality of life for patients, regardless of area of implantation and device type and purpose. In general, implants fail because of lack of long-term integration with the surrounding tissues. Implant manufacturers have not addressed implant failure from the point of view of biointegration. In addition, some medical practitioners are inclined to treat implant failure by using anti-infection methods to prevent bacterial adhesion. However, both approaches are conceptually limited, as discussed in this manuscript. Implantation in the future will not be limited to medically needed procedures but also to a growing number of cosmetic body transformation procedures, which may include perceived 'improved implant functions' over natural tissues or organs. An additional trend is that implant procedures are being progressively performed in younger individuals. Current implants generally do not allow the physician to have controlled long-term access to internal tissues in contact with the implants, for example to release specific compounds when medically needed to the problem area.

  3. Multiscale Inorganic Hierarchically Materials: Towards an Improved Orthopaedic Regenerative Medicine.

    PubMed

    Ruso, Juan M; Sartuqui, Javier; Messina, Paula V

    2015-01-01

    Bone is a biologically and structurally sophisticated multifunctional tissue. It dynamically responds to biochemical, mechanical and electrical clues by remodelling itself and accordingly the maximum strength and toughness are along the lines of the greatest applied stress. The challenge is to develop an orthopaedic biomaterial that imitates the micro- and nano-structural elements and compositions of bone to locally match the properties of the host tissue resulting in a biologically fixed implant. Looking for the ideal implant, the convergence of life and materials sciences occurs. Researchers in many different fields apply their expertise to improve implantable devices and regenerative medicine. Materials of all kinds, but especially hierarchical nano-materials, are being exploited. The application of nano-materials with hierarchical design to calcified tissue reconstructive medicine involve intricate systems including scaffolds with multifaceted shapes that provides temporary mechanical function; materials with nano-topography modifications that guarantee their integration to tissues and that possesses functionalized surfaces to transport biologic factors to stimulate tissue growth in a controlled, safe, and rapid manner. Furthermore materials that should degrade on a timeline coordinated to the time that takes the tissues regrow, are prepared. These implantable devices are multifunctional and for its construction they involve the use of precise strategically techniques together with specific material manufacturing processes that can be integrated to achieve in the design, the required multifunctionality. For such reasons, even though the idea of displacement from synthetic implants and tissue grafts to regenerative-medicine-based tissue reconstruction has been guaranteed for well over a decade, the reality has yet to emerge. In this paper, we examine the recent approaches to create enhanced bioactive materials. Their design and manufacturing procedures as well

  4. Current status of stem cells and regenerative medicine research in Argentina.

    PubMed

    Pitossi, Fernando J; Podhajcer, Osvaldo L

    2014-12-01

    Since Takahashi and Yamanaka demonstrated for the first time that fully differentiated somatic cells can be reprogrammed to a pluripotent state with a small group of transcription factors a revolution erupted in the regenerative medicine field. New advances showing direct differentiation of mature cells increased the excitement of the field. This work describes the present situation of the field in Argentina and the efforts implemented by science authorities to strengthen and push the field forward.

  5. Can regenerative medicine and nanotechnology combine to heal wounds? The search for the ideal wound dressing.

    PubMed

    Zarrintaj, Payam; Moghaddam, Abolfazl Salehi; Manouchehri, Saeed; Atoufi, Zhaleh; Amiri, Anahita; Amirkhani, Mohammad Amir; Nilforoushzadeh, Mohammad Ali; Saeb, Mohammad Reza; Hamblin, Michael R; Mozafari, Masoud

    2017-10-01

    Skin is the outermost covering of the human body and at the same time the largest organ comprising 15% of body weight and 2 m(2) surface area. Skin plays a key role as a barrier against the outer environment depending on its thickness, color and structure, which differ from one site to another. The four major types of problematic wounds include ulcers (diabetic, venous, pressure) and burn wounds. Developing novel dressings helps us to improve the wound healing process in difficult patients. Recent advances in regenerative medicine and nanotechnology are revolutionizing the field of wound healing. Antimicrobial activity, exogenous cell therapy, growth factor delivery, biodegradable and biocompatible matrix construction, all play a role in hi-tech dressing design. In the present review, we discuss how the principles of regenerative medicine and nanotechnology can be combined in innovative wound dressings.

  6. Stem Cell Tracking with Nanoparticles for Regenerative Medicine Purposes: An Overview

    PubMed Central

    Accomasso, Lisa; Gallina, Clara; Turinetto, Valentina; Giachino, Claudia

    2016-01-01

    Accurate and noninvasive stem cell tracking is one of the most important needs in regenerative medicine to determine both stem cell destinations and final differentiation fates, thus allowing a more detailed picture of the mechanisms involved in these therapies. Given the great importance and advances in the field of nanotechnology for stem cell imaging, currently, several nanoparticles have become standardized products and have been undergoing fast commercialization. This review has been intended to summarize the current use of different engineered nanoparticles in stem cell tracking for regenerative medicine purposes, in particular by detailing their main features and exploring their biosafety aspects, the first step for clinical application. Moreover, this review has summarized the advantages and applications of stem cell tracking with nanoparticles in experimental and preclinical studies and investigated present limitations for their employment in the clinical setting. PMID:26839568

  7. Tissue Engineering and Regenerative Medicine in Iran: Current State of Research and Future Outlook.

    PubMed

    Mobini, Sahba; Khanmohammadi, Manijeh; Heidari-Vala, Hamed; Samadikuchaksaraei, Ali; Moshiri, Ali; Kazemnejad, Somaieh

    2015-07-01

    During two decades ago, Iran has exhibited remarkable increase in scientific publication in different aspects including tissue engineering and regenerative medicine (TERM). The field of TERM in Iran dates comes back to the early part of the 1990 and the advent of stem cell researches. Nowadays, Iran is one of the privileged countries in stem cell therapy in the Middle East. The next major milestone in TERM was application and fabrication of scaffolds for tissue engineering in the early 2000s with a focus on engineering bone and cartilage tissue. A good amount of thoughtful works has also yielded prototypes of other tissue substitutes such as nerve conduits, liver, and even heart. However, forward movement to clinical application of these products is still far from offering clinically acceptable solutions. In this study, we have presented a comprehensive review on the efforts of Iranian scientists in different issues of tissue engineering and regenerative medicine field.

  8. Early evaluation and value-based pricing of regenerative medicine technologies.

    PubMed

    Koerber, Florian; Rolauffs, Bernd; Rogowski, Wolf

    2013-11-01

    Since the first pioneering scientists explored the potential of using human cells for therapeutic purposes the branch of regenerative medicine has evolved to become a mature industry. The focus has switched from 'what can be done' to 'what can be commercialized'. Timely health economic evaluation supports successful marketing by establishing the value of a product from a healthcare system perspective. This article reports results from a research project on early health economic evaluation in collaboration with developers, clinicians and manufacturers. We present an approach to determine an early value-based price for a new treatment of cartilage defects of the knee from the area of regenerative medicine. Examples of using evaluation results for the purpose of business planning, market entry, preparing the coverage decision and managed entry are discussed.

  9. Stem cell biology and regenerative medicine for neonatal lung diseases.

    PubMed

    Kang, Martin; Thébaud, Bernard

    2017-09-18

    Lung diseases remain one of the main causes of morbidity and mortality in neonates. Cell therapy and regenerative medicine have the potential to revolutionize the management of life-threatening and debilitating lung diseases that currently lack effective treatments. Over the past decade, the repair capabilities of stem/progenitor cells has been harnessed to prevent/rescue lung damage in experimental neonatal lung diseases. Mesenchymal stromal cells and amnion epithelial cells exert pleiotropic effects and represent ideal therapeutic cells for bronchopulmonary dysplasia, a multifactorial disease. Endothelial progenitor cells are optimally suited to promote lung vascular growth and attenuate pulmonary hypertension in infants with congenital diaphragmatic hernia or a vascular bronchopulmonary dysplasia phenotype. Induced pluripotent stem cells (iPSCs) are one of the most exciting breakthroughs of the past decade. Patient-specific iPSCs can be derived from somatic cells and differentiated into any cell type. iPSCs can be capitalized upon to develop personalized regenerative cell products for surfactant protein deficiencies-lethal lung disorders without treatment-that affect a single gene in a single cell type and thus lend themselves to phenotype-specific cell replacement. While the clinical translation has begun, more needs to be learned about the biology of these repair cells to make this translation successful.Pediatric Research accepted article preview online, 18 September 2017. doi:10.1038/pr.2017.232.

  10. Renal stem cell reprogramming: Prospects in regenerative medicine

    PubMed Central

    Morales, Elvin E; Wingert, Rebecca A

    2014-01-01

    Stem cell therapy is a promising future enterprise for renal replacement in patients with acute and chronic kidney disease, conditions which affect millions worldwide and currently require patients to undergo lifelong medical treatments through dialysis and/or organ transplant. Reprogramming differentiated renal cells harvested from the patient back into a pluripotent state would decrease the risk of tissue rejection and provide a virtually unlimited supply of cells for regenerative medicine treatments, making it an exciting area of current research in nephrology. Among the major hurdles that need to be overcome before stem cell therapy for the kidney can be applied in a clinical setting are ensuring the fidelity and relative safety of the reprogrammed cells, as well as achieving feasible efficiency in the reprogramming processes that are utilized. Further, improved knowledge about the genetic control of renal lineage development is vital to identifying predictable and efficient reprogramming approaches, such as the expression of key modulators or the regulation of gene activity through small molecule mimetics. Here, we discuss several recent advances in induced pluripotent stem cell technologies. We also explore strategies that have been successful in renal progenitor generation, and explore what these methods might mean for the development of cell-based regenerative therapies for kidney disease. PMID:25258667

  11. MiRNA inhibition in tissue engineering and regenerative medicine.

    PubMed

    Beavers, Kelsey R; Nelson, Christopher E; Duvall, Craig L

    2015-07-01

    MicroRNAs (miRNAs) are noncoding RNAs that provide an endogenous negative feedback mechanism for translation of messenger RNA (mRNA) into protein. Single miRNAs can regulate hundreds of mRNAs, enabling miRNAs to orchestrate robust biological responses by simultaneously impacting multiple gene networks. MiRNAs can act as master regulators of normal and pathological tissue development, homeostasis, and repair, which has motivated expanding efforts toward the development of technologies for therapeutically modulating miRNA activity for regenerative medicine and tissue engineering applications. This review highlights the tools currently available for miRNA inhibition and their recent therapeutic applications for improving tissue repair.

  12. miRNA Inhibition in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Beavers, Kelsey R.; Nelson, Christopher E.; Duvall, Craig L.

    2014-01-01

    MicroRNA (miRNA) are noncoding RNA that provide an endogenous negative feedback mechanism for translation of messenger RNA (mRNA) into protein. Single miRNAs can regulate hundreds of mRNAs, enabling miRNAs to orchestrate robust biological responses by simultaneously impacting multiple gene networks. MiRNAs can act as master regulators of normal and pathological tissue development, homeostasis, and repair, which has recently motivated expanding efforts toward development of technologies for therapeutically modulating miRNA activity for regenerative medicine and tissue engineering applications. This review highlights the tools currently available for miRNA inhibition and their recent therapeutic applications for improving tissue repair. PMID:25553957

  13. Preserving human cells for regenerative, reproductive, and transfusion medicine

    PubMed Central

    Asghar, Waseem; Assal, Rami El; Shafiee, Hadi; Anchan, Raymond M.; Demirci, Utkan

    2014-01-01

    Cell cryopreservation enables maintaining cellular life at sub-zero temperatures by slowing down biochemical processes. Various cell types are routinely cryopreserved in modern reproductive, regenerative, and transfusion medicine. Current cell cryopreservation methods involve freezing (slow/rapid) or vitrifying cells in the presence of a cryoprotective agent (CPA). Although these methods are clinically utilized, cryo-injury due to ice crystals, osmotic shock, and CPA toxicity cause loss of cell viability and function. Recent approaches using minimum volume vitrification provide alternatives to the conventional cryopreservation methods. Minimum volume vitrification provides ultra-high cooling and rewarming rates that enable preserving cells without ice crystal formation. Herein, we review recent advances in cell cryopreservation technology and provide examples of techniques that are utilized in oocyte, stem cell, and red blood cell cryopreservation. PMID:24995723

  14. Cell fusion: biological perspectives and potential for regenerative medicine.

    PubMed

    Alvarez-Dolado, Manuel

    2007-01-01

    Cell fusion has emerged as a powerful subject of debate in the last few years. Adult stem cell plasticity and the search for mechanisms to explain this process have led to the "rediscovery" of cell fusion. In nature, cell fusion is a normal process involved in sexual reproduction, tissue formation, and immune response. The recent observation that bone marrow derived cells fuse with several cell types introduces new and provocative questions. In this review, I shall recapitulate what is known about cell fusion and discuss its more controversial aspects. I shall highlight the most exciting open questions; its biological potential; pros and cons; and their implications on stem cell plasticity, regenerative medicine, and development.

  15. Bioengineering Heart Muscle: A Paradigm for Regenerative Medicine

    PubMed Central

    Lui, Kathy O.; Tandon, Nina

    2012-01-01

    The idea of extending the lifetime of our organs is as old as humankind, fueled by major advances in organ transplantation, novel drugs, and medical devices. However, true regeneration of human tissue has becoming increasingly plausible only in recent years. The human heart has always been a focus of such efforts, given its notorious inability to repair itself following injury or disease. We discuss here the emerging bioengineering approaches to regeneration of heart muscle as a paradigm for regenerative medicine. Our focus is on biologically inspired strategies for heart regeneration, knowledge gained thus far about how to make a “perfect” heart graft, and the challenges that remain to be addressed for tissue-engineered heart regeneration to become a clinical reality. We emphasize the need for interdisciplinary research and training, as recent progress in the field is largely being made at the interfaces between cardiology, stem cell science, and bioengineering. PMID:21568715

  16. Regenerative and Rehabilitative Medicine: A Necessary Synergy for Functional Recovery from Volumetric Muscle Loss Injury.

    PubMed

    Greising, Sarah M; Dearth, Christopher L; Corona, Benjamin T

    2016-01-01

    Volumetric muscle loss (VML) is a complex and heterogeneous problem due to significant traumatic or surgical loss of skeletal muscle tissue. The consequences of VML are substantial functional deficits in joint range of motion and skeletal muscle strength, resulting in life-long dysfunction and disability. Traditional physical medicine and rehabilitation paradigms do not address the magnitude of force loss due to VML and related musculoskeletal comorbidities. Recent advancements in regenerative medicine have set forth encouraging and emerging therapeutic options for VML injuries. There is significant potential that combined rehabilitative and regenerative therapies can restore limb and muscle function following VML injury in a synergistic manner. This review presents the current state of the VML field, spanning clinical and preclinical literature, with particular focus on rehabilitation and regenerative medicine in addition to their synergy. Moving forward, multidisciplinary collaboration between clinical and research fields is encouraged in order to continue to improve the treatment of VML injuries and specifically address the encompassing physiology, pathology, and specific needs of this patient population. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel.

  17. Are agricultural and natural sources of bio-products important for modern regenerative medicine? A review.

    PubMed

    Nowacki, Maciej; Nowacka, Katarzyna; Kloskowski, Tomasz; Pokrywczyńska, Marta; Tyloch, Dominik; Rasmus, Marta; Warda, Karolina; Drewa, Tomasz

    2017-05-11

    [b] Abstract Introduction and objectives[/b]. As tissue engineering and regenerative medicine have continued to evolve within the field of biomedicine, the fundamental importance of bio-products has become increasingly apparent. This true not only in cases where they are derived directly from the natural environment, but also when animals and plants are specially bred and cultivated for their production. [b]Objective.[/b] The study aims to present and assess the global influence and importance of selected bio-products in current regenerative medicine via a broad review of the existing literature. In particular, attention is paid to the matrices, substances and grafts created from plants and animals which could potentially be used in experimental and clinical regeneration, or in reconstructive procedures. [b]Summary.[/b] Evolving trends in agriculture are likely to play a key role in the future development of a number of systemic and local medical procedures within tissue engineering and regenerative medicine. This is in addition to the use of bio-products derived from the natural environment which are found to deliver positive results in the treatment of prospective patients.

  18. Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology

    NASA Astrophysics Data System (ADS)

    Pei, Duanqing; Xu, Jianyong; Zhuang, Qiang; Tse, Hung-Fat; Esteban, Miguel A.

    The potential of human embryonic stem cells (ESCs) for regenerative medicine is unquestionable, but practical and ethical considerations have hampered clinical application and research. In an attempt to overcome these issues, the conversion of somatic cells into pluripotent stem cells similar to ESCs, commonly termed nuclear reprogramming, has been a top objective of contemporary biology. More than 40 years ago, King, Briggs, and Gurdon pioneered somatic cell nuclear reprogramming in frogs, and in 1981 Evans successfully isolated mouse ESCs. In 1997 Wilmut and collaborators produced the first cloned mammal using nuclear transfer, and then Thomson obtained human ESCs from in vitro fertilized blastocysts in 1998. Over the last 2 decades we have also seen remarkable findings regarding how ESC behavior is controlled, the importance of which should not be underestimated. This knowledge allowed the laboratory of Shinya Yamanaka to overcome brilliantly conceptual and technical barriers in 2006 and generate induced pluripotent stem cells (iPSCs) from mouse fibroblasts by overexpressing defined combinations of ESC-enriched transcription factors. Here, we discuss some important implications of human iPSCs for biology and medicine and also point to possible future directions.

  19. Thermal Inkjet Printing in Tissue Engineering and Regenerative Medicine

    PubMed Central

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

    2013-01-01

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

  20. [Regenerative medicine: orthopaedical applications and medico legal questions].

    PubMed

    Ricci, S; Ricci, O; Tucci, C E; Massoni, F; Sarra, M V; Ricci, S

    2012-01-01

    Over the last decades, the increase in the global population's mean age has implied a corresponding increase in degenerative disease affecting various anatomical areas and tissues, including bones and cartilages, thus provoking a rising number of disabilities and a wider usage of drugs, mostly anti-inflammatory and cortisone. New developments in technologic and biomedical fields gave birth to new subjects, such as tissue engineering, cell therapy, gene therapy that, by and large, create a knowledge network falling under the concept of Regenerative Medicine. This science is essentially based on the usage of stem cells that can replicate and renovate themselves originating, if adequately stimulated, a number of cell types. Inter alia, in orthopaedic field a particular type of adult stem cells is used, the mesenchymal stem cells (MSCs). If combined with synthetic material produced in laboratories, the usage of these cells has provided inspiration for new study interests; today, it can be applied in various degenerative and post-traumatic pathologies, with great therapeutic benefits for the patient. Actually, many studies write about an improvement in patients' life quality. In this sense appear significant reflections on legal medicine, both in accidents and insurance, of this innovative therapeutic alternative and is hopefully an equally valid process of improvement of regulatory and case law.

  1. Stem Cell Banking for Regenerative and Personalized Medicine

    PubMed Central

    Harris, David T.

    2014-01-01

    Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today’s intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source. PMID:28548060

  2. Thermal inkjet printing in tissue engineering and regenerative medicine.

    PubMed

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

    2012-08-01

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

  3. Induced pluripotent stem cell technology in regenerative medicine and biology.

    PubMed

    Pei, Duanqing; Xu, Jianyong; Zhuang, Qiang; Tse, Hung-Fat; Esteban, Miguel A

    2010-01-01

    The potential of human embryonic stem cells (ESCs) for regenerative medicine is unquestionable, but practical and ethical considerations have hampered clinical application and research. In an attempt to overcome these issues, the conversion of somatic cells into pluripotent stem cells similar to ESCs, commonly termed nuclear reprogramming, has been a top objective of contemporary biology. More than 40 years ago, King, Briggs, and Gurdon pioneered somatic cell nuclear reprogramming in frogs, and in 1981 Evans successfully isolated mouse ESCs. In 1997 Wilmut and collaborators produced the first cloned mammal using nuclear transfer, and then Thomson obtained human ESCs from in vitro fertilized blastocysts in 1998. Over the last 2 decades we have also seen remarkable findings regarding how ESC behavior is controlled, the importance of which should not be underestimated. This knowledge allowed the laboratory of Shinya Yamanaka to overcome brilliantly conceptual and technical barriers in 2006 and generate induced pluripotent stem cells (iPSCs) from mouse fibroblasts by overexpressing defined combinations of ESC-enriched transcription factors. Here, we discuss some important implications of human iPSCs for biology and medicine and also point to possible future directions.

  4. Cartilage repair: past and future – lessons for regenerative medicine

    PubMed Central

    Van Osch, Gerjo J V M; Brittberg, Mats; Dennis, James E; Bastiaansen-Jenniskens, Yvonne M; Erben, Reinhold G; Konttinen, Yrjö T; Luyten, Frank P

    2009-01-01

    Abstract Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular studies using new technologies such as cell tracking, gene arrays and proteomics have provided more insight in the cell biology and mechanisms of joint surface regeneration. Besides articular cartilage, cartilage of other anatomical locations as well as progenitor cells are now considered as alternative cell sources. Growth Factor research has revealed some information on optimal conditions to support cartilage repair. Thus, there is hope for improvement. In order to obtain more robust and reproducible results, more detailed information is needed on many aspects including the fate of the cells, choice of cell type and culture parameters. As for the clinical aspects, it becomes clear that careful selection of patient groups is an important input parameter that should be optimized for each application. In addition, the study outcome parameters should be improved. Although reduced pain and improved function are, from the patient's perspective, the most important outcomes, there is a need for more structure/tissue-related outcome measures. Ideally, criteria and/or markers to identify patients at risk and responders to treatment are the ultimate goal for these more sophisticated regenerative approaches in joint surface repair in particular, and regenerative medicine in general. PMID:19453519

  5. Scaffold characterization using NLO multimodal microscopy in metrology for regenerative medicine

    NASA Astrophysics Data System (ADS)

    Mortati, Leonardo; Divieto, Carla; Boffitto, Monica; Sartori, Susanna; Ciardelli, Gianluca; Sassi, Maria Paola

    2013-09-01

    Metrology in regenerative medicine aims to develop traceable measurement technologies for characterizing cellular and macromolecule behaviour in regenerative medicine products and processes. One key component in regenerative medicine is using three-dimensional porous scaffolds to guide cells during the regeneration process. The regeneration of specific tissues guided by tissue analogous substrates is dependent on diverse scaffold architectural properties that can be derived quantitatively from scaffolds images. This paper discuss the results obtained with the multimodal NLO microscope recently realized in our laboratory in characterizing 3D tissue engineered (TE) scaffolds colonized from human Mesenchimal stem cells (hMSC), focusing on the study of the three-dimensional metrological parameters.

  6. Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine

    NASA Astrophysics Data System (ADS)

    Chien, Karen B.

    Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood

  7. Regenerative Medicine Approaches for Age-Related Muscle Loss and Sarcopenia: A Mini-Review.

    PubMed

    Naranjo, Juan Diego; Dziki, Jenna L; Badylak, Stephen F

    2017-08-17

    Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein. © 2017 S. Karger AG, Basel.

  8. Growing bioengineered teeth from single cells: potential for dental regenerative medicine.

    PubMed

    Ikeda, Etsuko; Tsuji, Takashi

    2008-06-01

    The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs that can replace organs lost or damaged due to disease, injury or aging. Dental regenerative medicine has made the most progress and is the most useful model for the consideration of strategies in future organ replacement therapies. This review describes strategies that have been pursued to date and experiments currently being conducted to bioengineer teeth in anticipation of the production of fully functional organs. To realize the practical application of 'bioengineered tooth' transplantation therapy, four major hurdles must be overcome. The present status of the hurdles to this therapy are described and discussed in this review. The bioengineering techniques developed for tooth regeneration will in the future make substantial contributions to the ability to grow primordial organs in vitro and also to grow fully functioning organs, such as the liver, kidney and heart.

  9. Tissue engineering and regenerative medicine: history, progress, and challenges.

    PubMed

    Berthiaume, François; Maguire, Timothy J; Yarmush, Martin L

    2011-01-01

    The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.

  10. Stem cells from amniotic fluid--Potential for regenerative medicine.

    PubMed

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-02-01

    Regenerative medicine has recently been established as an emerging field focussing on repair, replacement or regeneration of cells, tissues and whole organs. The significant recent advances in the field have intensified the search for novel sources of stem cells with potential for therapy. Recently, researchers have identified the amniotic fluid as an untapped source of stem cells that are multipotent, possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. Stem cells from the amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, which make them an ideal candidate for tissue engineering applications. In addition, their ability to engraft in injured organs and modulate immune and repair responses of host tissues suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases affecting major tissues/organs. This review summarises the evidence on amniotic fluid cells over the past 15 years and explores the potential therapeutic applications of amniotic fluid stem cells and amniotic fluid mesenchymal stem cells.

  11. Harnessing the potential of lung stem cells for regenerative medicine.

    PubMed

    McQualter, Jonathan L; Anthony, Desiree; Bozinovski, Steven; Prêle, Cecilia M; Laurent, Geoffrey J

    2014-11-01

    In response to recurrent exposure to environmental insults such as allergens, pollution, irritants, smoke and viral/bacterial infection, the epithelium of the lung is continually damaged. Homeostasis of the lung requires a balance between immune regulation and promotion of tissue regeneration, which requires the co-ordinated proliferation and differentiation of stem and progenitor cells. In this review we reflect on the current understanding of lung epithelial stem and progenitor cells and advocate a model hierarchy in which self-renewing multipotent lung epithelial stem cells give rise to lineage restricted progenitor cells that repopulate airway and alveolar epithelial cell lineages during homeostasis and repair. We also discuss the role of mesenchymal progenitor cells in maintaining the structural integrity of the lung and propose a model in which mesenchymal cells act as the quintessential architects of lung regeneration by providing molecular signals, such as FGF-10, to regulate the fate and specificity of epithelial stem and progenitor cells. Moreover, we discuss the current status and future prospects for translating lung stem cell therapies to the clinic to replace, repair, or regenerate diseased lung tissue. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.

  12. Adipose tissue-derived stem cells in neural regenerative medicine.

    PubMed

    Yeh, Da-Chuan; Chan, Tzu-Min; Harn, Horng-Jyh; Chiou, Tzyy-Wen; Chen, Hsin-Shui; Lin, Zung-Sheng; Lin, Shinn-Zong

    2015-01-01

    Adipose tissue-derived stem cells (ADSCs) have two essential characteristics with regard to regenerative medicine: the convenient and efficient generation of large numbers of multipotent cells and in vitro proliferation without a loss of stemness. The implementation of clinical trials has prompted widespread concern regarding safety issues and has shifted research toward the therapeutic efficacy of stem cells in dealing with neural degeneration in cases such as stroke, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, cavernous nerve injury, and traumatic brain injury. Most existing studies have reported that cell therapies may be able to replenish lost cells and promote neuronal regeneration, protect neuronal survival, and play a role in overcoming permanent paralysis and loss of sensation and the recovery of neurological function. The mechanisms involved in determining therapeutic capacity remain largely unknown; however, this concept can still be classified in a methodical manner by citing current evidence. Possible mechanisms include the following: 1) the promotion of angiogenesis, 2) the induction of neuronal differentiation and neurogenesis, 3) reductions in reactive gliosis, 4) the inhibition of apoptosis, 5) the expression of neurotrophic factors, 6) immunomodulatory function, and 7) facilitating neuronal integration. In this study, several human clinical trials using ADSCs for neuronal disorders were investigated. It is suggested that ADSCs are one of the choices among various stem cells for translating into clinical application in the near future.

  13. Computational immuno-biology for organ transplantation and regenerative medicine.

    PubMed

    Vásquez-Montoya, Gustavo A; Danobeitia, Juan S; Fernández, Luis A; Hernández-Ortiz, Juan P

    2016-10-01

    Organ transplantation and regenerative medicine are adopted platforms that provide replacement tissues and organs from natural or engineered sources. Acceptance, tolerance and rejection depend greatly on the proper control of the immune response against graft antigens, motivating the development of immunological and genetical therapies that prevent organ failure. They rely on a complete, or partial, understanding of the immune system. Ultimately, they are innovative technologies that ensure permanent graft tolerance and indefinite graft survival through the modulation of the immune system. Computational immunology has arisen as a tool towards a mechanistic understanding of the biological and physicochemical processes surrounding an immune response. It comprehends theoretical and computational frameworks that simulate immuno-biological systems. The challenge is centered on the multi-scale character of the immune system that spans from atomistic scales, during peptide-epitope and protein interactions, to macroscopic scales, for lymph transport and organ-organ reactions. In this paper, we discuss, from an engineering perspective, the biological processes that are involved during the immune response of organ transplantation. Previous computational efforts, including their characteristics and visible limitations, are described. Finally, future perspectives and challenges are listed to motivate further developments.

  14. Dedifferentiated fat cells: A cell source for regenerative medicine.

    PubMed

    Jumabay, Medet; Boström, Kristina I

    2015-11-26

    The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipid-free multipotent cells, referred to as dedifferentiated fat (DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.

  15. Dedifferentiated fat cells: A cell source for regenerative medicine

    PubMed Central

    Jumabay, Medet; Boström, Kristina I

    2015-01-01

    The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipid-free multipotent cells, referred to as dedifferentiated fat (DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration. PMID:26640620

  16. Potency of Fish Collagen as a Scaffold for Regenerative Medicine

    PubMed Central

    Yamamoto, Kohei; Yanagiguchi, Kajiro

    2014-01-01

    Cells, growth factors, and scaffold are the crucial factors for tissue engineering. Recently, scaffolds consisting of natural polymers, such as collagen and gelatin, bioabsorbable synthetic polymers, such as polylactic acid and polyglycolic acid, and inorganic materials, such as hydroxyapatite, as well as composite materials have been rapidly developed. In particular, collagen is the most promising material for tissue engineering due to its biocompatibility and biodegradability. Collagen contains specific cell adhesion domains, including the arginine-glycine-aspartic acid (RGD) motif. After the integrin receptor on the cell surface binds to the RGD motif on the collagen molecule, cell adhesion is actively induced. This interaction contributes to the promotion of cell growth and differentiation and the regulation of various cell functions. However, it is difficult to use a pure collagen scaffold as a tissue engineering material due to its low mechanical strength. In order to make up for this disadvantage, collagen scaffolds are often modified using a cross-linker, such as gamma irradiation and carbodiimide. Taking into account the possibility of zoonosis, a variety of recent reports have been documented using fish collagen scaffolds. We herein review the potency of fish collagen scaffolds as well as associated problems to be addressed for use in regenerative medicine. PMID:24982861

  17. Regenerative medicine for the treatment of heart disease.

    PubMed

    Hansson, E M; Lendahl, U

    2013-03-01

    Heart failure is a major cause of mortality worldwide with a steady increase in prevalence. There is currently no available cure beyond orthotopic heart transplantation, which for a number of reasons is an option only for a small fraction of all patients. Considerable hope has therefore been placed on the possibility of treating a failing heart by replacing lost cardiomyocytes, either through transplantation of various types of stem cells or by boosting endogenous regenerative mechanisms in the heart. Here, we review the current status of stem and progenitor cell-based therapies for heart disease. We discuss the pros and cons of different stem and progenitor cell types that can be considered for transplantation and describe recent advances in the understanding of how cardiomyocytes normally differentiate and how these cells can be generated from more immature cells ex vivo. Finally, we consider the possibility of activation of endogenous stem and progenitor cells to treat heart failure. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  18. Tissue Engineering and Regenerative Medicine 2015: A Year in Review

    PubMed Central

    Wobma, Holly

    2016-01-01

    This may be the most exciting time ever for the field of tissue engineering and regenerative medicine (TERM). After decades of progress, it has matured, integrated, and diversified into entirely new areas, and it is starting to make the pivotal shift toward translation. The most exciting science and applications continue to emerge at the boundaries of disciplines, through increasingly effective interactions between stem cell biologists, bioengineers, clinicians, and the commercial sector. In this “Year in Review,” we highlight some of the major advances reported over the last year (Summer 2014–Fall 2015). Using a methodology similar to that established in previous years, we identified four areas that generated major progress in the field: (i) pluripotent stem cells, (ii) microtissue platforms for drug testing and disease modeling, (iii) tissue models of cancer, and (iv) whole organ engineering. For each area, we used some of the most impactful articles to illustrate the important concepts and results that advanced the state of the art of TERM. We conclude with reflections on emerging areas and perspectives for future development in the field. PMID:26714410

  19. Lacrimal gland development: From signaling interactions to regenerative medicine.

    PubMed

    Garg, Ankur; Zhang, Xin

    2017-07-14

    The lacrimal gland plays a pivotal role in keeping the ocular surface lubricated, and protecting it from environmental exposure and insult. Dysfunction of the lacrimal gland results in deficiency of the aqueous component of the tear film, which can cause dryness of the ocular surface, also known as the aqueous-deficient dry eye disease. Left untreated, this disease can lead to significant morbidity, including frequent eye infections, corneal ulcerations, and vision loss. Current therapies do not treat the underlying deficiency of the lacrimal gland, but merely provide symptomatic relief. To develop more sustainable and physiological therapies, such as in vivo lacrimal gland regeneration or bioengineered lacrimal gland implants, a thorough understanding of lacrimal gland development at the molecular level is of paramount importance. Based on the structural and functional similarities between rodent and human eye development, extensive studies have been undertaken to investigate the signaling and transcriptional mechanisms of lacrimal gland development using mouse as a model system. In this review, we describe the current understanding of the extrinsic signaling interactions and the intrinsic transcriptional network governing lacrimal gland morphogenesis, as well as recent advances in the field of regenerative medicine aimed at treating dry eye disease. Developmental Dynamics, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Porous tantalum and tantalum oxide nanoparticles for regenerative medicine.

    PubMed

    Mohandas, Gokhuldass; Oskolkov, Nikita; McMahon, Michael T; Walczak, Piotr; Janowski, Miroslaw

    2014-01-01

    For centuries, inflammatory/foreign body reactions have plagued the attempts of clinicians to use metals for tissue and bone reconstructions. Since corrosion contributes to the rejection of metal by the body, an extremely bioinert metal - tantalum - has been successfully used in medicine. The outstanding biocompatibility and flexibility of tantalum established the basis for a growing cadre of clinical applications. One important application which benefited from the introduction of powder (particle) metallurgy is use of tantalum as bone implants. Porous materials have re-shaped the landscape of bone implants, as they allow for bone ingrowth and biological fixation, and eliminate implant loosening and related treatment failures. The unique bone-mimicking properties of porous tantalum enabled the use of tantalum as a material for bulk implants, and not only for coatings, as is the case with other porous metals. Moreover, porous tantalum also facilitates the ingrowth of soft tissue, including the formation of blood vessels that were found to assemble on the surface and within the structure of the porous tantalum. Also, since tantalum is strongly radiopaque due its high atomic number, this property is widely employed for marking in orthopedics and in endovascular medical devices. Another important development was the production of nanoparticles based on tantalum. These particles have been shown to be superior to iodinated contrast agents for blood pool imaging applications due to their longer circulation time. Their properties are similar to gold nanoparticles, but are far more cost-effective, and thus, well-positioned to replace gold in regenerative medicine for labeling and tracking of cell grafts through x-ray-based imaging. However, the amount of tantalum nanoparticles that can be taken up by stem cells is not enough to make individual cells visible in x-ray images. Thus, alternative strategies are needed, such as hydrogel or nanofiber scaffolds, which can be loaded

  1. Dental pulp stem cells: function, isolation and applications in regenerative medicine.

    PubMed

    Tatullo, Marco; Marrelli, Massimo; Shakesheff, Kevin M; White, Lisa J

    2015-11-01

    Dental pulp stem cells (DPSCs) are a promising source of cells for numerous and varied regenerative medicine applications. Their natural function in the production of odontoblasts to create reparative dentin support applications in dentistry in the regeneration of tooth structures. However, they are also being investigated for the repair of tissues outside of the tooth. The ease of isolation of DPSCs from discarded or removed teeth offers a promising source of autologous cells, and their similarities with bone marrow stromal cells (BMSCs) suggest applications in musculoskeletal regenerative medicine. DPSCs are derived from the neural crest and, therefore, have a different developmental origin to BMSCs. These differences from BMSCs in origin and phenotype are being exploited in neurological and other applications. This review briefly highlights the source and functions of DPSCs and then focuses on in vivo applications across the breadth of regenerative medicine. © 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

  2. CCRM: cultivating a culture of cooperation to advance the global regenerative medicine industry.

    PubMed

    Evans, Alanna; Johnson, Stacey

    2016-12-01

    Launched in June 2011, CCRM is a unique, Canadian, not-for-profit group that is solely focused on developing and commercializing regenerative medicine, cell and gene therapy technologies. Its mission is to generate sustainable health and economic benefits through global collaborations, and its vision is to be the preferred destination for the best people and companies, technologies, clinical trials and investments in cell and gene therapies, and regenerative medicine.

  3. Microfabricated Modular Scale-Down Device for Regenerative Medicine Process Development

    PubMed Central

    Reichen, Marcel; Macown, Rhys J.; Jaccard, Nicolas; Super, Alexandre; Ruban, Ludmila; Griffin, Lewis D.; Veraitch, Farlan S.; Szita, Nicolas

    2012-01-01

    The capacity of milli and micro litre bioreactors to accelerate process development has been successfully demonstrated in traditional biotechnology. However, for regenerative medicine present smaller scale culture methods cannot cope with the wide range of processing variables that need to be evaluated. Existing microfabricated culture devices, which could test different culture variables with a minimum amount of resources (e.g. expensive culture medium), are typically not designed with process development in mind. We present a novel, autoclavable, and microfabricated scale-down device designed for regenerative medicine process development. The microfabricated device contains a re-sealable culture chamber that facilitates use of standard culture protocols, creating a link with traditional small-scale culture devices for validation and scale-up studies. Further, the modular design can easily accommodate investigation of different culture substrate/extra-cellular matrix combinations. Inactivated mouse embryonic fibroblasts (iMEF) and human embryonic stem cell (hESC) colonies were successfully seeded on gelatine-coated tissue culture polystyrene (TC-PS) using standard static seeding protocols. The microfluidic chip included in the device offers precise and accurate control over the culture medium flow rate and resulting shear stresses in the device. Cells were cultured for two days with media perfused at 300 µl.h−1 resulting in a modelled shear stress of 1.1×10−4 Pa. Following perfusion, hESC colonies stained positively for different pluripotency markers and retained an undifferentiated morphology. An image processing algorithm was developed which permits quantification of co-cultured colony-forming cells from phase contrast microscope images. hESC colony sizes were quantified against the background of the feeder cells (iMEF) in less than 45 seconds for high-resolution images, which will permit real-time monitoring of culture progress in future experiments. The

  4. Obstacles in Renal Regenerative Medicine: Metabolic and Epigenetic Parallels Between Cellular Reprogramming and Kidney Cancer Oncogenesis.

    PubMed

    Lichner, Zsuzsanna; Mac-Way, Fabrice; Yousef, George M

    2017-08-25

    Regenerative medicine has recently presented a revolutionary solution to end-stage kidney disease. Reprogramming patients' own cells generates induced pluripotent stem cells that are subsequently differentiated to "kidney organoid," a structure that is anatomically and functionally similar to the kidney. This approach holds the promise of a transplantable, immunocompetent, and functional kidney that could be produced in vitro. However, caution must be taken due to the molecular-level similarities between induced pluripotent stem cells and renal cell carcinomas. As such, if cell reprogramming is not tightly controlled, it can lead to carcinogenic changes. Based on recent next-generation sequencing results and other supporting data, we identified three major molecular attributes of renal cell carcinoma: metabolic alterations, epigenetic changes, and miRNA-based alterations. Strikingly, these variations are mirrored in induced pluripotent stem cells, which are the main cell source of renal regenerative medicine. Our objective was to discuss the shared metabolic, epigenetic and miRNA-regulated characteristics and to abridge their significance in renal regenerative medicine. English-language literature was retrieved through PubMed. Authors collected the published evidence and evaluated the content based on independent literature findings. Articles were filtered to include only highly relevant, recent publications that presented reproducible results by authorities of the field. The kidney represents a unique metabolic environment that could be hijacked by induced pluripotent stem cells or by partially differentiated cells for oncogenic transformation. Future differentiation protocols must produce kidney organoids that are fully engaged in filtration function. A new technology can produce mini-kidneys or kidney organoids. This review discusses some of the challenges this technology has to face, including its high oncogenic potential. Understanding these similarities will

  5. Printing of Three-Dimensional Tissue Analogs for Regenerative Medicine.

    PubMed

    Lee, Vivian K; Dai, Guohao

    2017-01-01

    Three-dimensional (3-D) cell printing, which can accurately deposit cells, biomaterial scaffolds and growth factors in precisely defined spatial patterns to form biomimetic tissue structures, has emerged as a powerful enabling technology to create live tissue and organ structures for drug discovery and tissue engineering applications. Unlike traditional 3-D printing that uses metals, plastics and polymers as the printing materials, cell printing has to be compatible with living cells and biological matrix. It is also required that the printing process preserves the biological functions of the cells and extracellular matrix, and to mimic the cell-matrix architectures and mechanical properties of the native tissues. Therefore, there are significant challenges in order to translate the technologies of traditional 3-D printing to cell printing, and ultimately achieve functional outcomes in the printed tissues. So it is essential to develop new technologies specially designed for cell printing and in-depth basic research in the bioprinted tissues, such as developing novel biomaterials specifically for cell printing applications, understanding the complex cell-matrix remodeling for the desired mechanical properties and functional outcomes, establishing proper vascular perfusion in bioprinted tissues, etc. In recent years, many exciting research progresses have been made in the 3-D cell printing technology and its application in engineering live tissue constructs. This review paper summarized the current development in 3-D cell printing technologies; focus on the outcomes of the live printed tissues and their potential applications in drug discovery and regenerative medicine. Current challenges and limitations are highlighted, and future directions of 3-D cell printing technology are also discussed.

  6. Stem Cell and Regenerative Medicine Global Conference (SCRGC) 2016 (August 23-24, 2016 - Gyeonggi-do, Korea).

    PubMed

    Vertès, A

    2016-10-01

    In its third edition, the Stem Cell and Regenerative Medicine Global Conference (SCRGC) organized by the Global Stem Cell & Regenerative Medicine Acceleration Center (GSRAC) was focused on breaking barriers to accelerate the pace of innovation and development of the regenerative medicine industry. GSRAC is both a think tank and a global network of key opinion leaders from the public and the private sectors. GSRAC was commissioned in 2011 by the Ministry of Health and Welfare (MOHW) of Korea. GSRAC's primary mission is to enable and accelerate the delivery of innovative technologies to patients who are affected by currently untreatable diseases. This goal is notably achieved by resolving hurdles in the field of regenerative medicine. With a total of 30 speakers and panelists from 8 different countries and more than 400 attendees from an array of institutions including hospitals, clinics, biotechnology companies, pharmaceutical companies, scientists, as well as policy makers, the 2-day SCRGC highlighted critical challenges and paths to resolving them in policy and regulatory, and industrial-scale manufacturing of gene-based and cell-based therapies, comprising plenary lectures and sessions covering strategic policy, regulatory, reimbursement and business development, and business of manufacturing, and production technologies. Several of these presentations are summarized in this report.

  7. Tissue engineering and regenerative medicine approaches to enhance the functional response to skeletal muscle injury.

    PubMed

    Sicari, Brian M; Dearth, Christopher L; Badylak, Stephen F

    2014-01-01

    The well-recognized ability of skeletal muscle for functional and structural regeneration following injury is severely compromised in degenerative diseases and in volumetric muscle loss. Tissue engineering and regenerative medicine strategies to support muscle reconstruction have typically been cell-centric with approaches that involve the exogenous delivery of cells with myogenic potential. These strategies have been limited by poor cell viability and engraftment into host tissue. Alternative approaches have involved the use of biomaterial scaffolds as substrates or delivery vehicles for exogenous myogenic progenitor cells. Acellular biomaterial scaffolds composed of mammalian extracellular matrix (ECM) have also been used as an inductive niche to promote the recruitment and differentiation of endogenous myogenic progenitor cells. An acellular approach, which activates or utilizes endogenous cell sources, obviates the need for exogenous cell administration and provides an advantage for clinical translation. The present review examines the state of tissue engineering and regenerative medicine therapies directed at augmenting the skeletal muscle response to injury and presents the pros and cons of each with respect to clinical translation.

  8. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    NASA Astrophysics Data System (ADS)

    Sharma, Gulshan B.; Robertson, Douglas D.

    2013-07-01

    specimen. Low predicted bone density was lower than actual specimen. Differences were probably due to applied muscle and joint reaction loads, boundary conditions, and values of constants used. Work is underway to study this. Nonetheless, the results demonstrate three dimensional bone remodeling simulation validity and potential. Such adaptive predictions take physiological bone remodeling simulations one step closer to reality. Computational analyses are needed that integrate biological remodeling rules and predict how bone will respond over time. We expect the combination of computational static stress analyses together with adaptive bone remodeling simulations to become effective tools for regenerative medicine research.

  9. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    SciTech Connect

    Sharma, Gulshan B.; Robertson, Douglas D.

    2013-07-01

    actual specimen. Low predicted bone density was lower than actual specimen. Differences were probably due to applied muscle and joint reaction loads, boundary conditions, and values of constants used. Work is underway to study this. Nonetheless, the results demonstrate three dimensional bone remodeling simulation validity and potential. Such adaptive predictions take physiological bone remodeling simulations one step closer to reality. Computational analyses are needed that integrate biological remodeling rules and predict how bone will respond over time. We expect the combination of computational static stress analyses together with adaptive bone remodeling simulations to become effective tools for regenerative medicine research.

  10. RGTA(®)-based matrix therapy - A new branch of regenerative medicine in locomotion.

    PubMed

    Barritault, Denis; Desgranges, Pascal; Meddahi-Pellé, Anne; Denoix, Jean-Marie; Saffar, Jean-Louis

    2016-09-20

    Matrix therapy is an innovative, minimally invasive approach in the field of regenerative medicine, that aims to promote tissue regeneration by reconstructing the cellular microenvironment following tissue injury. This approach has significant therapeutic potential in the treatment of pathologies characterized by tissue inflammation and damage, or following injury, conditions which can be incapacitating and cost-consuming. Heparan sulfate mimics, termed ReGeneraTing Agents (RGTA(®)s) have emerged as a unifying approach to treat these diverse pathologies. Today, skin and corneal healing topical products have already been used in clinics, demonstrating a proof of concept in humans. In this review, we present key evidence that RGTA(®)s regenerate damaged tissue in bone, muscle, tendon and nerve, with astonishing results. In animal models of bone surgical defects and inflammatory bone loss, RGTA(®) induced healing of injured bones by controlling inflammation and bone resorption, and stimulated bone formation by coordinating vascularization, recruitment and differentiation of competent cells from specific niches, restoring tissue quality to that of uninjured tissue, evoking true regeneration. In models of muscle injury, RGTA(®) had marked effects on healing speed and quality, evidenced by increased muscle fiber density, maturation, vascularization and reduced fibrosis, more mature motor endplates and functional recovery. Applications merging RGTA(®)-based matrix therapy and cell therapy, combining Extra-Cellular Matrix reconstruction with cells required for optimal tissue repair show significant promise. Hence restoration of the proper microenvironment is a new paradigm in regenerative medicine. Harnessing the potential of RGTA(®) in this brave, new vision of regenerative therapy will therefore be the focus of future studies.

  11. Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine

    PubMed Central

    Rodríguez-Vázquez, Martin; Vega-Ruiz, Brenda; Ramos-Zúñiga, Rodrigo; Saldaña-Koppel, Daniel Alexander; Quiñones-Olvera, Luis Fernando

    2015-01-01

    Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer. PMID:26504833

  12. Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine.

    PubMed

    Rodríguez-Vázquez, Martin; Vega-Ruiz, Brenda; Ramos-Zúñiga, Rodrigo; Saldaña-Koppel, Daniel Alexander; Quiñones-Olvera, Luis Fernando

    2015-01-01

    Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer.

  13. Application of 3D biomimetic models in drug delivery and regenerative medicine.

    PubMed

    Xu, Yufan; Wang, Xiaohong

    2015-01-01

    Regenerative medicine holds much promise in assisting patients to recover from injured or lost tissues and organs through organism reconstruction. Three-dimensional (3D) biomimetic models via various approaches can be used by pharmaceutical industry for controlled drug delivery. With proper biomaterials and engineering technologies, drugs can be released in a rate-manipulated manner towards targeted regions with spatial and temporal effects. Much of the success is a result of a combination of growth factors, stem cells, biomaterials, nanotechnologies, electrospinning and 3D printing techniques mimicking in vivo angiogenesis, histogenesis and tumorigenesis processes. This interdisciplinary field on biomimetic drug delivery and regenerative medicine has already opened up a new avenue for medical progress and reformation. This article presents a comprehensive review of the 3D biomimetic models in the pertinent fields of tissue and organ manufacturing, cell-material mutual interactions, bioactive agent carrier systems and anti-cancer drug delivery methods. Particularly, the potential trends and challenges of tissue and organ manufacturing are discussed from different perspectives.

  14. Integration of drug, protein, and gene delivery systems with regenerative medicine.

    PubMed

    Lorden, Elizabeth R; Levinson, Howard M; Leong, Kam W

    2015-04-01

    Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g., hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and microparticle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein, and gene delivery in the context of regenerative medicine. Next, we will present case examples of how delivery technologies are being applied to promote angiogenesis in nonhealing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench to bedside for the clinical translation of these novel therapeutics.

  15. Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine.

    PubMed

    Gomes, Kátia Maria Sampaio; Costa, Ismael Cabral; Santos, Jeniffer Farias Dos; Dourado, Paulo Magno Martins; Forni, Maria Fernanda; Ferreira, Julio Cesar Batista

    2017-02-01

    Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.

  16. Integration of Drug, Protein, and Gene Delivery Systems with Regenerative Medicine

    PubMed Central

    Lorden, Elizabeth R.; Levinson, Howard M.; Leong, Kam W.

    2013-01-01

    Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g. hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and micro-particle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein and gene delivery in the context of regenerative medicine. Next we will present case examples of how delivery technologies are being applied to promote angiogenesis in non-healing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench-to-bedside for the clinical translation of these novel therapeutics. PMID:25787742

  17. Regenerative medicine for diseases of the head and neck: principles of in vivo regeneration.

    PubMed

    Löwenheim, H

    2003-09-01

    The application of endogenous regeneration in regenerative medicine is based on the concept of inducing regeneration of damaged or lost tissues from residual tissues in situ. Therefore, endogenous regeneration is also termed in vivo regeneration as opposed to mechanisms of ex vivo regeneration which are applied, for example, in the field of tissue engineering. The basic science foundation for mechanisms of endogenous regeneration is provided by the field of regenerative biology. The ambitious vision for the application of endogenous regeneration in regenerative medicine is stimulated by investigations in the model organisms of regenerative biology, most notably hydra, planarians and urodeles. These model organisms demonstrate remarkable regenerative capabilities, which appear to be conserved over large phylogenetical stretches with convincing evidence for a homologue origin of an endogenous regenerative capability. Although the elucidation of the molecular and cellular mechanisms of these endogenous regenerative phenomena is still in its beginning, there are indications that these processes have potential to become useful for human benefit. Such indications also exist for particular applications in diseases of the head and neck region. As such epimorphic regeneration without blastema formation may be relevant to regeneration of sensorineural epithelia of the inner ear or the olphactory epithelium. Complex tissue lesions of the head and neck as they occur after trauma or tumor resections may be approached on the basis of relevant mechanisms in epimorphic regeneration with blastema formation.

  18. Tissue engineering and regenerative medicine in applied research: a year in review of 2014.

    PubMed

    Lin, Xunxun; Huang, Jia; Shi, Yuan; Liu, Wei

    2015-04-01

    Tissue engineering and regenerative medicine (TERM) remains to be one of the fastest growing fields, which covers a wide scope of topics of both basic and applied biological researches. This overview article summarized the advancements in applied researches of TERM area, including stem cell-mediated tissue regeneration, material science, and TERM clinical trial. These achievements demonstrated the great potential of clinical regenerative therapy of tissue/organ disease or defect through stem cells and tissue engineering approaches.

  19. Phage Display Technology in Biomaterials Engineering: Progress and Opportunities for Applications in Regenerative Medicine.

    PubMed

    Martins, Ivone M; Reis, Rui L; Azevedo, Helena S

    2016-11-18

    The field of regenerative medicine has been gaining momentum steadily over the past few years. The emphasis in regenerative medicine is to use various in vitro and in vivo approaches that leverage the intrinsic healing mechanisms of the body to treat patients with disabling injuries and chronic diseases such as diabetes, osteoarthritis, and degenerative disorders of the cardiovascular and central nervous system. Phage display has been successfully employed to identify peptide ligands for a wide variety of targets, ranging from relatively small molecules (enzymes, cell receptors) to inorganic, organic, and biological (tissues) materials. Over the past two decades, phage display technology has advanced tremendously and has become a powerful tool in the most varied fields of research, including biotechnology, materials science, cell biology, pharmacology, and diagnostics. The growing interest in and success of phage display libraries is largely due to its incredible versatility and practical use. This review discusses the potential of phage display technology in biomaterials engineering for applications in regenerative medicine.

  20. Generation of thyroid follicular cells from pluripotent stem cells: potential for regenerative medicine.

    PubMed

    Sewell, Will; Lin, Reigh-Yi

    2014-01-01

    Nearly 12% of the population in the United States will be afflicted with a thyroid related disorder during their lifetime. Common treatment approaches are tailored to the specific disorder and include surgery, radioactive iodine ablation, antithyroid drugs, thyroid hormone replacement, external beam radiation, and chemotherapy. Regenerative medicine endeavors to combat disease by replacing or regenerating damaged, diseased, or dysfunctional body parts. A series of achievements in pluripotent stem cell research have transformed regenerative medicine in many ways by demonstrating "repair" of a number of body parts in mice, of which, the thyroid has now been inducted into this special group. Seminal work in pluripotent cells, namely embryonic stem cells and induced pluripotent stem cells, have made possible their path to becoming key tools and biological building blocks for cell-based regenerative medicine to combat the gamut of human diseases, including those affecting the thyroid.

  1. Generation of Thyroid Follicular Cells from Pluripotent Stem Cells: Potential for Regenerative Medicine

    PubMed Central

    Sewell, Will; Lin, Reigh-Yi

    2014-01-01

    Nearly 12% of the population in the United States will be afflicted with a thyroid related disorder during their lifetime. Common treatment approaches are tailored to the specific disorder and include surgery, radioactive iodine ablation, antithyroid drugs, thyroid hormone replacement, external beam radiation, and chemotherapy. Regenerative medicine endeavors to combat disease by replacing or regenerating damaged, diseased, or dysfunctional body parts. A series of achievements in pluripotent stem cell research have transformed regenerative medicine in many ways by demonstrating “repair” of a number of body parts in mice, of which, the thyroid has now been inducted into this special group. Seminal work in pluripotent cells, namely embryonic stem cells and induced pluripotent stem cells, have made possible their path to becoming key tools and biological building blocks for cell-based regenerative medicine to combat the gamut of human diseases, including those affecting the thyroid. PMID:24995001

  2. Recent Advances in Biohybrid Materials for Tissue Engineering and Regenerative Medicine

    NASA Astrophysics Data System (ADS)

    Wan, Ying; Li, Xing; Wang, Shenqi

    2016-07-01

    Biohybrid materials play an important role in tissue engineering, artificial organs and regenerative medicine due to their regulation of cell function through specific cell-matrix interactions involving integrins, mostly those of fibroblasts and myofibroblasts, and ligands on the matrix surface, which have become current research focus. In this paper, recent progress of biohybrid materials, mainly including main types of biohybrid materials, rapid prototype (RP) technique for construction of 3D biohybrid materials, was reviewed in detail; moreover, their applications in tissue engineering, artificial organs and regenerative medicine were also reviewed in detail. At last, we address the challenges biohybrid materials may face.

  3. Tissue Engineering and Regenerative Medicine: The Promise, the Challenges, the Future.

    PubMed

    Mertz, Leslie

    2017-01-01

    Medical researchers increasingly regard tissue engineering and regenerative medicine as potential game changers when it comes to repairing damage from disease or injury and restoring function. To understand the progress made and challenges ahead for this combined field, IEEE Pulse sought out two experts: David F. Williams, former global president (2012-2015) of the Tissue Engineering and Regenerative Medicine International Society, and Roderic I. Pettigrew, founding director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH) [1].

  4. A Murine Model of Volumetric Muscle Loss and a Regenerative Medicine Approach for Tissue Replacement

    PubMed Central

    Sicari, Brian M.; Agrawal, Vineet; Siu, Bernard F.; Medberry, Christopher J.; Dearth, Christopher L.; Turner, Neill J.

    2012-01-01

    Volumetric muscle loss (VML) resulting from traumatic accidents, tumor ablation, or degenerative disease is associated with limited treatment options and high morbidity. The lack of a reliable and reproducible animal model of VML has hindered the development of effective therapeutic strategies. The present study describes a critical-sized excisional defect within the mouse quadriceps muscle that results in an irrecoverable volumetric defect. This model of VML was used to evaluate the efficacy of a surgically placed inductive biologic scaffold material composed of porcine small intestinal submucosa–extracellular matrix (SIS-ECM). The targeted placement of an SIS-ECM scaffold within the defect was associated with constructive tissue remodeling including the formation of site-appropriate skeletal muscle tissue. The present study provides a reproducible animal model with which to study VML and shows the therapeutic potential of a bioscaffold-based regenerative medicine approach to VML. PMID:22906411

  5. Human dental pulp stem cell behavior using natural nanotolith/bacterial cellulose scaffolds for regenerative medicine.

    PubMed

    Olyveira, Gabriel Molina; Acasigua, Gerson Arisoly Xavier; Costa, Ligia Maria Manzine; Scher, Cristiane Regina; Xavier Filho, Lauro; Pranke, Patricia Helena Lucas; Basmaji, Pierre

    2013-08-01

    Adhesion and Viability study with human dental pulp stem cell using natural nanotolith/bacterial cellulose scaffolds for regenerative medicine are presented at first time in this work. Nanotolith, are osteoinductors, i.e., they stimulate bone regeneration, enabling higher cells migration for bone tissue regeneration formation. This is mainly because nanotoliths are rich minerals present in the internal ear of bony fish. In addition, are part of a system which acts as a depth sensor and balance, acting as a sound vibrations detector and considered essential for the bone mineralization process, as in hydroxiapatites. Nanotoliths influence in bacterial cellulose was analyzed using transmission infrared spectroscopy (FTIR). Results shows that fermentation process and nanotoliths agglomeration decrease initial human dental pulp stem cell adhesion however tested bionanocomposite behavior has cell viability increase over time.

  6. Reproductive biology, stem cells biotechnology and regenerative medicine: a 1-day national symposium held at Shahid Sadoughi University of Medical Sciences

    PubMed Central

    Akyash, Fatemeh; Tahajjodi, Somayyeh Sadat; Sadeghian-Nodoushan, Fatemeh; Aflatoonian, Abbas; Abdoli, Ali-Mohammad; Nikukar, Habib; Aflatoonian, Behrouz

    2016-01-01

    This paper summarizes the proceedings of a 1 day national symposium entitled “Reproductive biology, stem cells biotechnology and regenerative medicine” held at Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 3rd March 2016. Here, we collected the papers that presented and discussed at this meeting by specialists that currently researched about the overlaps of the fields of reproductive biology and stem cells and their applications in regenerative medicine.

  7. In silico modeling of structural and porosity properties of additive manufactured implants for regenerative medicine.

    PubMed

    Brünler, Ronny; Aibibu, Dilbar; Wöltje, Michael; Anthofer, Anna-Maria; Cherif, Chokri

    2017-07-01

    Additive manufacturing technologies are a promising technology towards patient-specific implants for applications in regenerative medicine. The Net-Shape-Nonwoven technology is used to manufacture structures from short fibers with interconnected pores and large functional surfaces that are predestined for cell adhesion and growth. The present study reports on a modeling approach with a particular focus on the specific structural properties. The overall porosities and mean pore-sizes of the digital models are simulated according to liquid-displacement porosity in a tool implemented in the modeling software. This allows adjusting the process parameters fiber length and fiber diameter to generate biomimetic structures with pore-sizes adapted to the requirements of the tissue that is to be replaced. Modeling the structural and porosity properties of scaffolds and implants leads to an efficient use of the processed biomaterials as the trial-and-error method is avoided. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Two sides of the same coin: stem cells in cancer and regenerative medicine.

    PubMed

    Ilmer, Matthias; Vykoukal, Jody; Recio Boiles, Alejandro; Coleman, Michael; Alt, Eckhard

    2014-07-01

    Multipotent stromal cells (MSCs) derived from bone marrow, adipose tissue, cord blood, and other origins have recently received much attention as potential therapeutic agents with beneficial immunomodulatory and regenerative properties. In their native tissue environment, however, such cells also appear to have essential functions in building and supporting tumor microenvironments, providing metastatic niches, and maintaining cancer hallmarks. Here, we consider the varied roles of these tissue-resident stroma-associated cells, synthesize recent and emerging discoveries, and discuss the role, potential, and clinical applications of MSCs in cancer and regenerative medicine.-Ilmer, M., Vykoukal, J., Recio Boiles, A., Coleman, M., Alt, E. Two sides of the same coin: stem cells in cancer and regenerative medicine.

  9. Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?

    PubMed Central

    Schäfer, Richard; Spohn, Gabriele; Baer, Patrick C.

    2016-01-01

    Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy. PMID:27721701

  10. Stem cells, growth factors and scaffolds in craniofacial regenerative medicine

    PubMed Central

    Tollemar, Viktor; Collier, Zach J.; Mohammed, Maryam K.; Lee, Michael J.; Ameer, Guillermo A.; Reid, Russell R.

    2015-01-01

    Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects. This strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials, osteoblastic stem cells, as well as osteoinductive growth factors and small molecules. One of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone regeneration. These properties include osteoconduction, osetoinduction, biocompatibility, biodegradability, vascularization, and progenitor cell retention. This review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials. PMID:27239485

  11. Application of Stem Cell Technology in Dental Regenerative Medicine.

    PubMed

    Feng, Ruoxue; Lengner, Chistopher

    2013-07-01

    In this review, we summarize the current literature regarding the isolation and characterization of dental tissue-derived stem cells and address the potential of these cell types for use in regenerative cell transplantation therapy. Looking forward, platforms for the delivery of stem cells via scaffolds and the use of growth factors and cytokines for enhancing dental stem cell self-renewal and differentiation are discussed. We aim to understand the developmental origins of dental tissues in an effort to elucidate the molecular pathways governing the genesis of somatic dental stem cells. The advantages and disadvantages of several dental stem cells are discussed, including the developmental stage and specific locations from which these cells can be purified. In particular, stem cells from human exfoliated deciduous teeth may act as a very practical and easily accessibly reservoir for autologous stem cells and hold the most value in stem cell therapy. Dental pulp stem cells and periodontal ligament stem cells should also be considered for their triple lineage differentiation ability and relative ease of isolation. Further, we address the potentials and limitations of induced pluripotent stem cells as a cell source in dental regenerative. From an economical and a practical standpoint, dental stem cell therapy would be most easily applied in the prevention of periodontal ligament detachment and bone atrophy, as well as in the regeneration of dentin-pulp complex. In contrast, cell-based tooth replacement due to decay or other oral pathology seems, at the current time, an untenable approach.

  12. Viral vector-mediated transgenic cell therapy in regenerative medicine: safety of the process.

    PubMed

    Liu, Yang; Wang, Dong-An

    2015-04-01

    There are safety concerns regarding viral vectors in regenerative medicine research because of adverse experiences in conventional gene therapy with systemic delivery of recombinant virus. Transgenic cell therapy emerges as an attractive strategy, in which the genes of interest are delivered in vitro into isolated cells first; instead of transgene vectors, these transgenic cells are then implanted back to the host. This ex vivo strategy enables the examination of cell viability and phenotype before subsequent transplantation and prevents to the most extent the potential delivery-related hazards caused by exposure of viral components to the host. The transgenic implants are often localized, thus traceable for safety monitoring except those cases involving systemic distribution of transgenic cells. The safety of ex vivo process used in viral vector-mediated transgenic cell therapy for regenerative medicine purpose. Safety concerns related to viral vector delivery can be dispelled in the majority of regenerative medicine applications by transgenic cell therapy. The ex vivo process executes in vitro transfection before subsequent transplantation of transgenic cells so that it avoids the exposure of viral components (particularly capsids or envelops) to the host, while this exposure is inevitable in conventional in vivo gene therapy. Besides, the practice of localized cell implantation and in vitro manipulation also reinforce the safety of transgenic cell therapy. Given the significantly reduced delivery-related hazard, viral vector-mediated transgenic cell therapy can be generally considered as a safe approach for most regenerative medicine applications.

  13. 3D printed PLA-based scaffolds: a versatile tool in regenerative medicine.

    PubMed

    Serra, Tiziano; Mateos-Timoneda, Miguel A; Planell, Josep A; Navarro, Melba

    2013-10-01

    Rapid prototyping (RP), also known as additive manufacturing (AM), has been well received and adopted in the biomedical field. The capacity of this family of techniques to fabricate customized 3D structures with complex geometries and excellent reproducibility has revolutionized implantology and regenerative medicine. In particular, nozzle-based systems allow the fabrication of high-resolution polylactic acid (PLA) structures that are of interest in regenerative medicine. These 3D structures find interesting applications in the regenerative medicine field where promising applications including biodegradable templates for tissue regeneration purposes, 3D in vitro platforms for studying cell response to different scaffolds conditions and for drug screening are considered among others. Scaffolds functionality depends not only on the fabrication technique, but also on the material used to build the 3D structure, the geometry and inner architecture of the structure, and the final surface properties. All being crucial parameters affecting scaffolds success. This Commentary emphasizes the importance of these parameters in scaffolds' fabrication and also draws the attention toward the versatility of these PLA scaffolds as a potential tool in regenerative medicine and other medical fields.

  14. National Institutes of Health Center for Regenerative Medicine: putting science into practice.

    PubMed

    Rao, Mahendra

    2013-12-01

    The field of regenerative medicine has been revolutionized by breakthroughs in stem cell biology, gene engineering, and whole-genome sequencing. These advances are not only scientific or medical but have also advanced how we conceptualize regenerative medicine. The progenitive research that proceeded as well as a substantial part of the funding that supported these discoveries were provided by the National Institutes of Health (NIH). Now, perhaps more than ever, the NIH has a vital role to play in the translation of science into clinical practice. The NIH is uniquely positioned to coordinate interactions between the different institutes and other arms of the government, as well as international organizations. Efforts of researchers in the United States both within and without the NIH are supported by a number of mechanisms, including specialized workshops, and the support of developing small-scale industry. Additionally, the NIH has stepped up to provide necessary infrastructure in areas of regenerative medicine where the medical need might be apparent but might be currently infeasible or unattractive to private-sector investment. This article will discuss these perhaps lesser-known activities of the NIH, which I believe have continued and will continue to contribute to the role of stem cell research in translating science into regenerative medicine.

  15. 78 FR 43889 - Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ... go to: https://collaboration.fda.gov/sesdctrmpworkshop/ . If you have never attended an Adobe Connect... HUMAN SERVICES Food and Drug Administration Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine Products; Public Workshop AGENCY: Food and Drug Administration, HHS...

  16. Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine.

    PubMed

    Mizuno, Hiroshi; Tobita, Morikuni; Uysal, A Cagri

    2012-05-01

    The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed. Copyright © 2012 AlphaMed Press.

  17. A novel method to precisely assemble loose nanofiber structures for regenerative medicine applications.

    PubMed

    Beachley, Vince; Katsanevakis, Eleni; Zhang, Ning; Wen, Xuejun

    2013-02-01

    Polymer nanofibers are favorable for tissue engineering scaffolds because of their high surface-to-volume ratio and biomimicry of the extracellular matrix. Random and uniaxially oriented polymer nanofibers are easily fabricated by conventional electrospinning techniques; however, control over fiber organization within nanofiber structures is limited when they are collected directly from an electrospinning jet. The regenerative medicine applications of electrospun scaffolds could be expanded by developing assembly methods that allow better control of fiber organization. Here, a novel technique is presented that utilizes parallel automated tracks to orient and collect nanofibers from an electrospinning jet. The stabilized fibers are then subsequently assembled into desirable structures. It is difficult to assemble complex structures directly from an electrospinning jet because of high electrical charge and velocities, so this technology adds an intermediate step where nanofibers are immobilized on automated tracks. The result is a continuous steady-state delivery of static stabilized nanofibers that provides a unique and promising platform for automated post processing into useful nanofiber structures. This technique also allows for an indefinite amount of time, as determined by design parameters, for fibers to dry or cool before they contact other nanofibers in the collection site, thus eliminating potential for fiber-to-fiber adhesions even with slow evaporating solvents or high-temperature melts. To demonstrate potential in regenerative medicine applications, several nanofiber structures were fabricated, including: 2D structures with well-controlled fiber density; 3D loosely assembled aligned nanofiber structures with good cell penetration properties; and, complex layer-by-layer 3D aligned fiber structures assembled by integration with post-processing techniques.

  18. Microfluidic platform with four orthogonal and overlapping gradients for soluble compound screening in regenerative medicine research.

    PubMed

    Harink, Björn; Le Gac, Séverine; Barata, David; van Blitterswijk, Clemens; Habibovic, Pamela

    2015-02-01

    We present here a screening method based on a microfluidic platform, which can generate four orthogonal and overlapping concentration gradients of soluble compounds over a monolayer of cells, in combination with automated and in situ image analysis, for use in regenerative medicine research. The device includes a square chamber in which cells are grown, and four independent supply channels along the sides of the chamber, which are connected through an array of small diffusion channels. Compounds flown through the supply channels diffuse through diffusion channels into the chamber to create a gradient over the cell culture area. Further, the chamber is connected to two channels intended for introduction of cells and in situ staining. In this study, the dimensions of the different channels were optimized through finite element modeling to yield stable gradients, and two designs were used with gradients spanning 2.9-2.4 μM and 3.4-2.0 μM. Next, overlapping gradients were generated using four rhodamine-derived fluorescent dyes, and imaged using confocal microscopy. Finally, the platform was applied to assess the concentration-dependent response of an osteoblastic cell line exposed to a hypoxia-mimicking molecule phenanthroline, using an in situ fluorescent staining assay in combination with image analysis, applicable to closed microfluidic devices. The on-chip assay yielded results comparable to those observed in conventional culture, where a range of concentrations was tested in independent microwells. In the future, we intend to use this method to complement or replace current research approaches in screening soluble compounds for regenerative medicine, which are often based on one-sample-for-one-experiment principle.

  19. Stem cells and regenerative medicine for diabetes mellitus.

    PubMed

    Sumi, Shoichiro; Gu, Yuanjun; Hiura, Akihito; Inoue, Kazutomo

    2004-10-01

    A profound knowledge of the development and differentiation of pancreatic tissues, especially islets of Langerhans, is necessary for developing regenerative therapy for severe diabetes mellitus. A recent developmental study showed that PTF-1a is expressed in almost all parts of pancreatic tissues, in addition to PDX-1, a well-known transcription factor that is essential for pancreas development. Another study suggested that alpha cells and beta cells individually, but not sequentially, differentiated from neurogenin-3--expressing precursor cells. Under strong induction of pancreas regeneration, it is likely that pancreatic duct cells dedifferentiate to grow, express PDX-1, and re-differentiate toward other cell types including islet cells. Duct epithelium-like cells can be cultivated from crude pancreatic exocrine cells and can be induced to differentiate toward islet-like cell clusters under some culture conditions. These cell clusters made from murine pancreas have been shown to control hyperglycemia when transplanted into diabetic mice. Liver-derived oval cells and their putative precursor H-CFU-C have been shown to differentiate toward pancreatic cells. Furthermore, extrapancreatic cells contained in bone marrow and amniotic membrane are reported to become insulin-producing cells. However, their exact characterization and relationship between these cell types remain to be elucidated. Our recent study has shown that islet-like cell clusters can be differentiated from mouse embryonic stem cells. Transplantation of these clusters could ameliorate hyperglycemia of STZ-induced diabetic mice without forming teratomas. Interestingly, these cells expressed several genes specific to exocrine pancreatic tissue in addition to islet-related genes, suggesting that stable and efficient differentiation toward certain tissues can only be achieved through a process mimicking normal development of the tissue. Perhaps recent developments in these fields may rapidly lead to an

  20. Application of Stem Cell Technology in Dental Regenerative Medicine

    PubMed Central

    Feng, Ruoxue; Lengner, Chistopher

    2013-01-01

    Significance In this review, we summarize the current literature regarding the isolation and characterization of dental tissue-derived stem cells and address the potential of these cell types for use in regenerative cell transplantation therapy. Recent Advances Looking forward, platforms for the delivery of stem cells via scaffolds and the use of growth factors and cytokines for enhancing dental stem cell self-renewal and differentiation are discussed. Critical Issues We aim to understand the developmental origins of dental tissues in an effort to elucidate the molecular pathways governing the genesis of somatic dental stem cells. The advantages and disadvantages of several dental stem cells are discussed, including the developmental stage and specific locations from which these cells can be purified. In particular, stem cells from human exfoliated deciduous teeth may act as a very practical and easily accessibly reservoir for autologous stem cells and hold the most value in stem cell therapy. Dental pulp stem cells and periodontal ligament stem cells should also be considered for their triple lineage differentiation ability and relative ease of isolation. Further, we address the potentials and limitations of induced pluripotent stem cells as a cell source in dental regenerative. Future Directions From an economical and a practical standpoint, dental stem cell therapy would be most easily applied in the prevention of periodontal ligament detachment and bone atrophy, as well as in the regeneration of dentin-pulp complex. In contrast, cell-based tooth replacement due to decay or other oral pathology seems, at the current time, an untenable approach. PMID:24527351

  1. Pharmacovigilance of Regenerative Medicine Under the Amended Pharmaceutical Affairs Act in Japan.

    PubMed

    Inokuma, Yasuko

    2017-06-01

    Two Japanese regulatory agencies, the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency announced the implementation of a new review system called 'Conditional Approval,' specifically for the emerging field of regenerative medicine, in an amendment to the Pharmaceutical Affairs Act in 2014. Regenerative medicine was regulated in the category of 'Medical Devices' prior to the amendment and was not covered by the Relief Service, a system that provides financial aid to people who have experienced an adverse drug reaction and developed serious side effects as a result. Through the amendment, regenerative medicine is defined as a new category and is covered by the Relief Service under the amended Pharmaceutical Affairs Act, called the 'Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics' (PMD Act). This amendment allows the use of Relief Service data for pharmacovigilance activities, making the Relief Service the third adverse drug reaction reporting route in addition to the existing reporting routes from marketing authorization holders and healthcare providers. For optimum incorporation and use of this Relief Service data, earlier access should be allowed even before the reports from the Pharmaceuticals and Medical Devices Agency to the Ministry of Health, Labour and Welfare are finalized, which is mandatory under the current PMD Act.

  2. Umbilical cord blood: a trustworthy source of multipotent stem cells for regenerative medicine.

    PubMed

    Jaing, Tang-Her

    2014-01-01

    It is conservatively estimated that one in three individuals in the US might benefit from regenerative medicine therapy. However, the relation of embryonic stem cells (ESCs) to human blastocysts always stirs ethical, political, moral, and emotional debate over their use in research. Thus, for the reasonably foreseeable future, the march of regenerative medicine to the clinic will depend upon the development of non-ESC therapies. Current sources of non-ESCs easily available in large numbers can be found in the bone marrow, adipose tissue, and umbilical cord blood (UCB). UCB provides an immune-compatible source of stem cells for regenerative medicine. Owing to inconsistent results, it is certainly an important and clinically relevant question whether UCB will prove to be therapeutically effective. This review will show that UCB contains multiple populations of multipotent stem cells, capable of giving rise to hematopoietic, epithelial, endothelial, and neural tissues both in vitro and in vivo. Here we raise the possibility that due to unique immunological properties of both the stem cell and non-stem cell components of cord blood, it may be possible to utilize allogeneic cells for regenerative applications without needing to influence or compromise the recipient immune system.

  3. Designing biomaterials with immunomodulatory properties for tissue engineering and regenerative medicine

    PubMed Central

    Andorko, James I.

    2017-01-01

    Abstract Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune‐stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties—size, shape, chemical functionality—impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine. We begin by discussing what has been learned from studies conducted in the contexts of vaccines and immunotherapies. Next, research is highlighted that elucidates the properties of materials that polarize innate immune cells, including macrophages and dendritic cells, toward either inflammatory or wound healing phenotypes. We also discuss recent studies demonstrating that scaffolds used in tissue engineering applications can influence cells of the adaptive immune system—B and T cell lymphocytes—to promote regenerative tissue microenvironments. Through greater study of the intrinsic immunogenic features of implantable materials and scaffolds, new translational opportunities will arise to better control tissue engineering and regenerative medicine applications. PMID:28932817

  4. Advancing regenerative surgery in orthopaedic sports medicine: the critical role of the surgeon.

    PubMed

    Moran, Cathal J; Barry, Frank P; Maher, Suzanne A; Shannon, Fintan J; Rodeo, Scott A

    2012-04-01

    The constant desire to improve outcomes in orthopaedic sports medicine requires us to continuously consider the challenges faced in the surgical repair or reconstruction of soft tissue and cartilaginous injury. In many cases, surgical efforts targeted at restoring normal anatomy and functional status are ultimately impaired by the biological aspect of the natural history of these injuries, which acts as an obstacle to a satisfactory repair process after surgery. The clinical management of sports injuries and the delivery of appropriate surgical intervention are continuously evolving, and it is likely that the principles of regenerative medicine will have an increasing effect in this specialized field of orthopaedic practice going forward. Ongoing advances in arthroscopy and related surgical techniques should facilitate this process. In contrast to the concept of engineered replacement of entire tissues, it is probable that the earliest effect of regenerative strategies seen in clinical practice will involve biological augmentation of current operative techniques via a synergistic process that might be best considered "regenerative surgery." This article provides an overview of the principles of regenerative surgery in cartilage repair and related areas of orthopaedic surgery sports medicine. The possibilities and challenges of a gradual yet potential paradigm shift in treatment through the increased use of biological augmentation are considered. The translational process and critical role to be played by the specialist surgeon are also addressed. We conclude that increased understanding of the potential and challenges of regenerative surgery should allow those specializing in orthopaedic surgery sports medicine to lead the way in advancing the frontiers of biological strategies to enhance modern clinical care in an evidence-based manner.

  5. Engineering mesenchymal stem cells for regenerative medicine and drug delivery.

    PubMed

    Park, Ji Sun; Suryaprakash, Smruthi; Lao, Yeh-Hsing; Leong, Kam W

    2015-08-01

    Researchers have applied mesenchymal stem cells (MSC) to a variety of therapeutic scenarios by harnessing their multipotent, regenerative, and immunosuppressive properties with tropisms toward inflamed, hypoxic, and cancerous sites. Although MSC-based therapies have been shown to be safe and effective to a certain degree, the efficacy remains low in most cases when MSC are applied alone. To enhance their therapeutic efficacy, researchers have equipped MSC with targeted delivery functions using genetic engineering, therapeutic agent incorporation, and cell surface modification. MSC can be genetically modified virally or non-virally to overexpress therapeutic proteins that complement their innate properties. MSC can also be primed with non-peptidic drugs or magnetic nanoparticles for enhanced efficacy and externally regulated targeting, respectively. Furthermore, MSC can be functionalized with targeting moieties to augment their homing toward therapeutic sites using enzymatic modification, chemical conjugation, or non-covalent interactions. These engineering techniques are still works in progress, requiring optimization to improve the therapeutic efficacy and targeting effectiveness while minimizing any loss of MSC function. In this review, we will highlight the advanced techniques of engineering MSC, describe their promise and the challenges of translation into clinical settings, and suggest future perspectives on realizing their full potential for MSC-based therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Engineering Mesenchymal Stem Cells for Regenerative Medicine and Drug Delivery

    PubMed Central

    Park, Ji Sun; Suryaprakash, Smruthi; Lao, Yeh-Hsing; Leong, Kam W.

    2015-01-01

    Researchers have applied mesenchymal stem cells (MSC) to a variety of therapeutic scenarios by harnessing their multipotent, regenerative, and immunosuppressive properties with tropisms toward inflamed, hypoxic, and cancerous sites. Although MSC-based therapies have been shown to be safe and effective to a certain degree, the efficacy remains low in most cases when MSC are applied alone. To enhance their therapeutic efficacy, researchers have equipped MSC with targeted delivery functions using genetic engineering, therapeutic agent incorporation, and cell surface modification. MSC can be genetically modified virally or non-virally to overexpress therapeutic proteins that complement their innate properties. MSC can also be primed with non-peptidic drugs or magnetic nanoparticles for enhanced efficacy and externally regulated targeting, respectively. Furthermore, MSC can be functionalized with targeting moieties to augment their homing toward therapeutic sites using enzymatic modification, chemical conjugation, or non-covalent interactions. These engineering techniques are still works in progress, requiring optimization to improve the therapeutic efficacy and targeting effectiveness while minimizing any loss of MSC function. In this review, we will highlight the advanced techniques of engineering MSC, describe their promise and the challenges of translation into clinical settings, and suggest future perspectives on realizing their full potential for MSC-based therapy. PMID:25770356

  7. Pericytes and their potential in regenerative medicine across species.

    PubMed

    Esteves, C L; Donadeu, F X

    2017-09-20

    The discovery that pericytes are in vivo counterparts of Mesenchymal Stem/Stromal Cells (MSCs) has placed these perivascular cells in the research spotlight, bringing up hope for a well-characterized cell source for clinical applications, alternative to poorly defined, heterogeneous MSCs preparations currently in use. Native pericytes express typical MSC markers and, after isolation by fluorescence-activated cell sorting, display an MSC phenotype in culture. These features have been demonstrated in different species, including humans and horses, the main targets of regenerative treatments. Significant clinical potential of pericytes has been shown by transplantation of human cells into rodent models of tissue injury, and it is hoped that future studies will demonstrate clinical potential in veterinary species. Here, we provide an overview of the current knowledge on pericytes across different species including humans, companion and large animal models, in relation to their identification in different body tissues, methodology for prospective isolation, characterization, and potential for tissue regeneration. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  8. Promises and challenges of stem cell research for regenerative medicine.

    PubMed

    Power, Carl; Rasko, John E J

    2011-11-15

    In recent years, stem cells have generated increasing excitement, with frequent claims that they are revolutionizing medicine. For those not directly involved in stem cell research, however, it can be difficult to separate fact from fiction or realistic expectation from wishful thinking. This article aims to provide internists with a clear and concise introduction to the field. While recounting some scientific and medical milestones, the authors discuss the 3 main varieties of stem cells-adult, embryonic, and induced pluripotent-comparing their advantages and disadvantages for clinical medicine. The authors have sought to avoid the moral and political debates surrounding stem cell research, focusing instead on scientific and medical issues.

  9. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

    PubMed Central

    Correia, S. I.; Pereira, H.; Silva-Correia, J.; Van Dijk, C. N.; Espregueira-Mendes, J.; Oliveira, J. M.; Reis, R. L.

    2014-01-01

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to ‘conventional’ methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions. PMID:24352667

  10. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint.

    PubMed

    Correia, S I; Pereira, H; Silva-Correia, J; Van Dijk, C N; Espregueira-Mendes, J; Oliveira, J M; Reis, R L

    2014-03-06

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to 'conventional' methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions.

  11. The role of tissue engineering and biomaterials in cardiac regenerative medicine

    PubMed Central

    Zhao, Yimu; Feric, Nicole T.; Thavandiran, Nimalan; Nunes, Sara S.; Radisic, Milica

    2014-01-01

    In recent years, the development of three-dimensional engineered heart tissue (EHT) has made large strides forward due to advances in stem cell biology, materials science, pre-vascularization strategies and nanotechnology. As a result, the role of tissue engineering in cardiac regenerative medicine has become multi-faceted as new applications become feasible. Cardiac tissue engineering has long been established to have the potential to partially or fully restore cardiac function following cardiac injury. However, EHTs may also serve as surrogate human cardiac tissue for drug-related toxicity screening. Cardiotoxicity remains a major cause of drug withdrawal in the pharmaceutical industry. Unsafe drugs reach the market because pre-clinical evaluation is insufficient to weed out cardiotoxic drugs in all their forms. Bioengineering methods could provide functional and mature human myocardial tissues, i.e. physiologically relevant platforms, for screening the cardiotoxic effects of pharmaceutical agents and facilitate the discovery of new therapeutic agents. Finally, advances in induced pluripotent stem cells have made patient-specific EHTs possible, which opens up the possibility of personalized medicine. Herein, we give an overview of the present state of the art in cardiac tissue engineering, the challenges to the field and future perspectives. PMID:25442432

  12. Veterinary applications of induced pluripotent stem cells: regenerative medicine and models for disease?

    PubMed

    Cebrian-Serrano, Alberto; Stout, Tom; Dinnyes, Andras

    2013-10-01

    Induced pluripotent stem cells (iPSCs) can now be derived from a tissue biopsy and represent a promising new platform for disease modelling, drug and toxicity testing, biomarker development and cell-based therapies for regenerative medicine. In regenerative medicine, large animals may represent the best models for man, and thereby provide invaluable systems in which to test the safety and the potential of iPSCs. Hence, testing iPSCs in veterinary species may serve a double function, namely, developing therapeutic products for regenerative medicine in veterinary patients while providing valuable background information for human clinical trials. The production of iPSCs from livestock or wild species is attractive because it could improve efficiency and reduce costs in various fields, such as transgenic animal generation and drug development, preservation of biological diversity, and because it also offers an alternative to xenotransplantation for in vivo generation of organs. Although the technology of cellular reprogramming using the so-called 'Yamanaka factors' is in its peak expectation phase and many concerns still need to be addressed, the rapid technical progress suggests that iPSCs could contribute significantly to novel therapies in veterinary and biomedical practice in the near future. This review provides an overview of the potential applications of iPSCs in veterinary medicine.

  13. The potential role of regenerative medicine in the man-agement of traumatic patients.

    PubMed

    Moradi, Mahmoudreza; Hood, Brandy; Moradi, Marzieh; Atala, Anthony

    2015-01-01

    Traumatic injury represents the most common cause of death in ages 1 to 44 years and asignificant proportion of patients treated in hospital emergency wards each year. Unfortunately, for patients who survive their injuries, survival is not equal to complete recovery. Many traumatic injuries are difficult to treat with conventional therapy and result in permanent disability. In such situations, regenerative medicine has the potential to play an important role in recovery of function. Regenerative medicine is a field that seeks to maintain or restore function with the development of biological substitutes for diseased or damaged tissues. Several regenerative approaches are currently under investigation, with a few achieving clinical application. For example, engineered skin has gained FDA approval, and more than 20 tissue engineered skin substitutes are now commercially available. Other organ systems with promising animal models and small human series include the central and peripheral nervous systems, the musculoskeletal system, the respiratory and genitourinary tracts, and others. This paper will be a clinically oriented review of the regenerative approaches currently under investigation of special interest to those caring for traumatic patients. © 2015 KUMS, All rights reserved.

  14. The potential role of regenerative medicine in the management of traumatic patients

    PubMed Central

    Moradi, Mahmoudreza; Hood, Brandy; Moradi, Marzieh; Atala, Anthony

    2015-01-01

    Abstract: Traumatic injury represents the most common cause of death in ages 1 to 44 years and a significant proportion of patients treated in hospital emergency wards each year. Unfortunately, for patients who survive their injuries, survival is not equal to complete recovery. Many traumatic injuries are difficult to treat with conventional therapy and result in permanent disability. In such situations, regenerative medicine has the potential to play an important role in recovery of function. Regenerative medicine is a field that seeks to maintain or restore function with the development of biological substitutes for diseased or damaged tissues. Several regenerative approaches are currently under investigation, with a few achieving clinical application. For example, engineered skin has gained FDA approval, and more than 20 tissue engineered skin substitutes are now commercially available. Other organ systems with promising animal models and small human series include the central and peripheral nervous systems, the musculoskeletal system, the respiratory and genitourinary tracts, and others. This paper will be a clinically oriented review of the regenerative approaches currently under investigation of special interest to those caring for traumatic patients. PMID:25618439

  15. Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation

    PubMed Central

    Nowacki, Maciej; Nazarewski, Łukasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L.; Drewa, Tomasz

    2016-01-01

    On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression. PMID:27695507

  16. A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine.

    PubMed

    Asuelime, Grace E; Shi, Yanhong

    2012-08-01

    The field of regenerative medicine is rapidly gaining momentum as an increasing number of reports emerge concerning the induced conversions observed in cellular fate reprogramming. While in recent years, much attention has been focused on the conversion of fate-committed somatic cells to an embryonic-like or pluripotent state, there are still many limitations associated with the applications of induced pluripotent stem cell reprogramming, including relatively low reprogramming efficiency, the times required for the reprogramming event to take place, the epigenetic instability, and the tumorigenicity associated with the pluripotent state. On the other hand, lineage reprogramming involves the conversion from one mature cell type to another without undergoing conversion to an unstable intermediate. It provides an alternative approach in regenerative medicine that has a relatively lower risk of tumorigenesis and increased efficiency within specific cellular contexts. While lineage reprogramming provides exciting potential, there is still much to be assessed before this technology is ready to be applied in a clinical setting.

  17. AMNIOTIC FLUID STEM CELLS: THE KNOWN, THE UNKNOWN AND POTENTIAL REGENERATIVE MEDICINE APPLICATIONS.

    PubMed

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-12-23

    The amniotic fluid has been identified as an untapped source of cells with broad potential, which possess immunomodulatory properties and don't have the ethical and legal limitations of embryonic stem cells. CD117(c-Kit)+ cells selected from amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, making them ideal candidates for regenerative medicine applications. Moreover, their ability to engraft in injured organs and modulate immune and repair responses of host tissues, suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases. Although significant questions remain regarding the origin, heterogeneous phenotype and expansion potential of amniotic fluid stem cells, evidence to date supports their potential role as a valuable stem cell source for the field of regenerative medicine. This article is protected by copyright. All rights reserved.

  18. Tissue Engineering and Regenerative Medicine: Recent Innovations and the Transition to Translation

    PubMed Central

    Fisher, Matthew B.

    2013-01-01

    The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent “hot topics” and transformative publications within the field. Through this process, several key themes emerged: (1) tissue engineering: grafts and materials, (2) regenerative medicine: scaffolds and factors that control endogenous tissue formation, (3) clinical trials, and (4) novel cell sources: induced pluripotent stem cells. Within these focus areas, we summarize the highly impactful articles that emerged from our objective analysis and review additional recent publications to augment and expand upon these key themes. Finally, we discuss where the TERM field may be headed and how to monitor such a broad-based and ever-expanding community. PMID:23253031

  19. Regenerative medicine: shedding light into the link between aging and cancer.

    PubMed

    Marongiu, Fabio; Serra, Maria Paola; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

    2017-03-02

    The evidence linking aging and cancer is overwhelming. Findings emerging from the field of regenerative medicine reinforce the notion that aging and cancer are profoundly interrelated in their pathogenetic pathways. We discuss evidence to indicate that age-associated alterations in the tissue microenvironment contribute to the emergence of a neoplastic-prone tissue landscape, which is able to support the selective growth of pre-neoplastic cell populations. Interestingly, tissue contexts that are able to select for the growth of pre-neoplastic cells, including the aged liver microenvironment, are also supportive for the clonal expansion of normal, homotypic, transplanted cells. This suggests that the growth of normal and pre-neoplastic cells is possibly driven by similar mechanisms, implying that strategies based on principles of regenerative medicine might be applicable to modulate neoplastic disease.

  20. Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies

    PubMed Central

    2014-01-01

    New curative therapies for severe liver disease are urgently needed in both the human and veterinary clinic. It is important to find new treatment modalities which aim to compensate for the loss of parenchymal tissue and to repopulate the liver with healthy hepatocytes. A prime focus in regenerative medicine of the liver is the use of adult liver stem cells, or hepatic progenitor cells (HPCs), for functional recovery of liver disease. This review describes recent developments in HPC research in dog and cat and compares these findings to experimental rodent studies and human pathology. Specifically, the role of HPCs in liver regeneration, key components of the HPC niche, and HPC activation in specific types of canine and feline liver disease will be reviewed. Finally, the potential applications of HPCs in regenerative medicine of the liver are discussed and a potential role is suggested for dogs as first target species for HPC-based trials. PMID:24946932

  1. The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

    PubMed

    Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

    2015-11-01

    Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

  2. Biological roles of glial fibrillary acidic protein as a biomarker in cartilage regenerative medicine.

    PubMed

    Kanazawa, Sanshiro; Nishizawa, Satoru; Takato, Tsuyoshi; Hoshi, Kazuto

    2017-11-01

    Glial fibrillary acidic protein (GFAP) is an intermediate filament that is expressed in specifically expressed auricular chondrocytes, which are good cell sources of cartilage regenerative medicine. Although our group uses GFAP as a biomarker of matrix production in the cultured auricular chondrocytes, the biological roles of GFAP in auricular chondrocytes has remained unknown. In this study, we demonstrated the biological functions of GFAP in the human and mouse derived auricles to clarify the significance and role with the chondrocytes of GFAP in order to provide useful information for reliable and safe regenerative medicine. We examined the cell responses to stretch stress for these chondrocytes and completed a nuclear morphological analysis. Based on these results, GFAP seems to support the resistance to severe mechanical stress in the tissue which physiologically suffers from a stretch overload, and plays pivotal roles in the conservation of cell structures and functions through the maintenance of nuclear morphology. © 2017 Wiley Periodicals, Inc.

  3. The fetal liver as cell source for the regenerative medicine of liver and pancreas

    PubMed Central

    Semeraro, Rossella; Cardinale, Vincenzo; Carpino, Guido; Gentile, Raffaele; Napoli, Cristina; Venere, Rosanna; Gatto, Manuela; Brunelli, Roberto; Gaudio, Eugenio

    2013-01-01

    Patients affected by liver diseases and diabetes mellitus are in need for sources of new cells to enable a better transition into clinic programs of cell therapy and regenerative medicine. In this setting, fetal liver is becoming the most promising and available source of cells. Fetal liver displays unique characteristics given the possibility to isolate cell populations with a wide spectrum of endodermal differentiation and, the co-existence of endodermal and mesenchymal-derived cells. Thus, the fetal liver is a unique and highly available cell source contemporarily candidate for the regenerative medicine of both liver and pancreas. The purpose of this review is to revise the recent literature on the different stem cells populations isolable from fetal liver and candidate to cell therapy of liver diseases and diabetes and to discuss advantages and limitation with respect to other cell sources. PMID:25332958

  4. Concise Review: The U.S. Food and Drug Administration and Regenerative Medicine.

    PubMed

    Witten, Celia M; McFarland, Richard D; Simek, Stephanie L

    2015-12-01

    Regenerative medicine (RM) is a popular term for a field of scientific and medical research. There is not one universally accepted definition of RM, but it is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. RM products have the potential to provide treatments for a number of unmet needs but have substantial scientific and regulatory challenges that need to be addressed for this potential to be fully realized. FDA has established formal regulatory definitions for biologics, medical devices, and combination products, as well as human cells and tissues. Regenerative medicine products regulated by FDA are classified on the basis of these definitions, and the classification forms the basis for determining the regulatory requirements to each specific product. FDA regulations are generally written to allow the agency flexibility to accommodate new scientific questions raised by novel and evolving technologies. FDA efforts to facilitate product development in this novel and promising area include working with individual sponsors, interacting with the scientific and industry communities, participating in standards development, and developing policy and guidance. Regenerative medicine is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. This article provides an overview of the efforts of the U.S. Food and Drug Administration (FDA) to facilitate product development in the field commonly known was regenerative medicine. It provides an introduction to the processes by which FDA works with individual sponsors, interacts with the scientific and industry communities, participates in standards development, and develops formal FDA policy and guidance. ©AlphaMed Press.

  5. Concise Review: The U.S. Food and Drug Administration and Regenerative Medicine

    PubMed Central

    McFarland, Richard D.; Simek, Stephanie L.

    2015-01-01

    Regenerative medicine (RM) is a popular term for a field of scientific and medical research. There is not one universally accepted definition of RM, but it is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. RM products have the potential to provide treatments for a number of unmet needs but have substantial scientific and regulatory challenges that need to be addressed for this potential to be fully realized. FDA has established formal regulatory definitions for biologics, medical devices, and combination products, as well as human cells and tissues. Regenerative medicine products regulated by FDA are classified on the basis of these definitions, and the classification forms the basis for determining the regulatory requirements to each specific product. FDA regulations are generally written to allow the agency flexibility to accommodate new scientific questions raised by novel and evolving technologies. FDA efforts to facilitate product development in this novel and promising area include working with individual sponsors, interacting with the scientific and industry communities, participating in standards development, and developing policy and guidance. Significance Regenerative medicine is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. This article provides an overview of the efforts of the U.S. Food and Drug Administration (FDA) to facilitate product development in the field commonly known was regenerative medicine. It provides an introduction to the processes by which FDA works with individual sponsors, interacts with the scientific and industry communities, participates in standards development, and develops formal FDA policy and guidance. PMID:26494784

  6. Steering a New Course for Stem Cell Research: NIH's Intramural Center for Regenerative Medicine

    PubMed Central

    Collins, Francis S.

    2012-01-01

    Summary The phenomenal progress made in stem cell biology in the past few years has infused the field of regenerative medicine with a great deal of scientific enthusiasm. However, along with the excitement of discovery comes a new sense of translational urgency. The prospect of using embryonic and induced pluripotent stem cell tools and technologies to produce cell-based therapies and other treatments is no longer a distant dream; it is a very real opportunity that demands our attention today. As with most new fields, regenerative medicine has experienced some significant growing pains, and we have identified a number of key obstacles to progress. Given our role as the lead U.S. biomedical research agency and the world's largest supporter of medical research, the National Institutes of Health (NIH) has a responsibility to find ways to reduce or remove many of these obstacles and, consequently, has—and continues—to respond to these challenges in a variety of ways. In this brief essay, we will review our progress and highlight a new development: the founding of a Center for Regenerative Medicine on the NIH campus. PMID:23197635

  7. Translating cell-based regenerative medicines from research to successful products: challenges and solutions.

    PubMed

    Bayon, Yves; Vertès, Alain A; Ronfard, Vincent; Egloff, Matthieu; Snykers, Sarah; Salinas, Gabriella Franco; Thomas, Robert; Girling, Alan; Lilford, Richard; Clermont, Gaelle; Kemp, Paul

    2014-08-01

    The Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart intend to address the specific challenges and needs facing the industry in translating academic research into commercial products. Over the last 3 years, the TERMIS-EU Industry Committee has worked with commercial bodies to deliver programs that encourage academics to liaise with industry in proactive collaborations. The TERMIS-EU 2013 Industry Symposium aimed to build on this commercial agenda by focusing on two topics: Operations Management (How to move a process into the good manufacturing practice [GMP] environment) and Clinical Translation (Moving a GMP process into robust trials). These topics were introduced by providing the synergistic business perspective of partnering between the multiple regenerative medicine stakeholders, throughout the life cycle of product development. Seven industry leaders were invited to share their experience, expertise, and strategies. Due to the complex nature of regenerative medicine products, partnering for their successful commercial development seems inevitable to overcome all obstacles by sharing experiences and expertise of all stakeholders. When ideally implemented, the "innovation quotient" of a virtual team resulting from the combination of internal and external project teams can be maximized through maximizing the three main dimensions: core competences, technology portfolio, and alliance management.

  8. Attenuated Innate Immunity in Embryonic Stem Cells and Its Implications in Developmental Biology and Regenerative Medicine.

    PubMed

    Guo, Yan-Lin; Carmichael, Gordon G; Wang, Ruoxing; Hong, Xiaoxiao; Acharya, Dhiraj; Huang, Faqing; Bai, Fengwei

    2015-11-01

    Embryonic stem cells (ESCs) represent a promising cell source for regenerative medicine. Intensive research over the past 2 decades has led to the feasibility of using ESC-differentiated cells (ESC-DCs) in regenerative medicine. However, increasing evidence indicates that ESC-DCs generated by current differentiation methods may not have equivalent cellular functions to their in vivo counterparts. Recent studies have revealed that both human and mouse ESCs as well as some types of ESC-DCs lack or have attenuated innate immune responses to a wide range of infectious agents. These findings raise important concerns for their therapeutic applications since ESC-DCs, when implanted to a wound site of a patient, where they would likely be exposed to pathogens and inflammatory cytokines. Understanding whether an attenuated immune response is beneficial or harmful to the interaction between host and grafted cells becomes an important issue for ESC-based therapy. A substantial amount of recent evidence has demonstrated that the lack of innate antiviral responses is a common feature to ESCs and other types of pluripotent cells. This has led to the hypothesis that mammals may have adapted different antiviral mechanisms at different stages of organismal development. The underdeveloped innate immunity represents a unique and uncharacterized property of ESCs that may have important implications in developmental biology, immunology, and in regenerative medicine.

  9. Cell Processing Engineering for Regenerative Medicine : Noninvasive Cell Quality Estimation and Automatic Cell Processing.

    PubMed

    Takagi, Mutsumi

    2016-01-01

    The cell processing engineering including automatic cell processing and noninvasive cell quality estimation of adherent mammalian cells for regenerative medicine was reviewed. Automatic cell processing necessary for the industrialization of regenerative medicine was introduced. The cell quality such as cell heterogeneity should be noninvasively estimated before transplantation to patient, because cultured cells are usually not homogeneous but heterogeneous and most protocols of regenerative medicine are autologous system. The differentiation level could be estimated by two-dimensional cell morphology analysis using a conventional phase-contrast microscope. The phase-shifting laser microscope (PLM) could determine laser phase shift at all pixel in a view, which is caused by the transmitted laser through cell, and might be more noninvasive and more useful than the atomic force microscope and digital holographic microscope. The noninvasive determination of the laser phase shift of a cell using a PLM was carried out to determine the three-dimensional cell morphology and estimate the cell cycle phase of each adhesive cell and the mean proliferation activity of a cell population. The noninvasive discrimination of cancer cells from normal cells by measuring the phase shift was performed based on the difference in cytoskeleton density. Chemical analysis of the culture supernatant was also useful to estimate the differentiation level of a cell population. A probe beam, an infrared beam, and Raman spectroscopy are useful for diagnosing the viability, apoptosis, and differentiation of each adhesive cell.

  10. Clinical research skills development program in cell-based regenerative medicine.

    PubMed

    Schulman, Ivonne Hernandez; Suncion, Viky; Karantalis, Vasileios; Balkan, Wayne; Hare, Joshua M

    2015-02-01

    Cell-based therapy aimed at restoring organ function is one of the most exciting and promising areas of medical research. However, a novel intervention like cell-based therapy requires physician education and training. An increasing number of physicians untrained in regenerative medicine are using cell-based therapy to treat patients for a wide variety of chronic illnesses. The current lack of training for physicians in this area combined with the sharply increasing practice of regenerative medicine is concerning for a number of reasons, namely potential harm to patients and avoidable conflicts between governmental regulatory agencies and physicians. Academic medical fellowship training programs are needed that specifically prepare physicians for treating patients with cell-based therapies for various organ systems and chronic diseases. The National Heart, Lung, and Blood Institute established the Cardiovascular Cell Therapy Network to design and conduct clinical trials that advance the field of cell-based therapy for patients with cardiovascular disease. As part of the network, a two-year Clinical Research Skills Development Program was supported at two centers with the goal of training early career investigators in cell-based clinical and translational research. In this review, we describe the implementation of this training program at our institution with the purpose of promoting the further development of academic fellowship programs in cell-based regenerative medicine.

  11. Advanced Tissue Sciences Inc.: learning from the past, a case study for regenerative medicine.

    PubMed

    Pangarkar, Nitin; Pharoah, Marc; Nigam, Avinav; Hutmacher, Dietmar W; Champ, Simon

    2010-09-01

    On 31st March 2003 Advanced Tissue Sciences (ATS) was liquidated, with the effect that in excess of US$300 million of stakeholder financing was destroyed. Although successful in the development of breakthrough technologies in the regenerative medicine arena and the building of a substantial portfolio of patents, the company never made a profit. In this case study, ATS’ business strategy, market and competitive environment will be discussed in the context of the company’s historical development. A number of important lessons from this case are discussed. From a management perspective the most critical lesson is the importance of effective financial planning and management of costs, and in particular R&D costs, including the significant costs associated with clinical trials. In addition, a clear strategic focus is extremely important due to the significant resources required in the development of a new therapy. From an investor’s perspective the lessons to be gathered from the ATS case are related to the risk involved in investing in the field of regenerative medicine. This case indicates that both professional and private investors did not fully question the validity of ATS’ business strategy and financial forecasts. A clear and focused strategy based on long-term investor commitment is essential for the successful commercialization of regenerative medicine.

  12. The endometrium as a source of mesenchymal stem cells for regenerative medicine.

    PubMed

    Mutlu, Levent; Hufnagel, Demetra; Taylor, Hugh S

    2015-06-01

    Stem cell therapies have opened new frontiers in medicine with the possibility of regenerating lost or damaged cells. Embryonic stem cells, induced pluripotent stem cells, hematopoietic stem cells, and mesenchymal stem cells have been used to derive mature cell types for tissue regeneration and repair. However, the endometrium has emerged as an attractive, novel source of adult stem cells that are easily accessed and demonstrate remarkable differentiation capacity. In this review, we summarize our current understanding of endometrial stem cells and their therapeutic potential in regenerative medicine.

  13. The Endometrium as a Source of Mesenchymal Stem Cells for Regenerative Medicine1

    PubMed Central

    Mutlu, Levent; Hufnagel, Demetra; Taylor, Hugh S.

    2015-01-01

    Stem cell therapies have opened new frontiers in medicine with the possibility of regenerating lost or damaged cells. Embryonic stem cells, induced pluripotent stem cells, hematopoietic stem cells, and mesenchymal stem cells have been used to derive mature cell types for tissue regeneration and repair. However, the endometrium has emerged as an attractive, novel source of adult stem cells that are easily accessed and demonstrate remarkable differentiation capacity. In this review, we summarize our current understanding of endometrial stem cells and their therapeutic potential in regenerative medicine. PMID:25904012

  14. Current advances in the generation of human iPS cells: implications in cell-based regenerative medicine.

    PubMed

    Revilla, Ana; González, Clara; Iriondo, Amaia; Fernández, Bárbara; Prieto, Cristina; Marín, Carlos; Liste, Isabel

    2016-11-01

    Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd.

  15. 3D Biofabrication Strategies for Tissue Engineering and Regenerative Medicine

    PubMed Central

    Bajaj, Piyush; Schweller, Ryan M.; Khademhosseini, Ali; West, Jennifer L.; Bashir, Rashid

    2014-01-01

    Over the past several decades, there has been an ever-increasing demand for organ transplants. However, there is a severe shortage of donor organs, and as a result of the increasing demand, the gap between supply and demand continues to widen. A potential solution to this problem is to grow or fabricate organs using biomaterial scaffolds and a person’s own cells. Although the realization of this solution has been limited, the development of new biofabrication approaches has made it more realistic. This review provides an overview of natural and synthetic biomaterials that have been used for organ/tissue development. It then discusses past and current biofabrication techniques, with a brief explanation of the state of the art. Finally, the review highlights the need for combining vascularization strategies with current biofabrication techniques. Given the multitude of applications of biofabrication technologies, from organ/tissue development to drug discovery/screening to development of complex in vitro models of human diseases, these manufacturing technologies can have a significant impact on the future of medicine and health care. PMID:24905875

  16. [Internationalization, science and health: global regenerative medicine and the parallel markets].

    PubMed

    Acero, Liliana

    2015-02-01

    Regenerative medicine involves a paradigm change due to organism regeneration at cellular and tissue level - a controversial contemporary issue and difficult to regulate. This article presents a summary of the main scientific, economic, social and regulatory global trends, analyzed according to relevant theoretical dilemmas in medical anthropology and in the sociology of science and health. This is especially true of the construction of a 'collective frame of reference' on the new biological and ontological entities, the shaping of biological citizenship, and governance through uncertainty. Empirical evidence is also presented on a key aspect in regulation and governance, namely the emergence of a new transnational demand in health research through the establishment of parallel markets for ova and experimental cellular therapies. Qualitative data collected for a broader research paper is analyzed, as well as journal reviews and information gathered during interviews with international leaders. The paper concludes with a discussion on the importance on international governance of clinical trials and on further exploration, towards a multilevel harmonization of a diversity of normative practices.

  17. Cell culture models of higher complexity in tissue engineering and regenerative medicine.

    PubMed

    James Kirkpatrick, Charles; Fuchs, Sabine; Iris Hermanns, Maria; Peters, Kirsten; Unger, Ronald E

    2007-12-01

    Cell culture techniques have tended to be used in biomaterial research as a screening method prior to embarking on specific in vivo experimentation. This presentation aims at showing that it is possible to develop more sophisticated in vitro systems using primary human cells in co-culture with other cell types and biomaterials in a three-dimensional setting. While the predictive value of such systems is still not proven these models can be employed to unravel the complexity of biological systems in order to understand molecular mechanisms of cell-cell and cell-material interactions. The brief overview is under the headings of basic principles of relevant culture systems, the study of inflammation and the healing response, scenarios for specific biomaterial applications and future directions. How human endothelial cells can be usefully incorporated into more complex cell culture models is presented as an example of how relevant questions in tissue engineering and regenerative medicine can be addressed. The central tenet of this paper is that it is possible to refine in vitro methodology using cells of human origin to establish relevant assay systems that more closely simulate the cellular and molecular microenvironment encountered in a specific situation of regeneration using biomaterials.

  18. Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

    PubMed

    Reinke, Simon; Dienelt, Anke; Blankenstein, Antje; Duda, Georg N; Geissler, Sven

    2016-01-01

    Regenerative medicine aims to replace lost cells and to restore damaged tissues and organs by either tissue-engineering approaches or stimulation of endogenous processes. Due to their biological properties, stem cells promise to be an effective source for such strategies. Especially adult multipotent stem cells (ASCs) are believed to be applicable in a broad range of therapies for the treatment of multifactorial diseases or age-related degeneration, although the molecular and cellular mechanisms underlying their regenerative function are often hardly described. Moreover, in some demanding clinical situations their efficiency remains limited. Thus, a basic understanding of ASCs regenerative function, their complex interplay with their microenvironment and how compromising conditions interfere with their efficiency is mandatory for any regenerative strategy. Concerning this matter, the impact of patient-specific constraints are often underestimated in research projects and their influence on the study results disregarded. Thus, researchers are urgently depending on well-characterized tissue samples or cells that are connected with corresponding donor information, such as secondary diseases, medication. Here, we outline principle pitfalls during experimental studies using human samples, and describe a potential strategy to overcome these challenges by establishing a core unit for cell and tissue harvesting. This facility aims to bridge the gap between clinic and research laboratories by the provision of a direct link to the clinical operating theatres. Such a strategy clearly supports basic and clinical research in the conduct of their studies and supplies highly characterized human samples together with the corresponding donor information.

  19. First pulse effect self-suppression picosecond regenerative amplifier (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Fan, Haitao; Chang, Liang; Zhang, Yi; Yao, Siyi; Lu, Wei; Yang, Xiaohong

    2017-03-01

    First pulse effect, commonly seen in nanosecond cavity-dumped lasers and picosecond regenerative amplifiers, not only leads to degradation of processing quality, but also acts as potential threat to optical switching elements. Several methods have been developed to suppress that effect, including electronic controls, polarization controls, and diffraction controls. We present a new way for first pulse self-suppression without any additional components. By carefully arranging the cavity mirror of a regenerative amplifier, we realized `parasitic lasing like' radiation. When the regenerative amplifier works in `operation ready' status, the parasitic lasing occurs and prevents the gain crystal from saturation. When the regenerative amplifier starts working and amplifying pulses, the first pulse in a pulse train will not get much more gain and energy than pulses following it. As parasitic lasing disappears at the same time, the average output power of the amplifier does not significantly reduce. This cost effective method does not require any additional component. In addition, as it is not polarization dependent, this method is widely suitable for different kinds of regenerative amplifiers. It's the easiest and cheapest way to suppress first pulse effect, to the best of our knowledge.

  20. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases.

    PubMed

    Weiss, Daniel J

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases.

  1. Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

    PubMed

    Pina, Sandra; Oliveira, Joaquim M; Reis, Rui L

    2015-02-18

    Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.

  2. Care of rodent models used for preclinical evaluation of tissue-engineered/regenerative medicine product candidates.

    PubMed

    Mihalko, Kim L

    2013-01-01

    The pre-, peri-, and postoperative care of animal surgical models used for testing tissue engineering/regenerative medicine product candidates includes the thoughtful consideration of several important factors. It must ensure the health and comfort of the animals and the success and reproducibility of the model. In order to reduce the number of animals needed in creating the model and to reduce costs, a preliminary evaluation of surgical procedures and instruments should be performed on cadavers. Once a minimal level of proficiency has been acquired, non-survival surgeries should be executed successfully before attempting survival surgeries. Planning ahead is crucial and will involve all aspects of the animal's care such as allowing the animal to become accustomed to soft foods (as in the case of gastrointestinal surgeries), planning appropriate pain management, and the use of positive reinforcement. We present specific examples of pre-, peri- and post-operative care of rodents using our experiences in developing tissue engineering products for kidney, esophagus, small intestine and lung.

  3. Development of a New Tool for 3D Modeling for Regenerative Medicine

    PubMed Central

    Mattoli, Filippo; Tiribuzi, Roberto; D'Angelo, Francesco; di Girolamo, Ilaria; Quattrocelli, Mattia; Montesano, Simona; Crispoltoni, Lucia; Oikonomou, Vasileios; Cusella De Angelis, Maria Gabriella; Marconi, Peggy; Orlacchio, Antonio; Sampaolesi, Maurilio; Martino, Sabata; Orlacchio, Aldo

    2011-01-01

    The effectiveness of therapeutic treatment based on regenerative medicine for degenerative diseases (i.e., neurodegenerative or cardiac diseases) requires tools allowing the visualization and analysis of the three-dimensional (3D) distribution of target drugs within the tissue. Here, we present a new computational procedure able to overcome the limitations of visual analysis emerging by the examination of a molecular signal within images of serial tissue/organ sections by using the conventional techniques. Together with the 3D anatomical reconstitution of the tissue/organ, our framework allows the detection of signals of different origins (e.g., marked generic molecules, colorimetric, or fluorimetric substrates for enzymes; microRNA; recombinant protein). Remarkably, the application does not require the employment of specific tracking reagents for the imaging analysis. We report two different representative applications: the first shows the reconstruction of a 3D model of mouse brain with the analysis of the distribution of the β-Galactosidase, the second shows the reconstruction of a 3D mouse heart with the measurement of the cardiac volume. PMID:21776249

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

    PubMed Central

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

    2009-01-01

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

  5. Development of a New Tool for 3D Modeling for Regenerative Medicine.

    PubMed

    Mattoli, Filippo; Tiribuzi, Roberto; D'Angelo, Francesco; di Girolamo, Ilaria; Quattrocelli, Mattia; Montesano, Simona; Crispoltoni, Lucia; Oikonomou, Vasileios; Cusella De Angelis, Maria Gabriella; Marconi, Peggy; Orlacchio, Antonio; Sampaolesi, Maurilio; Martino, Sabata; Orlacchio, Aldo

    2011-01-01

    The effectiveness of therapeutic treatment based on regenerative medicine for degenerative diseases (i.e., neurodegenerative or cardiac diseases) requires tools allowing the visualization and analysis of the three-dimensional (3D) distribution of target drugs within the tissue. Here, we present a new computational procedure able to overcome the limitations of visual analysis emerging by the examination of a molecular signal within images of serial tissue/organ sections by using the conventional techniques. Together with the 3D anatomical reconstitution of the tissue/organ, our framework allows the detection of signals of different origins (e.g., marked generic molecules, colorimetric, or fluorimetric substrates for enzymes; microRNA; recombinant protein). Remarkably, the application does not require the employment of specific tracking reagents for the imaging analysis. We report two different representative applications: the first shows the reconstruction of a 3D model of mouse brain with the analysis of the distribution of the β-Galactosidase, the second shows the reconstruction of a 3D mouse heart with the measurement of the cardiac volume.

  6. Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases

    PubMed Central

    Weiss, Daniel J.

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPD), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the 3rd leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and chronic obstructive pulmonary disease (COPD) with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been utilized to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy based clinical trials in lung diseases. PMID:23959715

  7. The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases.

    PubMed

    Lescaudron, L; Naveilhan, P; Neveu, I

    2012-01-01

    Cell transplantation has been proposed as a means of replacing specific cell populations lost through neurodegenerative processes such as that seen in Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has been observed in a number of Parkinson and Huntington's patients transplanted with freshly isolated fetal brain tissue but such restorative approach is greatly hampered by logistic and ethical concerns relative to the use of fetal tissue, in addition to potential side effects that remain to be controlled. In this context, stem cells that are capable of self-renewal and can differentiate into neurons, have received a great deal of interest, as demonstrated by the numerous studies based on the transplantation of neural stem/progenitor cells, embryonic stem cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's diseases. More recently, the induction of pluripotent stem cells from somatic adult cells has raised a new hope for the treatment of neurodegenerative diseases. In the present article, we review the main experimental approaches to assess the efficiency of cell-based therapy for Parkinson's or Huntington's diseases, and discuss the recent advances in using stem cells to replace lost dopaminergic mesencephalic or striatal neurons. Characteristics of the different stem cells are extensively examined with a special attention to their ability of producing neurotrophic or immunosuppressive factors, as these may provide a favourable environment for brain tissue repair and long-term survival of transplanted cells in the central nervous system. Thus, stem cell therapy can be a valuable tool in regenerative medicine.

  8. Emerging Roles for Extracellular Vesicles in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Lamichhane, Tek N.; Sokic, Sonja; Schardt, John S.; Raiker, Rahul S.; Lin, Jennifer W.

    2015-01-01

    Extracellular vesicles (EVs)—comprising a heterogeneous population of cell-derived lipid vesicles including exosomes, microvesicles, and others—have recently emerged as both mediators of intercellular information transfer in numerous biological systems and vehicles for drug delivery. In both roles, EVs have immense potential to impact tissue engineering and regenerative medicine applications. For example, the therapeutic effects of several progenitor and stem cell-based therapies have been attributed primarily to EVs secreted by these cells, and EVs have been recently reported to play direct roles in injury-induced tissue regeneration processes in multiple physiological systems. In addition, EVs have been utilized for targeted drug delivery in regenerative applications and possess unique potential to be harnessed as patient-derived drug delivery vehicles for personalized medicine. This review discusses EVs in the context of tissue repair and regeneration, including their utilization as drug carriers and their crucial role in cell-based therapies. Furthermore, the article highlights the growing need for bioengineers to understand, consider, and ultimately design and specifically control the activity of EVs to maximize the efficacy of tissue engineering and regenerative therapies. PMID:24957510

  9. Great expectations: private sector activity in tissue engineering, regenerative medicine, and stem cell therapeutics.

    PubMed

    Lysaght, Michael J; Jaklenec, Ana; Deweerd, Elizabeth

    2008-02-01

    This report draws upon data from a variety of sources to provide a detailed estimate of the current scope of private sector development and commercial activity in the aggregate field comprising tissue engineering, regenerative medicine, and stem cell therapeutics. Economic activity has grown a remarkable fivefold in the past 5 years. As of mid-2007 approximately 50 firms or business units with over 3000 employees offered commercial tissue-regenerative products or services with generally profitable annual sales in excess of $1.3 billion. Well over a million patients have been treated with these products. In addition, 110 development-stage companies with over 55 products in FDA-level clinical trials and other preclinical stages employed approximately 2500 scientists or support personnel and spent 850 million development dollars in 2007. These totals represent a remarkable recovery from the downturn of 2000-2002, at which time tissue engineering was in shambles because of disappointing product launches, failed regulatory trials, and the general investment pullback following the dot-com crash. Commercial success has resulted in large measure from identification of products that are achievable with available technology and under existing regulatory guidelines. Development-stage firms have become much more adept at risk management. The resilience of the field, as well as its current breadth and diversity, augurs well for the future of regenerative medicine.

  10. Dental stem cells: recent progresses in tissue engineering and regenerative medicine.

    PubMed

    Botelho, João; Cavacas, Maria Alzira; Machado, Vanessa; Mendes, José João

    2017-12-01

    Since the disclosure of adult mesenchymal stem cells (MSCs), there have been an intense investigation on the characteristics of these cells and their potentialities. Dental stem cells (DSCs) are MSC-like populations with self-renewal capacity and multidifferentiation potential. Currently, there are five main DSCs, dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs) and dental follicle precursor cells (DFPCs). These cells are extremely accessible, prevail during all life and own an amazing multipotency. In the past decade, DPSCs and SHED have been thoroughly studied in regenerative medicine and tissue engineering as autologous stem cells therapies and have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and auto-immune conditions, in both animal and human models, and most recently some of them in human clinical trials. In this review, we focus the characteristics, the multiple roles of DSCs and its potential translation to clinical settings. These new insights of the apparently regenerative aptitude of these DSCs seems quite promising to investigate these cells abilities in a wide variety of pathologies. Key messages Dental stem cells (DSCs) have a remarkable self-renewal capacity and multidifferentiation potential; DSCs are extremely accessible and prevail during all life; DSCs, as stem cells therapies, have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and autoimmune conditions; DSCs are becoming extremely relevant in tissue engineering and regenerative medicine.

  11. Armed Forces Institute of Regenerative Medicine Annual Report 2010

    DTIC Science & Technology

    2011-01-01

    Functional Scaffold for Musculoskeletal Repair and Delivery of Therapeutic Agents.........................................45 Project 4.4.3b, RCCC...warfighter. These therapies will (1) regenerate functional bone and cartilage to calva- rial-, upper- and mid-facial anatomies and the mandible; (2...up to 20 cm), nerve, vessels, muscle, tendon, ligament, and skin. Musculoskeletal /extrem­ ity injuries are present in more than 80% of all combat

  12. Armed Forces Institute of Regenerative Medicine Annual Report 2011

    DTIC Science & Technology

    2012-01-01

    4.4.3a, RCCC: Functional Scaffold for Musculoskeletal Repair and Delivery of Therapeutic Agents ......... 68 Project 4.4.3b, RCCC: Functional...scaffold is made of an anatomi - cally designed, fiber-reinforced scaffold and a collagen-based extracellular matrix similar to the native meniscus. The...cm), nerve, vessel, muscle, tendon, ligament, and skin. Musculoskeletal /extremity injuries are present in more than 80% of all combat injuries

  13. ECM and ECM-like materials - Biomaterials for applications in regenerative medicine and cancer therapy.

    PubMed

    Hinderer, Svenja; Layland, Shannon Lee; Schenke-Layland, Katja

    2016-02-01

    Regenerative strategies such as stem cell-based therapies and tissue engineering applications are being developed with the aim to replace, remodel, regenerate or support damaged tissues and organs. In addition to careful cell type selection, the design of appropriate three-dimensional (3D) scaffolds is essential for the generation of bio-inspired replacement tissues. Such scaffolds are usually made of degradable or non-degradable biomaterials and can serve as cell or drug carriers. The development of more effective and efficient drug carrier systems is also highly relevant for novel cancer treatment strategies. In this review, we provide a summary of current approaches that employ ECM and ECM-like materials, or ECM-synthetic polymer hybrids, as biomaterials in the field of regenerative medicine. We further discuss the utilization of such materials for cell and drug delivery, and highlight strategies for their use as vehicles for cancer therapy.

  14. Horse hair follicles: A novel dermal stem cell source for equine regenerative medicine.

    PubMed

    Michler, Jule K; Hillmann, Aline; Savkovic, Vuk; Mülling, Christoph K W

    2017-09-02

    The easily accessible niche represented by skin and its appendages may serve as a promising source to complement modern regenerative medicine for horses. In humans and in animal models for human medicine, the hair follicle and its stem cell niches are well characterized. Since literature in this field of equine research is scarce, we sought to analyze cells of the dermal stem cell niche of the equine hair follicle morphologically and for a subset of markers useful for cell characterization via immunolabeling. We cultured equine forelock skin explants to obtain cultures with cells migrating from the hair follicles. Isolation of cells revealed typical fibroblast morphology with a strong tendency to aggregate and form spheroids. For immunofluorescent characterization of primary isolations, we tested an antibody panel consisting of lineage makers for the dermal compartment of the hair follicle, markers associated with an undifferentiated cell status and markers for epithelial cell types as negative controls. All antibodies used were also tested on equine skin sections. The isolated cells displayed clear profiles of dermal and undifferentiated cells. To substantiate our findings, we tested our primary isolations for established equine multipotent mesenchymal stromal cell antigen expression markers in flow cytometry experiments yielding strong convergence. The data presented here provide insights to a stem cell source in horses almost unnoticed to date. The basic investigations of the equine dermal hair follicle stem cell niche confirm the expression of standard markers used in other species and lay the foundation for future studies on this easily available adult stem cell source. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  15. Macroporous thin membranes for cell transplant in regenerative medicine.

    PubMed

    Antolinos-Turpín, C M; Morales Román, R M; Rodenas-Rochina, J; Gómez Ribelles, J L; Gómez-Tejedor, J A

    2015-10-01

    The aim of this paper is to present a method to produce macroporous thin membranes made of poly (ethyl acrylate-co-hydroxyethyl acrylate) copolymer network with varying cross-linking density for cell transplantation and prosthesis fabrication. The manufacture process is based on template techniques and anisotropic pore collapse. Pore collapse was produced by swelling the membrane in acetone and subsequently drying and changing the solvent by water to produce 100 microns thick porous membranes. These very thin membranes are porous enough to hold cells to be transplanted to the organism or to be colonized by ingrowth from neighboring tissues in the organism, and they present sufficient tearing stress to be sutured with surgical thread. The obtained pore morphology was observed by Scanning Electron Microscope, and confocal laser microscopy. Mechanical properties were characterized by stress-strain experiments in tension and tearing strength measurements. Morphology and mechanical properties were related to the different initial thickness of the scaffold and the cross-linking density of the polymer network. Seeding efficiency and proliferation of mesenchymal stem cells inside the pore structure were determined at 2 h, 1, 7, 14 and 21 days from seeding. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. New cell engineering approaches for cartilage regenerative medicine.

    PubMed

    Cucchiarini, Magali

    2017-01-01

    Articular cartilage injuries have an inadequate aptitude to reproduce the original structure and functions of this highly specialized tissue. As most of the currently available options also do not lead to the restoration of the original hyaline cartilage, novel treatments are critically needed to address this global problems in the clinics. Gene therapy combined with tissue engineering approaches offers effective tools capable of enhancing cartilage repair experimentally, especially those based on the controlled delivery of the highly effective, clinically adapted recombinant adeno-associated viral (rAAV) vectors. This work presents an overview of the most recent evidence showing the benefits of using rAAV vectors and biocompatible materials for the elaboration of adapted treatments against cartilage injuries.

  17. Magnetically Targeted Stem Cell Delivery for Regenerative Medicine

    PubMed Central

    Cores, Jhon; Caranasos, Thomas G.; Cheng, Ke

    2015-01-01

    Stem cells play a special role in the body as agents of self-renewal and auto-reparation for tissues and organs. Stem cell therapies represent a promising alternative strategy to regenerate damaged tissue when natural repairing and conventional pharmacological intervention fail to do so. A fundamental impediment for the evolution of stem cell therapies has been the difficulty of effectively targeting administered stem cells to the disease foci. Biocompatible magnetically responsive nanoparticles are being utilized for the targeted delivery of stem cells in order to enhance their retention in the desired treatment site. This noninvasive treatment-localization strategy has shown promising results and has the potential to mitigate the problem of poor long-term stem cell engraftment in a number of organ systems post-delivery. In addition, these same nanoparticles can be used to track and monitor the cells in vivo, using magnetic resonance imaging. In the present review we underline the principles of magnetic targeting for stem cell delivery, with a look at the logic behind magnetic nanoparticle systems, their manufacturing and design variants, and their applications in various pathological models. PMID:26133387

  18. Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine

    PubMed Central

    Camacho-Morales, Alberto

    2016-01-01

    Research on mesenchymal stem cells (MSCs) continues to progress rapidly. Nevertheless, the field faces several challenges, such as inherent cell heterogeneity and the absence of unique MSCs markers. Due to MSCs' ability to differentiate into multiple tissues, these cells represent a promising tool for new cell-based therapies. However, for tissue engineering applications, it is critical to start with a well-defined cell population. Additionally, evidence that MSCs subpopulations may also feature distinct characteristics and regeneration potential has arisen. In this report, we present an overview of the identification of MSCs based on the expression of several surface markers and their current tissue sources. We review the use of MSCs subpopulations in recent years and the main methodologies that have addressed their isolation, and we emphasize the most-used surface markers for selection, isolation, and characterization. Next, we discuss the osteogenic and chondrogenic differentiation from MSCs subpopulations. We conclude that MSCs subpopulation selection is not a minor concern because each subpopulation has particular potential for promoting the differentiation into osteoblasts and chondrocytes. The accurate selection of the subpopulation advances possibilities suitable for preclinical and clinical studies and determines the safest and most efficacious regeneration process. PMID:27725838

  19. Adult stem cells: hopes and hypes of regenerative medicine.

    PubMed

    Dulak, Józef; Szade, Krzysztof; Szade, Agata; Nowak, Witold; Józkowicz, Alicja

    2015-01-01

    Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells in a specific tissue. Unipotent cells differentiate only into one cell type, like e.g. satellite cells of skeletal muscle. There are many examples of successful clinical applications of stem cells. Over million patients worldwide have benefited from bone marrow transplantations performed for treatment of leukemias, anemias or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially the patient-specific iPSC, have a tremendous therapeutic potential, but their clinical application will require overcoming numerous drawbacks. Therefore, the use of adult stem cells, which are multipotent or unipotent, can be at present a more achievable strategy. Noteworthy, some studies ascribed particular adult stem cells as pluripotent. However, despite efforts, the postulated pluripotency of such events like "spore-like cells", "very small embryonic-like stem cells" or "multipotent adult progenitor cells" have not been confirmed in stringent independent studies. Also plasticity of the bone marrow-derived cells which were suggested to differentiate e.g. into cardiomyocytes, has not been positively verified, and their therapeutic effect, if observed, results rather from the paracrine activity. Here we discuss the examples of recent studies on adult stem cells in the light of current understanding of stem cell biology.

  20. Polymer biomaterial constructs for regenerative medicine and functional biological systems

    NASA Astrophysics Data System (ADS)

    Meng, Linghui

    The use of collagen as a biomaterial is currently undergoing a renaissance in the tissue engineering field. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenicity, make collagen a primary material resource in medical applications. Described herein is work towards the development of novel collagen-based matrices, with additional multi-functionality imparted through a novel in-situ crosslinking approach. The process of electrospinning has become a widely used technique for the creation of fibrous scaffolds for tissue engineering applications due to its ability to rapidly create structures composed of nano-scale polymer fibers closely resembling the architecture of the extracellular matrix (ECM). Collagen-PCL sheath-core bicomponent fibrous scaffolds were fabricated using a novel variation on traditional electrospinning, known as co-axial electrospinning. The results showed that the addition of a synthetic polymer core into collagen nanofibers remarkably increased the mechanical strength of collagen matrices spun from the benign solvent system. A novel single-step, in-situ collagen crosslink approach was developed in order to solve the problems dominating traditional collagen crosslinking methods, such as dimensional shrinking and loss of porous morphology, and to simplify the crosslinking procedure for electrospun collagen scaffolds. The excess amount of NHS present in the crosslinking mixture was found to delay the EDC/collagen coupling reaction in a controlled fashion. Fundamental investigations into the development and characterization of in-situ crosslinked collagen matrices such as fibrous scaffolds, gels and sponges, as well as their biomedical applications including cell culture substrates, wound dressings, drug delivery matrices and bone regeneration substitutes, were performed. The preliminary mice studies indicated that the in-situ crosslinked collagen matrices could be good candidates

  1. Regenerative medicine technology applied to gastroenterology: current status and future perspectives.

    PubMed

    Orlando, Giuseppe

    2012-12-21

    This special issue of World Journal of Gastroenterology has been conceived to illustrate to gastroenterology operators the role that regenerative medicine (RM) will have in the progress of gastrointestinal (GI) medicine. RM is a multidisciplinary field aiming to replace, regenerate or repair diseased tissues or organs. The past decade has been marked by numerous ground-breaking achievements that led experts in the field to manufacture functional substitutes of relatively simple organs. This progress is paving the ground for investigations that aims to the bioengineering and regeneration of more complex organs like livers, pancreas and intestine. In this special issue, the reader will be introduced, hand-in-hand, to explore the field of RM and will be educated on the progress, pitfalls and promise of RM technologies as applied to GI medicine.

  2. Intra-articular Treatment of Knee Osteoarthritis: from Anti-inflammatories to Products of Regenerative Medicine

    PubMed Central

    Richards, Masters M.; Maxwell, Joshua Shane; Weng, Lihui; Angelos, Mathew G.; Golzarian, Jafar

    2016-01-01

    Objectives Knee osteoarthritis (OA)1 is a debilitating condition that may ultimately require total knee arthroplasty (TKA)2. Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI)3. The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment. Methods A literature search was executed using Medline, Cochrane, and Embase with keywords ”knee osteoarthritis” and “injection.” Specifically, articles discussing intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP)4 and mesenchymal stem cells (MSC)5, were analyzed. Results Forty-five publications were scrutinized. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5. Papers included animal models. Local anesthetics have potential side effects and may only be effective for four hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to one months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation. Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint. Conclusions Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they

  3. Induced pluripotent stem cells and their use in cardiac and neural regenerative medicine.

    PubMed

    Skalova, Stepanka; Svadlakova, Tereza; Shaikh Qureshi, Wasay Mohiuddin; Dev, Kapil; Mokry, Jaroslav

    2015-02-13

    Stem cells are unique pools of cells that are crucial for embryonic development and maintenance of adult tissue homeostasis. The landmark Nobel Prize winning research by Yamanaka and colleagues to induce pluripotency in somatic cells has reshaped the field of stem cell research. The complications related to the usage of pluripotent embryonic stem cells (ESCs) in human medicine, particularly ESC isolation and histoincompatibility were bypassed with induced pluripotent stem cell (iPSC) technology. The human iPSCs can be used for studying embryogenesis, disease modeling, drug testing and regenerative medicine. iPSCs can be diverted to different cell lineages using small molecules and growth factors. In this review we have focused on iPSC differentiation towards cardiac and neuronal lineages. Moreover, we deal with the use of iPSCs in regenerative medicine and modeling diseases like myocardial infarction, Timothy syndrome, dilated cardiomyopathy, Parkinson's, Alzheimer's and Huntington's disease. Despite the promising potential of iPSCs, genome contamination and low efficacy of cell reprogramming remain significant challenges.

  4. Plasticity of male germline stem cells and their applications in reproductive and regenerative medicine.

    PubMed

    Chen, Zheng; Li, Zheng; He, Zuping

    2015-01-01

    Spermatogonial stem cells (SSCs), also known as male germline stem cells, are a small subpopulation of type A spermatogonia with the potential of self-renewal to maintain stem cell pool and differentiation into spermatids in mammalian testis. SSCs are previously regarded as the unipotent stem cells since they can only give rise to sperm within the seminiferous tubules. However, this concept has recently been challenged because numerous studies have demonstrated that SSCs cultured with growth factors can acquire pluripotency to become embryonic stem-like cells. The in vivo and in vitro studies from peers and us have clearly revealed that SSCs can directly transdifferentiate into morphologic, phenotypic, and functional cells of other lineages. Direct conversion to the cells of other tissues has important significance for regenerative medicine. SSCs from azoospermia patients could be induced to differentiate into spermatids with fertilization and developmental potentials. As such, SSCs could have significant applications in both reproductive and regenerative medicine due to their unique and great potentials. In this review, we address the important plasticity of SSCs, with focuses on their self-renewal, differentiation, dedifferentiation, transdifferentiation, and translational medicine studies.

  5. Shen-Jing as a Chinese medicine concept might be a counterpart of stem cells in regenerative medicine.

    PubMed

    Ren, Yan-Bo; Huang, Jian-Hua; Cai, Wai-Jiao; Shen, Zi-Yin

    2015-07-04

    As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.

  6. Peroxisome Proliferator-Activated Receptor (PPAR) in Regenerative Medicine: Molecular Mechanism for PPAR in Stem Cells' Adipocyte Differentiation.

    PubMed

    Xie, Qiang; Tian, Taoran; Chen, Zhaozhao; Deng, Shuwen; Sun, Ke; Xie, Jing; Cai, Xiaoxiao

    2016-01-01

    Regenerative medicine plays an indispensable role in modern medicine and many trials and researches have therefore been developed to fit our medical needs. Tissue engineering has proven that adipose tissue can widely be used and brings advantages to regenerative medicine. Moreover, a trait of adipose stem cells being isolated and grown in vitro is a cornerstone to various applications. Since the adipose tissue has been widely used in regenerative medicine, numerous studies have been conducted to seek methods for gaining more adipocytes. To investigate molecular mechanism for adipocyte differentiation, peroxisome proliferator-activated receptor (PPAR) has been widely studied to find out its functional mechanism, as a key factor for adipocyte differentiation. However, the precise molecular mechanism is still unknown. This review thus summarizes recent progress on the study of molecular mechanism and role of PPAR in adipocyte differentiation.

  7. [Neonatal medicine, past and present].

    PubMed

    Salle, Bernard L; Vert, Paul

    2013-06-01

    This review deals with early neonatal medicine and its rapid development as a medical specialty, starting with the birth of neonatology in the early 19th century. Shaffer first used the term neonatology in 1963 to cover neonatal disorders and their treatment. Between the early 19th century and the 1950s, neonatal care was ensured by obstetricians, whose main goal was to reduce neonatal mortality. After the second world war, and especially the 1960s, the development of neonatal physiology and pathophysiology provided insights into neonatal diseases and their treatment, including respiratory distress, jaundice, malnutrition, and prevention of respiratory distress and brain complications, etc. Currently, neonatal mortality, regardless of birth weight, is below 2/1000, and the survival rate of premature infants, regardless of gestational age and birth weight, exceeds 85%. This represents a resounding success, despite the associated costs, ethical issues, and inevitable morbidity.

  8. Therapeutic application of mesenchymal stem cell-derived exosomes: A promising cell-free therapeutic strategy in regenerative medicine.

    PubMed

    Motavaf, M; Pakravan, K; Babashah, S; Malekvandfard, F; Masoumi, M; Sadeghizadeh, M

    2016-06-30

    Mesenchymal stem cells have emerged as promising therapeutic candidates in regenerative medicine. The mechanisms underlying mesenchymal stem cells regenerative properties were initially attributed to their engraftment in injured tissues and their subsequent transdifferentiation to repair and replace damaged cells. However, studies in animal models and patients indicated that the low number of transplanted mesenchymal stem cells localize to the target tissue and transdifferentiate to appropriate cell lineage. Instead the regenerative potential of mesenchymal stem cells has been found - at least in part - to be mediated via their paracrine actions. Recently, a secreted group of vesicles, called "exosome" has been identified as major mediator of mesenchymal stem cells therapeutic efficacy. In this review, we will summarize the current literature on administration of exosomes released by mesenchymal stem cells in regenerative medicine and suggest how they could help to improve tissue regeneration following injury.

  9. The role of regenerative medicine in the treatment of sports injuries.

    PubMed

    Malanga, Gerard; Nakamura, Reina; Nakamurra, Reina

    2014-11-01

    Traditional treatment of sports injuries includes use of the PRICE principle (Protection, Rest, Ice, Compression, Elevation), nonsteroidal anti-inflammatories, physical therapy modalities, and corticosteroid injections. Recent evidence has raised concerns over this traditional treatment approach regarding the use of anti-inflammatories and injectable corticosteroids. More recent treatments, known as regenerative medicine, include platelet-rich plasma and stem cell therapies. Evidence for their efficacy in a variety of sports injuries has emerged, ranging from tendinopathy and muscle tears to ligament and chondral injuries. This article reviews the literature regarding established treatments for sports injuries and these more innovative treatments.

  10. Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans

    PubMed Central

    Arora, Pooja; Sindhu, Annu; Dilbaghi, Neeraj; Chaudhury, Ashok; Rajakumar, Govindasamy; Rahuman, Abdul Abdul

    2012-01-01

    Nanotechnology is a fast growing area of research that aims to create nanomaterials or nanostructures development in stem cell and tissue-based therapies. Concepts and discoveries from the fields of bio nano research provide exciting opportunities of using stem cells for regeneration of tissues and organs. The application of nanotechnology to stem-cell biology would be able to address the challenges of disease therapeutics. This review covers the potential of nanotechnology approaches towards regenerative medicine. Furthermore, it focuses on current aspects of stem- and tissue-cell engineering. The magnetic nanoparticles-based applications in stem-cell research open new frontiers in cell and tissue engineering. PMID:22260258

  11. Signaling pathways in osteogenesis and osteoclastogenesis: Lessons from cranial sutures and applications to regenerative medicine

    PubMed Central

    Maxhimer, Justin B.; Bradley, James P.; Lee, Justine C.

    2015-01-01

    One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial bones. Although only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances, the molecular mechanisms elucidated from these studies have provided basic knowledge of bone homeostasis. This work has translated to methods and advances in bone tissue engineering. In this review, we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine. PMID:25961069

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

    PubMed Central

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

    2015-01-01

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

  13. The emerging landscape of reimbursement of regenerative medicine products in the UK: publications, policies and politics.

    PubMed

    Mahalatchimy, Aurélie; Faulkner, Alex

    2017-10-03

    This paper aims to map the trends and analyze key institutional dynamics that constitute the policies for reimbursement of regenerative medicine (RM), especially in the UK. Two quantitative publications studies using Google Scholar and a qualitative study based on a larger study of 43 semi-structured interviews. Reimbursement has been a growing topic of publications specific to RM and independent from orphan drugs. Risk-sharing schemes receive attention among others for dealing with RM reimbursement. Trade organizations have been especially involved on RM reimbursement issues and have proposed solutions. The policy and institutional landscape of reimbursement studies in RM is a highly variegated and conflictual one and in its infancy.

  14. Next-generation regenerative medicine: organogenesis from stem cells in 3D culture.

    PubMed

    Sasai, Yoshiki

    2013-05-02

    The behavior of stem cells, when they work collectively, can be much more sophisticated than one might expect from their individual programming. This Perspective covers recent discoveries about the dynamic patterning and structural self-formation of complex organ buds in 3D stem cell culture, including the generation of various neuroectodermal and endodermal tissues. For some tissues, epithelial-mesenchymal interactions can also be manipulated in coculture to guide organogenesis. This new area of stem cell research-the spatiotemporal control of dynamic cellular interactions-will open a new avenue for next-generation regenerative medicine.

  15. Metabolomics: a valuable tool for stem cell monitoring in regenerative medicine

    PubMed Central

    McNamara, Laura E.; Sjöström, Terje; Meek, R. M. Dominic; Oreffo, Richard O. C.; Su, Bo; Dalby, Matthew J.; Burgess, Karl E. V.

    2012-01-01

    Metabolomics is a method for investigation of changes in the global metabolite profile of cells. This paper discusses the technical application of the approach, considering metabolite extraction, separation, mass spectrometry and data interpretation. A particular focus is on the application of metabolomics to the study of stem cell physiology in the context of biomaterials and regenerative medicine. Case studies are used to illustrate key points, focusing on the use of metabolomics in the examination of mesenchymal stem cell responses to titania-nanopillared substrata designed for orthopaedic applications. PMID:22628210

  16. Tissue engineering and regenerative medicine in basic research: a year in review of 2014.

    PubMed

    Huang, Jia; Lin, Xunxun; Shi, Yuan; Liu, Wei

    2015-04-01

    Tissue engineering and regenerative medicine (TERM) remains to be one of the fastest growing fields, which covers a wide scope of topics of both basic and applied biological researches. This overview article summarized the advancements in basic researches of TERM area, including stem cell biology, cell engineering, somatic nuclear transfer, genomic editing, discovery of new tissue progenitor/stem cells, and immunomodulation of stem cells and tissue regeneration. It reflects the cutting-edge achievements in basic researches, which will lay solid scientific foundation for future TERM translational researches.

  17. Regenerative Medicine for the Heart: Perspectives on Stem-Cell Therapy

    PubMed Central

    Cho, Gun-Sik; Fernandez, Laviel

    2014-01-01

    Abstract Significance: Despite decades of progress in cardiovascular biology and medicine, heart disease remains the leading cause of death, and there is no cure for the failing heart. Since heart failure is mostly caused by loss or dysfunction of cardiomyocytes (CMs), replacing dead or damaged CMs with new CMs might be an ideal way to reverse the disease. However, the adult heart is composed mainly of terminally differentiated CMs that have no significant self-regeneration capacity. Recent Advances: Stem cells have tremendous regenerative potential and, thus, current cardiac regenerative research has focused on developing stem cell sources to repair damaged myocardium. Critical Issues: In this review, we examine the potential sources of cells that could be used for heart therapies, including embryonic stem cells and induced pluripotent stem cells, as well as alternative methods for activating the endogenous regenerative mechanisms of the heart via transdifferentiation and cell reprogramming. We also discuss the current state of knowledge of cell purification, delivery, and retention. Future Directions: Efforts are underway to improve the current stem cell strategies and methodologies, which will accelerate the development of innovative stem-cell therapies for heart regeneration. Antioxid. Redox Signal. 21, 2018–2031. PMID:25133793

  18. Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

    PubMed Central

    Sundelacruz, Sarah; Kaplan, David L.

    2009-01-01

    In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

  19. Cell-fusion-mediated reprogramming: pluripotency or transdifferentiation? Implications for regenerative medicine.

    PubMed

    Sanges, Daniela; Lluis, Frederic; Cosma, Maria Pia

    2011-01-01

    Cell-cell fusion is a natural process that occurs not only during development, but as has emerged over the last few years, also with an important role in tissue regeneration. Interestingly, in-vitro studies have revealed that after fusion of two different cell types, the developmental potential of these cells can change. This suggests that the mechanisms by which cells differentiate during development to acquire their identities is not irreversible, as was considered until a few years ago. To date, it is well established that the fate of a cell can be changed by a process known as reprogramming. This mainly occurs in two different ways: the differentiated state of a cell can be reversed back into a pluripotent state (pluripotent reprogramming), or it can be switched directly to a different differentiated state (lineage reprogramming). In both cases, these possibilities of obtaining sources of autologous somatic cells to maintain, replace or rescue different tissues has provided new and fundamental insights in the stem-cell-therapy field. Most interestingly, the concept that cell reprogramming can also occur in vivo by spontaneous cell fusion events is also emerging, which suggests that this mechanism can be implicated not only in cellular plasticity, but also in tissue regeneration. In this chapter, we will summarize the present knowledge of the molecular mechanisms that mediate the restoration of pluripotency in vitro through cell fusion, as well as the studies carried out over the last 3 decades on lineage reprogramming, both in vitro and in vivo. How the outcome of these studies relate to regenerative medicine applications will also be discussed.

  20. Back to the future: how human induced pluripotent stem cells will transform regenerative medicine

    PubMed Central

    Svendsen, Clive N.

    2013-01-01

    Based on cloning studies in mammals, all adult human cells theoretically contain DNA that is capable of creating a whole new person. Cells are maintained in their differentiated state by selectively activating some genes and silencing. The dogma until recently was that cell differentiation was largely fixed unless exposed to the environment of an activated oocyte. However, it is now possible to activate primitive pluripotent genes within adult human cells that take them back in time to a pluripotent state (termed induced pluripotent stem cells). This technology has grown at an exponential rate over the past few years, culminating in the Nobel Prize in medicine. Discussed here are recent developments in the field as they relate to regenerative medicine, with an emphasis on creating functional cells, editing their genome, autologous transplantation and how this ground-breaking field may eventually impact human aging. PMID:23945396

  1. Opening the gateways to market and adoption of regenerative medicine? The UK case in context.

    PubMed

    Faulkner, Alex

    2016-04-01

    Regenerative medicine is a site for opposing forces of gatekeeping and innovation. This applies both to regulation of market entry and to clinical adoption. Key gateways include the EU's Advanced Therapy Medicinal Products Regulation, technology assessment body NICE and commissioning/service contractor National Health Service England. The paper maps recent gatekeeping flexibilities, describing the range of gateways to market and healthcare adoption seen as alternatives to mainstream routes. The initiatives range from exemptions in pharmaceutical and ATMP regulations, through 'adaptive pathways' and 'risk-based' approaches, to special designation for promising innovation, value-based assessment and commissioner developments. Future developments are considered in the UK's 'accelerated access review'. Caution is urged in assessing the impact of these gateway flexibilities and their market and public health implications.

  2. [Current status and perspective on regenerative medicine for spinal cord injury using iPS cell].

    PubMed

    Nakamura, Masaya; Toyama, Yoshiaki; Okano, Hideyuki

    2013-01-01

    Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya Yamanaka and Sir John Gurdon, there is an increasing interest in the iPS cells and reprogramming technologies in medical science. While iPS cells are expected to open new era providing enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine, safety-related concerns for iPS cell-based cell therapy should be resolved prior to the clinical application of iPS cells. In this symposium, the pre-clinical investigations of cell therapy for SCI using neural stem/progenitor cells derived from iPS cells, and their safety issues in vivo are outlined.

  3. Multifunctional quantum dots-based cancer diagnostics and stem cell therapeutics for regenerative medicine.

    PubMed

    Onoshima, Daisuke; Yukawa, Hiroshi; Baba, Yoshinobu

    2015-12-01

    A field of recent diagnostics and therapeutics has been advanced with quantum dots (QDs). QDs have developed into new formats of biomolecular sensing to push the limits of detection in biology and medicine. QDs can be also utilized as bio-probes or labels for biological imaging of living cells and tissues. More recently, QDs has been demonstrated to construct a multifunctional nanoplatform, where the QDs serve not only as an imaging agent, but also a nanoscaffold for diagnostic and therapeutic modalities. This review highlights the promising applications of multi-functionalized QDs as advanced nanosensors for diagnosing cancer and as innovative fluorescence probes for in vitro or in vivo stem cell imaging in regenerative medicine.

  4. Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration.

    PubMed

    Kraus, Petra; Lufkin, Thomas

    2017-01-01

    The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 10(13) cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones. One area receiving attention is regeneration of the intervertebral discs (IVDs), which are located between the vertebrae and function to give flexibility and support load to the spine. Degenerated discs are a major cause of lower back pain. Different stem cell based regenerative medicine approaches to cure disc degeneration are now available, including using autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and even attempts at direct transdifferentiation of somatic cells. Here we discuss some of the recent advances, successes, drawbacks, and the failures of the above-mentioned approaches.

  5. Cell- and gene-based therapeutic strategies for periodontal regenerative medicine.

    PubMed

    Rios, Hector F; Lin, Zhao; Oh, Bina; Park, Chan Ho; Giannobile, William V

    2011-09-01

    Inflammatory periodontal diseases are a leading cause of tooth loss and are linked to multiple systemic conditions, such as cardiovascular disease and stroke. Reconstruction of the support and function of affected tooth-supporting tissues represents an important therapeutic endpoint for periodontal regenerative medicine. An improved understanding of periodontal biology coupled with current advances in scaffolding matrices has introduced novel treatments that use cell and gene therapy to enhance periodontal tissue reconstruction and its biomechanical integration. Cell and gene delivery technologies have the potential to overcome limitations associated with existing periodontal therapies, and may provide a new direction in sustainable inflammation control and more predictable tissue regeneration of supporting alveolar bone, periodontal ligament, and cementum. This review provides clinicians with the current status of these early-stage and emerging cell- and gene-based therapeutics in periodontal regenerative medicine, and introduces their future application in clinical periodontal treatment. The paper concludes with prospects on the application of cell and gene tissue engineering technologies for reconstructive periodontology.

  6. Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

    PubMed Central

    Kraus, Petra; Lufkin, Thomas

    2017-01-01

    The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 1013 cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones. One area receiving attention is regeneration of the intervertebral discs (IVDs), which are located between the vertebrae and function to give flexibility and support load to the spine. Degenerated discs are a major cause of lower back pain. Different stem cell based regenerative medicine approaches to cure disc degeneration are now available, including using autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and even attempts at direct transdifferentiation of somatic cells. Here we discuss some of the recent advances, successes, drawbacks, and the failures of the above-mentioned approaches. PMID:28326305

  7. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine.

    PubMed

    Hinderer, Svenja; Brauchle, Eva; Schenke-Layland, Katja

    2015-11-18

    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug-free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus-free vascular substitutes that are smaller than 6 mm, and stem cell-recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off-the-shelf biomaterials as well as automatable and up-scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact- and marker-free biomaterial and extracellular matrix assessment methods are highlighted.

  8. Human Term Placental Cells: Phenotype, Properties and New Avenues in Regenerative Medicine

    PubMed Central

    Caruso, Maddalena; Evangelista, Marco; Parolini, Ornella

    2012-01-01

    The human placenta has long been the subject of scientific interest due to the important roles which it performs during pregnancy in sustaining the fetus and maintaining fetomaternal tolerance. More recently, however, researchers have begun to investigate the possibility that the placenta’s utility may extend beyond fetal development to act as a source of cells with clinically relevant properties. Indeed, several groups have reported the isolation of cells from different placental regions which display both multilineage differentiation potential and immunomodulatory properties in vitro. Furthermore, these cells have also been shown to secrete soluble factors involved in pathophysiological processes that may aid tissue repair. Cells with such features will clearly find application in the field of regenerative medicine for the repair/regeneration of damaged or diseased tissues or organs. In line with these promising findings, several preclinical and clinical studies conducted to date argue in strong favor of the therapeutic utility of placenta-derived cells for the treatment of several diseases. Although much work remains to be conducted in order to fully understand the properties of placental cells and the mechanisms which underlie their beneficial effects in vivo, data reported to date nonetheless provide compelling evidence in support of the placenta as a cell source for use in regenerative medicine. PMID:24551761

  9. Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century

    PubMed Central

    Stoltz, J.-F.; de Isla, N.; Li, Y. P.; Bensoussan, D.; Zhang, L.; Huselstein, C.; Chen, Y.; Decot, V.; Magdalou, J.; Li, N.; Reppel, L.; He, Y.

    2015-01-01

    Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology, liver, ophthalmology, and organ's reconstruction). This review focuses mainly on tissue and organ regeneration using SC and in particular MSC. PMID:26300923

  10. Regenerative medicine, resource and regulation: lessons learned from the remedi project.

    PubMed

    Ginty, Patrick J; Rayment, Erin A; Hourd, Paul; Williams, David J

    2011-03-01

    The successful commercialization of regenerative medicine products provides a unique challenge to the manufacturer owing to a lack of suitable investment/business models and a constantly evolving regulatory framework. The resultant slow translation of scientific discovery into safe and clinically efficacious therapies is preventing many potential products from reaching the market. This is despite of the need for new therapies that may reduce the burden on the world's healthcare systems and address the desperate need for replacement tissues and organs. The collaborative Engineering and Physical Sciences Research Council (EPSRC)-funded remedi project was devised to take a holistic but manufacturing-led approach to the challenge of translational regenerative medicine in the UK. Through strategic collaborations and discussions with industry and other academic partners, many of the positive and negative issues surrounding business and regulatory success have been documented to provide a remedi-led perspective on the management of risk in business and the elucidation of the regulatory pathways, and how the two are inherently linked. This article represents the findings from these discussions with key stakeholders and the research into best business and regulatory practices.

  11. Priming adult stem cells by hypoxic pretreatments for applications in regenerative medicine.

    PubMed

    Muscari, Claudio; Giordano, Emanuele; Bonafè, Francesca; Govoni, Marco; Pasini, Alice; Guarnieri, Carlo

    2013-08-29

    The efficiency of regenerative medicine can be ameliorated by improving the biological performances of stem cells before their transplantation. Several ex-vivo protocols of non-damaging cell hypoxia have been demonstrated to significantly increase survival, proliferation and post-engraftment differentiation potential of stem cells. The best results for priming cultured stem cells against a following, otherwise lethal, ischemic stress have been obtained with brief intermittent episodes of hypoxia, or anoxia, and reoxygenation in accordance with the extraordinary protection afforded by the conventional maneuver of ischemic preconditioning in severely ischemic organs. These protocols of hypoxic preconditioning can be rather easily reproduced in a laboratory; however, more suitable pharmacological interventions inducing stem cell responses similar to those activated in hypoxia are considered among the most promising solutions for future applications in cell therapy. Here we want to offer an up-to-date review of the molecular mechanisms translating hypoxia into beneficial events for regenerative medicine. To this aim the involvement of epigenetic modifications, microRNAs, and oxidative stress, mainly activated by hypoxia inducible factors, will be discussed. Stem cell adaptation to their natural hypoxic microenvironments (niche) in healthy and neoplastic tissues will be also considered.

  12. Surface functionalization of nanobiomaterials for application in stem cell culture, tissue engineering, and regenerative medicine.

    PubMed

    Rana, Deepti; Ramasamy, Keerthana; Leena, Maria; Jiménez, Constanza; Campos, Javier; Ibarra, Paula; Haidar, Ziyad S; Ramalingam, Murugan

    2016-05-01

    Stem cell-based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial-based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell-based tissue engineering and regenerative medicine. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554-567, 2016.

  13. Applications and Implications of Heparin and Protamine in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Nemeno, Judee Grace E.; Lee, Kyung Mi

    2014-01-01

    Drug repositioning is one of the most rapidly emerging fields of study. This concept is anchored on the principle that diseases have similar damaged or affected signaling pathways. Recently, drugs have been repositioned not only for their alternative therapeutic uses but also for their applications as biomaterials in various fields. However, medical drugs as biomaterials are rarely focused on in reviews. Fragmin and protamine have been recently the sources of increasing attention in the field of tissue engineering and regenerative medicine. Fragmin and protamine have been manufactured primarily as a safe antidote for the circulating heparin. Lately, these drugs have been utilized as either micro- or nanoparticle biomaterials. In this paper, we will briefly describe the concept of drug repositioning and some of the medical drugs that have been repurposed for their alternative therapeutic uses. Also, this will feature the historical background of the studies focused on fragmin/protamine micro/nanoparticles (F/P M/NPs) and their applications as biomaterials in tissue engineering, stem cell therapy, and regenerative medicine. PMID:24995338

  14. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

    PubMed Central

    Hinderer, Svenja; Brauchle, Eva

    2015-01-01

    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

  15. Cell- and Gene-Based Therapeutic Strategies for Periodontal Regenerative Medicine

    PubMed Central

    Rios, Hector F.; Lin, Zhao; Oh, BiNa; Park, Chan Ho; Giannobile, William V.

    2012-01-01

    Inflammatory periodontal diseases are a leading cause of tooth loss and are linked to multiple systemic conditions, such as cardiovascular disease and stroke. Reconstruction of the support and function of affected tooth-supporting tissues represents an important therapeutic endpoint for periodontal regenerative medicine. An improved understanding of periodontal biology coupled with current advances in scaffolding matrices has introduced novel treatments that use cell and gene therapy to enhance periodontal tissue reconstruction and its biomechanical integration. Cell and gene delivery technologies have the potential to overcome limitations associated with existing periodontal therapies, and may provide a new direction in sustainable inflammation control and more predictable tissue regeneration of supporting alveolar bone, periodontal ligament, and cementum. This review provides clinicians with the current status of these early-stage and emerging cell- and gene-based therapeutics in periodontal regenerative medicine, and introduces their future application in clinical periodontal treatment. The paper concludes with prospects on the application of cell and gene tissue engineering technologies for reconstructive periodontology. PMID:21284553

  16. Tissue engineering and microRNAs: future perspectives in regenerative medicine.

    PubMed

    Gori, Manuele; Trombetta, Marcella; Santini, Daniele; Rainer, Alberto

    2015-01-01

    Tissue engineering is a growing area of biomedical research, holding great promise for a broad range of potential applications in the field of regenerative medicine. In recent decades, multiple tissue engineering strategies have been adopted to mimic and improve specific biological functions of tissues and organs, including biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems. MicroRNAs (miRNAs), noncoding small RNAs that negatively regulate the expression of downstream target mRNAs, are considered a novel class of molecular targets and therapeutics that may play an important role in tissue engineering. Herein, we highlight the latest achievements in regenerative medicine, focusing on the role of miRNAs as key modulators of gene expression, stem cell self-renewal, proliferation and differentiation, and eventually in driving cell fate decisions. Finally, we will discuss the contribution of miRNAs in regulating the rearrangement of the tissue microenvironment and angiogenesis, and the range of strategies for miRNA delivery into target cells and tissues. Manipulation of miRNAs is an alternative approach and an attractive strategy for controlling several aspects of tissue engineering, although some issues concerning their in vivo effects and optimal delivery methods still remain uncovered.

  17. Transportation of transplantable cell sheets fabricated with temperature-responsive culture surfaces for regenerative medicine.

    PubMed

    Nozaki, Takayuki; Yamato, Masayuki; Inuma, Toshiaki; Nishida, Kohji; Okano, Teruo

    2008-06-01

    Here we report transportation of cell sheets fabricated on temperature-responsive culture surfaces for regenerative medicine. On the surfaces cells adhere, spread and proliferate at 37 degrees C, but upon temperature reduction below 32 degrees C all the cells are spontaneously detached. When cells on the surfaces are challenged by long distance transportation, maintaining the temperature is critical. Therefore, we developed a portable homothermal container to keep the inner temperature at 36 degrees C for > 30 h without any need for batteries or energy supply. We transported and compared fibroblast sheets cultured on temperature-responsive surfaces in the container, at room temperature in a car, or on ice. After 8 h transportation by car, all cells at room temperature and on ice were detached from the surfaces and some were folded and broken into tiny pieces. On the other hand, fibroblast sheets transported in the container retained their adhesion to the dish surfaces and intact cell sheets were successfully harvested by temperature reduction. During the transportation, cell viability and histology were not impaired. This unique transportation device would be useful for cell sheet-based regenerative medicine utilizing temperature-responsive culture surfaces. Copyright (c) 2008 John Wiley & Sons, Ltd.

  18. Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century.

    PubMed

    Stoltz, J-F; de Isla, N; Li, Y P; Bensoussan, D; Zhang, L; Huselstein, C; Chen, Y; Decot, V; Magdalou, J; Li, N; Reppel, L; He, Y

    2015-01-01

    Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology, liver, ophthalmology, and organ's reconstruction). This review focuses mainly on tissue and organ regeneration using SC and in particular MSC.

  19. Human Pluripotent Stem Cell Mechanobiology: Manipulating the Biophysical Microenvironment for Regenerative Medicine and Tissue Engineering Applications.

    PubMed

    Ireland, Ronald G; Simmons, Craig A

    2015-11-01

    A stem cell in its microenvironment is subjected to a myriad of soluble chemical cues and mechanical forces that act in concert to orchestrate cell fate. Intuitively, many of these soluble and biophysical factors have been the focus of intense study to successfully influence and direct cell differentiation in vitro. Human pluripotent stem cells (hPSCs) have been of considerable interest in these studies due to their great promise for regenerative medicine. Culturing and directing differentiation of hPSCs, however, is currently extremely labor-intensive and lacks the efficiency required to generate large populations of clinical-grade cells. Improved efficiency may come from efforts to understand how the cell biophysical signals can complement biochemical signals to regulate cell pluripotency and direct differentiation. In this concise review, we explore hPSC mechanobiology and how the hPSC biophysical microenvironment can be manipulated to maintain and differentiate hPSCs into functional cell types for regenerative medicine and tissue engineering applications. © 2015 AlphaMed Press.

  20. Biocomposites reinforced by fibers or tubes as scaffolds for tissue engineering or regenerative medicine.

    PubMed

    Li, Xiaoming; Yang, Yu; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Watari, Fumio

    2014-05-01

    As a dynamic and hierarchically organized composite, native extracellular matrix (ECM) not only supplies mechanical support, which the embedded cells need, but also regulates various cellular activities through interaction with them. On the basis of the ECM-mimetic principle, good biocompatibility and appropriate mechanical properties are the two basic requirements that the ideal scaffolds for the tissue engineering or regenerative medicine need. Some fibers and tubes have been shown effective to reinforce scaffolds for tissue engineering or regenerative medicine. In this review, three parts, namely properties affected by the addition of fibers or tubes, scaffolds reinforced by fibers or tubes for soft tissue repair, and scaffolds reinforced by fibers or tubes for hard tissue repair are stated, which shows that tissue repair or regeneration efficacy was enhanced significantly by fiber or tube reinforcement. In addition, it indicates that these reinforcing agents can improve the biocompatibility and biodegradation of the scaffolds in most cases. However, there are still some concerns, such as the homogeneousness in structure or composition throughout the reinforced scaffolds, the adhesive strength between the matrix and the fibers or tubes, cytotoxicity of nanoscaled reinforcing agents, etc., which were also discussed in the conclusion and perspectives part. Copyright © 2013 Wiley Periodicals, Inc.

  1. Translating stem cell therapies: the role of companion animals in regenerative medicine

    PubMed Central

    Volk, Susan W.; Theoret, Christine

    2013-01-01

    Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell-based therapies involving hematopoietic (HSC) and mesenchymal stem cells (MSC) as well as other adult regenerative cells and recently embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC). In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the “One Health Initiative”, the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored. PMID:23627495

  2. Direct cellular reprogramming in Caenorhabditis elegans: facts, models, and promises for regenerative medicine.

    PubMed

    Zuryn, Steven; Daniele, Thomas; Jarriault, Sophie

    2012-01-01

    In vitro systems of cellular reprogramming [induced pluripotent stem (iPS) cells and direct reprogramming or transdifferentiation] are rapidly improving our repertoire of molecular techniques that can force cells in culture to change into a desired identity. However, the new frontier for regenerative medicine is in vivo cellular reprogramming, which in light of concerns about the safety of in vitro cell manipulations, is an increasingly attractive approach for regenerative medicine. Powerful in vivo approaches are currently being undertaken in the genetic model Caenorhabditis elegans. Several very distinct cell types have been induced to change or have been discovered to transform naturally, into altogether different cell types. These examples have improved our understanding of the fundamental molecular and cellular mechanisms that permit cell identity changes in live animals. In addition, the combination of a stereotyped lineage with single cell analyses allows dissection of the early and intermediate mechanisms of reprogramming, as well as their kinetics. As a result, several important concepts on in vivo cellular reprogramming have been recently developed.

  3. Canadians' support for radical life extension resulting from advances in regenerative medicine.

    PubMed

    Dragojlovic, Nick

    2013-04-01

    This paper explores Canadian public perceptions of a hypothetical scenario in which a radical increase in life expectancy results from advances in regenerative medicine. A national sample of 1231 adults completed an online questionnaire on stem cell research and regenerative medicine, including three items relating to the possibility of Canadians' average life expectancy increasing to 120 years by 2050. Overall, Canadians are strongly supportive of the prospect of extended lifespans, with 59% of the sample indicating a desire to live to 120 if scientific advances made it possible, and 47% of respondents agreeing that such increases in life expectancy are possible by 2050. The strongest predictors of support for radical life extension are individuals' general orientation towards science and technology and their evaluation of its plausibility. These results contrast with previous research, which has suggested public ambivalence for biomedical life extension, and point to the need for more research in this area. They suggest, moreover, that efforts to increase public awareness about anti-aging research are likely to increase support for the life-extending consequences of that research program.

  4. A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine

    PubMed Central

    Asuelime, Grace E.; Shi, Yanhong

    2012-01-01

    The field of regenerative medicine is rapidly gaining momentum as an increasing number of reports emerge concerning the induced conversions observed in cellular fate reprogramming. While in recent years, much attention has been focused on the conversion of fate-committed somatic cells to an embryonic-like or pluripotent state, there are still many limitations associated with the applications of induced pluripotent stem cell reprogramming, including relatively low reprogramming efficiency, the times required for the reprogramming event to take place, the epigenetic instability, and the tumorigenicity associated with the pluripotent state. On the other hand, lineage reprogramming involves the conversion from one mature cell type to another without undergoing conversion to an unstable intermediate. It provides an alternative approach in regenerative medicine that has a relatively lower risk of tumorigenesis and increased efficiency within specific cellular contexts. While lineage reprogramming provides exciting potential, there is still much to be assessed before this technology is ready to be applied in a clinical setting. PMID:22371436

  5. Emerging Applications of Stem Cell and Regenerative Medicine to Sports Injuries

    PubMed Central

    Ajibade, David A.; Vance, Danica D.; Hare, Joshua M.; Kaplan, Lee D.; Lesniak, Bryson P.

    2014-01-01

    Background: The treatment of sports-related musculoskeletal injuries with stem cells has become more publicized because of recent reports of high-profile athletes undergoing stem cell procedures. There has been increased interest in defining the parameters of safety and efficacy and the indications for potential use of stem cells in clinical practice. Purpose: To review the role of regenerative medicine in the treatment of sports-related injuries. Study Design: Review. Method: Relevant studies were identified through a PubMed search combining the terms stem cells and cartilage, ligament, tendon, muscle, and bone from January 2000 to August 2013. Studies and works cited in these studies were also reviewed. Results: Treatment of sports-related injuries with stem cells shows potential for clinical efficacy from the data available from basic science and animal studies. Conclusion: Cell-based therapies and regenerative medicine offer safe and potentially efficacious treatment for sports-related musculoskeletal injuries. Basic science and preclinical studies that support the possibility of enhanced recovery from sports injuries using cell-based therapies are accumulating; however, more clinical evidence is necessary to define the indications and parameters for their use. Accordingly, exposing patients to cell-based therapies could confer an unacceptable risk profile with minimal or no benefit. Continued clinical testing with animal models and clinical trials is necessary to determine the relative risks and benefits as well as the indications and methodology of treatment. PMID:26535296

  6. Syphilis: presentations in general medicine.

    PubMed

    Nyatsanza, Farai; Tipple, Craig

    2016-04-01

    Syphilis is caused by the spirochete bacteriumTreponema pallidumand can be transmitted both sexually and from mother to child.T pallidumcan infect any organ and produces a clinical disease with a relapsing and remitting course. It is not hard to see, therefore, why it is often described as the great mimic. In this review, we provide an update of modern syphilis epidemiology, clinical presentations, and testing and treatment strategies.

  7. Novel perspectives on the role of the human microbiota in regenerative medicine and surgery

    PubMed Central

    Pellegatta, Tommaso; Saler, Marco; Bonfanti, Viola; Nicoletti, Giovanni; Faga, Angela

    2016-01-01

    normal skin. Thus, the microbial environment may be considered as a potential tool in regenerative medicine and surgery. PMID:27882211

  8. Novel perspectives on the role of the human microbiota in regenerative medicine and surgery.

    PubMed

    Pellegatta, Tommaso; Saler, Marco; Bonfanti, Viola; Nicoletti, Giovanni; Faga, Angela

    2016-11-01

    normal skin. Thus, the microbial environment may be considered as a potential tool in regenerative medicine and surgery.

  9. Advances in using MRI probes and sensors for in vivo cell tracking as applied to regenerative medicine

    PubMed Central

    Srivastava, Amit K.; Kadayakkara, Deepak K.; Bar-Shir, Amnon; Gilad, Assaf A.; McMahon, Michael T.; Bulte, Jeff W. M.

    2015-01-01

    The field of molecular and cellular imaging allows molecules and cells to be visualized in vivo non-invasively. It has uses not only as a research tool but in clinical settings as well, for example in monitoring cell-based regenerative therapies, in which cells are transplanted to replace degenerating or damaged tissues, or to restore a physiological function. The success of such cell-based therapies depends on several critical issues, including the route and accuracy of cell transplantation, the fate of cells after transplantation, and the interaction of engrafted cells with the host microenvironment. To assess these issues, it is necessary to monitor transplanted cells non-invasively in real-time. Magnetic resonance imaging (MRI) is a tool uniquely suited to this task, given its ability to image deep inside tissue with high temporal resolution and sensitivity. Extraordinary efforts have recently been made to improve cellular MRI as applied to regenerative medicine, by developing more advanced contrast agents for use as probes and sensors. These advances enable the non-invasive monitoring of cell fate and, more recently, that of the different cellular functions of living cells, such as their enzymatic activity and gene expression, as well as their time point of cell death. We present here a review of recent advancements in the development of these probes and sensors, and of their functioning, applications and limitations. PMID:26035841

  10. Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor cells, and stem cell therapy.

    PubMed

    Maeshima, Akito; Nakasatomi, Masao; Nojima, Yoshihisa

    2014-01-01

    The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

  11. Regenerative medicine in kidney disease: where we stand and where to go.

    PubMed

    Borges, Fernanda T; Schor, Nestor

    2017-07-22

    The kidney is a complex organ with more than 20 types of specialized cells that play an important role in maintaining the body's homeostasis. The epithelial tubular cell is formed during embryonic development and has little proliferative capacity under physiological conditions, but after acute injury the kidney does have regenerative capacity. However, after repetitive or severe lesions, it may undergo a maladaptation process that predisposes it to chronic kidney injury. Regenerative medicine includes various repair and regeneration techniques, and these have gained increasing attention in the scientific literature. In the future, not only will these techniques contribute to the repair and regeneration of the human kidney, but probably also to the construction of an entire organ. New mechanisms studied for kidney regeneration and repair include circulating stem cells as mesenchymal stromal/stem cells and their paracrine mechanisms of action; renal progenitor stem cells; the leading role of tubular epithelial cells in the tubular repair process; the study of zebrafish larvae to understand the process of nephron development, kidney scaffold and its repopulation; and, finally, the development of organoids. This review elucidates where we are in terms of current scientific knowledge regarding these mechanisms and the promises of future scientific perspectives.

  12. The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications.

    PubMed

    Forostyak, Serhiy; Jendelova, Pavla; Sykova, Eva

    2013-12-01

    Diseases of the central nervous system still remain among the most challenging pathologies known to mankind, having no or limited therapeutic possibilities and a very pessimistic prognosis. Advances in stem cell biology in the last decade have shown that stem cells might provide an inexhaustible source of neurons and glia as well as exerting a neuroprotective effect on the host tissue, thus opening new horizons for tissue engineering and regenerative medicine. Here, we discuss the progress made in the cell-based therapy of spinal cord injury. An emphasis has been placed on the application of adult mesenchymal stromal cells (MSCs). We then review the latest and most significant results from in vitro and in vivo research focusing on the regenerative/neuroprotective properties of MSCs. We also attempt to correlate the effect of MSCs with the pathological events that are taking place in the nervous tissue after SCI. Finally, we discuss the results from preclinical and clinical trials involving different routes of MSC application into patients with neurological disorders of the spinal cord.

  13. The Powerful Functions of Peptide-Based Bioactive Matrices for Regenerative Medicine

    PubMed Central

    Rubert Pérez, Charles M.; Stephanopoulos, Nicholas; Sur, Shantanu; Lee, Sungsoo S.; Newcomb, Christina; Stupp, Samuel I.

    2014-01-01

    In an effort to develop bioactive matrices for regenerative medicine, peptides have been used widely to promote interactions with cells and elicit desired behaviors in vivo. This paper describes strategies that utilize peptide-based molecules as building blocks to create supramolecular nanostructures that emulate not only the architecture but also the chemistry of the extracellular matrix in mammalian biology. After initiating a desired regenerative response in vivo, the innate biodegradability of these systems allow for the natural biological processes to take over in order to promote formation of a new tissue without leaving a trace of the nonnatural components. These bioactive matrices can either bind or mimic growth factors or other protein ligands to elicit a cellular response, promote specific mechanobiological responses, and also guide the migration of cells with programmed directionality. In vivo applications discussed in this review using peptide-based matrices include the regeneration of axons after spinal cord injury, regeneration of bone, and the formation of blood vessels in ischemic muscle as a therapy in peripheral arterial disease and cardiovascular diseases. PMID:25366903

  14. The Interface of Functional Biotribology and Regenerative Medicine in Synovial Joints

    PubMed Central

    Komvopoulos, Kyriakos; Reddi, A. Hari

    2008-01-01

    Biotribology is the science of biological surfaces in sliding contact encompassing the concepts of friction, wear, and lubrication of interacting surfaces. This bioscience field has emerged from the classical field of tribology and is of paramount importance to the normal function of numerous tissues, including articular cartilage, blood vessels, heart, tendons, ligaments, and skin. Surprisingly, relatively little attention has been given to the restoration of surface characteristics in the fields of tissue engineering and regenerative medicine—the science of design and manufacture of new tissues for the functional restoration of impaired or diseased organs that depend on inductive signals, responding stem cells, and extracellular matrix scaffolding. Analogous to ancient civilizations (c. 3000 B.C.) that introduced wheeled vehicles, sledges for transporting heavy blocks, and lubricants, modern biotribologists must aim to restore surface characteristics to regenerated tissues and develop novel biomaterials with optimal tribological properties. The objective of this article is to highlight the significance of functional biotribology in the physiology of body surfaces and provide a comprehensive overview of unresolved issues and controversies as it relates to regenerative medicine. Specific attention is placed on the molecular basis of lubrication, mechanical and biochemical regulation of lubricating molecules, and the need to study wear processes in articular cartilage, especially in light of degenerative diseases, such as osteoarthritis. Surface engineering of replacement tissues exhibiting low friction and high wear resistance is examined using articular cartilage as an illustrative model system. PMID:18601586

  15. Papilla regeneration by injectable stem cell therapy with regenerative medicine: long-term clinical prognosis.

    PubMed

    Yamada, Yoichi; Nakamura, Sayaka; Ueda, Minoru; Ito, Kenji

    2015-03-01

    Black triangle (BT), an open interproximal space between teeth, can cause aesthetic concerns, food impaction, phonetic difficulties and periodontitis. The aim of this study was to determine the possibility and long-term prognosis of novel papilla regeneration with regenerative medicine, i.e. tissue-engineered papilla (TEP), and to investigate the potential of a tissue-engineering method for soft-tissue augmentation, especially aesthetic improvement of BT, with mesenchymal stem cells (MSCs) as the isolated cells, platelet-rich plasma (PRP) as the growth factor and hyaluronic acid (HA) as the scaffold. The parameters were assessed from a clinical point of view by measuring the distance from the tip of the interproximal papilla to the base of the contact area in each study region. The mean volumes, operation times and follow-up periods of TEP were 1.32 ± 0.25 ml, 2.2 ± 1.62 times and 55.3 ± 17.7 months; the mean improved BT values were 2.55 ± 0.89 mm. An aesthetic improvement was achieved. TEP was able to provide aesthetic improvement of black triangle and predictable results, and could emerge as another novel option for periodontal regenerative therapy in periodontal diseases. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Induced pluripotent stem cells in regenerative medicine: an argument for continued research on human embryonic stem cells.

    PubMed

    Lee, Han; Park, Jung; Forget, Bernard G; Gaines, Peter

    2009-09-01

    Human embryonic stem cells (ESCs) can be induced to differentiate into a wide range of tissues that soon could be used for therapeutic applications in regenerative medicine. Despite their developmental potential, sources used to generate human ESC lines raise serious ethical concerns, which recently prompted efforts to reprogram somatic cells back to a pluripotent state. These efforts resulted in the generation of induced pluripotent stem (iPS) cells that are functionally similar to ESCs. However, the genetic manipulations required to generate iPS cells may complicate their growth and developmental characteristics, which poses serious problems in predicting how they will behave when used for tissue-regenerative purposes. In this article we summarize the recently developed methodologies used to generate iPS cells, including those that minimize their genetic manipulation, and discuss several important complicating features of iPS cells that may compromise their future use for therapies in regenerative medicine.

  17. [Research progress of cell sheet technology and its applications in tissue engineering and regenerative medicine].

    PubMed

    Ma, Dongyang; Ren, Liling; Mao, Tianqiu

    2014-10-01

    Cell sheet engineering is an important technology to harvest the cultured cells in the form of confluent monolayers using a continuous culture method and a physical approach. Avoiding the use of enzymes, expended cells can be harvested together with endogenous extracellular matrix, cell-matrix contacts, and cell-cell contacts. With high efficiency of cell loading ability and without using exogenous scaffolds, cell sheet engineering has several advantages over traditional tissue engineering methods. In this article, we give an overview on cell sheet technology about its applications in the filed of tissue regeneration, including the construction of soft tissues (corneal, mucous membrane, myocardium, blood vessel, pancreas islet, liver, bladder and skin) and hard tissues (bone, cartilage and tooth root). This techonoly is promising to provide a novel strategy for the development of tissue engineering and regenerative medicine. And further works should be carried out on the operability of this technology and its feasibility to construct thick tissues.

  18. Hunt for pluripotent stem cell -- regenerative medicine search for almighty cell.

    PubMed

    Ratajczak, Mariusz Z; Zuba-Surma, Ewa K; Wysoczynski, Marcin; Wan, Wu; Ratajczak, Janina; Wojakowski, Wojciech; Kucia, Magda

    2008-05-01

    Regenerative medicine and tissue engineering are searching for a novel stem cell based therapeutic strategy that will allow for efficient treatment or even potential replacement of damaged organs. The pluripotent stem cell (PSC), which gives rise to cells from all three germ lineages, seems to be the most ideal candidate for such therapies. PSC could be extracted from developing embryos. However, since this source of stem cells for potential therapeutic purposes remains controversial, stem cell researchers look for PSC that could be isolated from the adult tissues or generated from already differentiated cells. True PSC should possess both potential for multilineage differentiation in vitro and, more importantly, also be able to complement in vivo blastocyst development. This review will summarize current approaches and limitations to isolate PSC from adult tissues or, alternatively, to generate it by nuclear reprogramming from already differentiated somatic cells.

  19. Concise review: parthenote stem cells for regenerative medicine: genetic, epigenetic, and developmental features.

    PubMed

    Daughtry, Brittany; Mitalipov, Shoukhrat

    2014-03-01

    Embryonic stem cells (ESCs) have the potential to provide unlimited cells and tissues for regenerative medicine. ESCs derived from fertilized embryos, however, will most likely be rejected by a patient's immune system unless appropriately immunomatched. Pluripotent stem cells (PSCs) genetically identical to a patient can now be established by reprogramming of somatic cells. However, practical applications of PSCs for personalized therapies are projected to be unfeasible because of the enormous cost and time required to produce clinical-grade cells for each patient. ESCs derived from parthenogenetic embryos (pESCs) that are homozygous for human leukocyte antigens may serve as an attractive alternative for immunomatched therapies for a large population of patients. In this study, we describe the biology and genetic nature of mammalian parthenogenesis and review potential advantages and limitations of pESCs for cell-based therapies.

  20. Hair follicle: a novel source of multipotent stem cells for tissue engineering and regenerative medicine.

    PubMed

    Mistriotis, Panagiotis; Andreadis, Stelios T

    2013-08-01

    The adult body harbors powerful reservoirs of stem cells that enable tissue regeneration under homeostatic conditions or in response to disease or injury. The hair follicle (HF) is a readily accessible mini organ within the skin and contains stem cells from diverse developmental origins that were shown to have surprisingly broad differentiation potential. In this review, we discuss the biology of the HF with particular emphasis on the various stem cell populations residing within the tissue. We summarize the existing knowledge on putative HF stem cell markers, the differentiation potential, and technologies to isolate and expand distinct stem cell populations. We also discuss the potential of HF stem cells for drug and gene delivery, tissue engineering, and regenerative medicine. We propose that the abundance of stem cells with broad differentiation potential and the ease of accessibility makes the HF an ideal source of stem cells for gene and cell therapies.

  1. Hair Follicle: A Novel Source of Multipotent Stem Cells for Tissue Engineering and Regenerative Medicine

    PubMed Central

    Mistriotis, Panagiotis

    2013-01-01

    The adult body harbors powerful reservoirs of stem cells that enable tissue regeneration under homeostatic conditions or in response to disease or injury. The hair follicle (HF) is a readily accessible mini organ within the skin and contains stem cells from diverse developmental origins that were shown to have surprisingly broad differentiation potential. In this review, we discuss the biology of the HF with particular emphasis on the various stem cell populations residing within the tissue. We summarize the existing knowledge on putative HF stem cell markers, the differentiation potential, and technologies to isolate and expand distinct stem cell populations. We also discuss the potential of HF stem cells for drug and gene delivery, tissue engineering, and regenerative medicine. We propose that the abundance of stem cells with broad differentiation potential and the ease of accessibility makes the HF an ideal source of stem cells for gene and cell therapies. PMID:23157470

  2. Artificial Cell Microencapsulated Stem Cells in Regenerative Medicine, Tissue Engineering and Cell Therapy

    PubMed Central

    Liu, Zun Chang; Chang, Thomas Ming Swi

    2012-01-01

    Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity of transdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo. PMID:20384219

  3. Adipose-Derived Stem Cells for Tissue Engineering and Regenerative Medicine Applications

    PubMed Central

    Dai, Ru; Wang, Zongjie; Samanipour, Roya; Koo, Kyo-in; Kim, Keekyoung

    2016-01-01

    Adipose-derived stem cells (ASCs) are a mesenchymal stem cell source with properties of self-renewal and multipotential differentiation. Compared to bone marrow-derived stem cells (BMSCs), ASCs can be derived from more sources and are harvested more easily. Three-dimensional (3D) tissue engineering scaffolds are better able to mimic the in vivo cellular microenvironment, which benefits the localization, attachment, proliferation, and differentiation of ASCs. Therefore, tissue-engineered ASCs are recognized as an attractive substitute for tissue and organ transplantation. In this paper, we review the characteristics of ASCs, as well as the biomaterials and tissue engineering methods used to proliferate and differentiate ASCs in a 3D environment. Clinical applications of tissue-engineered ASCs are also discussed to reveal the potential and feasibility of using tissue-engineered ASCs in regenerative medicine. PMID:27057174

  4. Reprogramming and transdifferentiation for cardiovascular development and regenerative medicine: where do we stand?

    PubMed Central

    Ebert, Antje D; Diecke, Sebastian; Chen, Ian Y; Wu, Joseph C

    2015-01-01

    Heart disease remains a leading cause of mortality and a major worldwide healthcare burden. Recent advances in stem cell biology have made it feasible to derive large quantities of cardiomyocytes for disease modeling, drug development, and regenerative medicine. The discoveries of reprogramming and transdifferentiation as novel biological processes have significantly contributed to this paradigm. This review surveys the means by which reprogramming and transdifferentiation can be employed to generate induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and induced cardiomyocytes (iCMs). The application of these patient-specific cardiomyocytes for both in vitro disease modeling and in vivo therapies for various cardiovascular diseases will also be discussed. We propose that, with additional refinement, human disease-specific cardiomyocytes will allow us to significantly advance the understanding of cardiovascular disease mechanisms and accelerate the development of novel therapeutic options. PMID:26183451

  5. Controlled assembly: a prerequisite for the use of recombinant spider silk in regenerative medicine?

    PubMed

    Rising, Anna

    2014-04-01

    Recent biotechnological progress has enabled the production of spider silk proteins, spidroins, in heterologous hosts. Matrices based on recombinant spidroins support stem cell growth and are well tolerated when implanted in living tissue, thus the material is highly attractive for use in regenerative medicine. However, the matrices made are far from natural silk in terms of mechanical properties and are either spontaneously assembled, which results in heterogeneous products, or spun from harsh solvents with the concomitant risk of harmful remnants in the final products. If we could mimic the spider's aqueous silk spinning process we would likely obtain a material that had reproducible and better characteristics and that more easily could be transferred to clinical practice. Herein, the knowledge of the spiders' silk production system and the prerequisites for artificial spinning and assembly of recombinant proteins are reviewed and discussed in a biomedical context. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Wharton's Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance

    PubMed Central

    Kalaszczynska, Ilona; Ferdyn, Katarzyna

    2015-01-01

    Around 5 million annual births in EU and 131 million worldwide give a unique opportunity to collect lifesaving Wharton's jelly derived mesenchymal stem cells (WJ-MSC). Evidences that these cells possess therapeutic properties are constantly accumulating. Collection of WJ-MSC is done at the time of delivery and it is easy and devoid of side effects associated with collection of adult stem cells from bone marrow or adipose tissue. Likewise, their rate of proliferation, immune privileged status, lack of ethical concerns, nontumorigenic properties make them ideal for both autologous and allogeneic use in regenerative medicine applications. This review provides an outline of the recent findings related to WJ-MSC therapeutic effects and possible advantage they possess over MSC from other sources. Results of first clinical trials conducted to treat immune disorders are highlighted. PMID:25861624

  7. Two- and Three-Dimensional All-Carbon Nanomaterial Assemblies for Tissue Engineering and Regenerative Medicine.

    PubMed

    Lalwani, Gaurav; Patel, Sunny C; Sitharaman, Balaji

    2016-06-01

    Carbon nanomaterials such as carbon nanotubes and graphene have gained significant interest in the fields of materials science, electronics and biomedicine due to their interesting physiochemical properties. Typically these carbon nanomaterials have been dispersed in polymeric matrices at low concentrations to improve the functional properties of nanocomposites employed as two-dimensional (2D) substrates or three-dimensional (3D) porous scaffolds for tissue engineering applications. There has been a growing interest in the assembly of these nanomaterials into 2D and 3D architectures without the use of polymeric matrices, surfactants or binders. In this article, we review recent advances in the development of 2D or 3D all-carbon assemblies using carbon nanotubes or graphene as nanoscale building-block biomaterials for tissue engineering and regenerative medicine applications.

  8. Poly(lactide-co-glycolide) porous scaffolds for tissue engineering and regenerative medicine

    PubMed Central

    Pan, Zhen; Ding, Jiandong

    2012-01-01

    Porous scaffolds fabricated from biocompatible and biodegradable polymers play vital roles in tissue engineering and regenerative medicine. Among various scaffold matrix materials, poly(lactide-co-glycolide) (PLGA) is a very popular and an important biodegradable polyester owing to its tunable degradation rates, good mechanical properties and processibility, etc. This review highlights the progress on PLGA scaffolds. In the latest decade, some facile fabrication approaches at room temperature were put forward; more appropriate pore structures were designed and achieved; the mechanical properties were investigated both for dry and wet scaffolds; a long time biodegradation of the PLGA scaffold was observed and a three-stage model was established; even the effects of pore size and porosity on in vitro biodegradation were revealed; the PLGA scaffolds have also been implanted into animals, and some tissues have been regenerated in vivo after loading cells including stem cells. PMID:23741612

  9. Osteoarthritis year in review 2014: highlighting innovations in basic research and clinical applications in regenerative medicine.

    PubMed

    van Osch, G J V M

    2014-12-01

    Regenerative medicine is an emerging area that will influence the treatment of joint diseases in the future. It involves the use of biomaterials, cell therapy, and bioactive factors such as growth factors, drugs and small molecules, to regenerate damaged tissues. This "year in review" highlights a personal selection of promising studies published between March 2013 and March 2014 that inform on the direction in which this field is moving. This multidisciplinary field has been very active, with rapid development of new technologies that emerge from basic sciences such as the possibility to generate pluripotent stem cells without genetic modification and genetic engineering of growth factors to enhance their capacity to induce tissue repair. The increasing knowledge of the interaction between all tissues in the joint, such as the effect of bone remodeling and synovial inflammation on cartilage repair, will eventually make tissue regeneration in a compromised joint environment possible.

  10. The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine

    SciTech Connect

    Anders, Juanita; Moges, Helina; Wu, Xingjia; Ilev, Ilko; Waynant, Ronald; Longo, Leonardo

    2010-05-31

    Light therapy commonly referred to as low level laser therapy can alter cellular functions and clinical conditions. Some of the commonly reported in vitro and in vivo effects of light therapy include cellular proliferation, alterations in the inflammatory response to injury, and increases in mitochondrial respiration and adenosine triphosphate synthesis. Based on the known effects of light on cells and tissues in general and on reports in the last 5 years on the interaction of light with stem cells, evidence is mounting indicating that light therapy could greatly benefit stem cell regenerative medicine. Experiments on a variety of harvested adult stem cells demonstrate that light therapy enhances differentiation and proliferation of the cells and alters the expression of growth factors in a number of different types of adult stem cells and progenitors in vitro. It also has the potential to attenuate cytotoxic effects of drugs used to purge harvested autologous stem cells and to increase survival of transplanted cells.

  11. The electrically conductive scaffold as the skeleton of stem cell niche in regenerative medicine.

    PubMed

    Jin, Guorui; Li, Kai

    2014-12-01

    Stem cells with multipotent and self-renewal abilities play a vital role in regenerative medicine and tissue engineering. They can assist tissue reconstruction through specific differentiation and secretion of various bioactive macromolecules. More and more studies confirm that the cell-fate commitment can be manipulated via constructing a specific stem cell niche. The construction of specific niches with conductive materials (conducting polymers, carbon nanotubes and graphene) can promote stem cell differentiation towards electro-active lineages and emphasize the promising role of stem cells in electro-active tissue regeneration (e.g., nerve and heart). In this review, we summarize the commonly applied conductive materials for scaffold construction and evaluate their contributions in the regeneration of electro-active tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine

    NASA Astrophysics Data System (ADS)

    Anders, Juanita; Moges, Helina; Wu, Xingjia; Ilev, Ilko; Waynant, Ronald; Longo, Leonardo

    2010-05-01

    Light therapy commonly referred to as low level laser therapy can alter cellular functions and clinical conditions. Some of the commonly reported in vitro and in vivo effects of light therapy include cellular proliferation, alterations in the inflammatory response to injury, and increases in mitochondrial respiration and adenosine triphosphate synthesis. Based on the known effects of light on cells and tissues in general and on reports in the last 5 years on the interaction of light with stem cells, evidence is mounting indicating that light therapy could greatly benefit stem cell regenerative medicine. Experiments on a variety of harvested adult stem cells demonstrate that light therapy enhances differentiation and proliferation of the cells and alters the expression of growth factors in a number of different types of adult stem cells and progenitors in vitro. It also has the potential to attenuate cytotoxic effects of drugs used to purge harvested autologous stem cells and to increase survival of transplanted cells.

  13. Regenerative Medicine in Organ and Tissue Transplantation: Shortly and Practically Achievable?

    PubMed Central

    Heidary Rouchi, A.; Mahdavi-Mazdeh, M.

    2015-01-01

    Since the beginning of organ/tissue transplantation, the therapeutic modality of choice in end-stage organ failure, organ shortage has been the main problem in transplantation medicine. Given the so far unsolved obstacle, all hope-raising procedures to possibly tackle this long-lasting problem can draw attentions. In this context, “regenerative medicine” sounds to be more promising compared to other approaches. To consider the huge impact of hematopoietic stem cell transplantation on the treatment of some congenital or acquired hematological or metabolic disorders and some advances to produce tissue engineered materials on one hand, and to take all aspects of this emerging and costly interdisciplinary field of research into consideration, on the other hand, inevitably makes this reality unchanged, in particular in countries with low or middle income, that allograft (from deceased or living donors) will remain for years as the irreplaceable source of organ transplantation. PMID:26306154

  14. Reprogramming and transdifferentiation for cardiovascular development and regenerative medicine: where do we stand?

    PubMed

    Ebert, Antje D; Diecke, Sebastian; Chen, Ian Y; Wu, Joseph C

    2015-09-01

    Heart disease remains a leading cause of mortality and a major worldwide healthcare burden. Recent advances in stem cell biology have made it feasible to derive large quantities of cardiomyocytes for disease modeling, drug development, and regenerative medicine. The discoveries of reprogramming and transdifferentiation as novel biological processes have significantly contributed to this paradigm. This review surveys the means by which reprogramming and transdifferentiation can be employed to generate induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and induced cardiomyocytes (iCMs). The application of these patient-specific cardiomyocytes for both in vitro disease modeling and in vivo therapies for various cardiovascular diseases will also be discussed. We propose that, with additional refinement, human disease-specific cardiomyocytes will allow us to significantly advance the understanding of cardiovascular disease mechanisms and accelerate the development of novel therapeutic options.

  15. Epigenetic modifications of embryonic stem cells: current trends and relevance in developing regenerative medicine.

    PubMed

    Chung, Henry; Sidhu, Kuldip S

    2008-11-17

    Epigenetics is a growing field not only in the area of cancer research but recently in stem cells including human embryonic stem cell (hESC) research. The hallmark of profiling epigenetic changes in stem cells lies in maintaining pluripotency or multipotency and in attaining lineage specifications that are relevant for regenerative medicine. Epigenetic modifications including DNA methylation, histone acetylation and methylation, play important roles in regulating gene expressions. Other epigenetic modifications include X chromosome silencing, genomic stability and imprinting and mammalian development. This review attempts to elucidate the mechanism(s) behind epigenetic modifications and review techniques scientists use for identifying each modification. We also discuss some of the trends of epigenetic modifications in the fields of directed differentiation of embryonic stem cells and de-differentiation of somatic cells.

  16. Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

    PubMed

    Charif, N; Li, Y Y; Targa, L; Zhang, L; Ye, J S; Li, Y P; Stoltz, J F; Han, H Z; de Isla, N

    2017-01-01

    With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.

  17. Collection, processing, and banking of umbilical cord blood stem cells for transplantation and regenerative medicine.

    PubMed

    Badowski, Michael S; Harris, David T

    2012-01-01

    Collection and banking of umbilical cord blood can provide a virtually unlimited source of ethnically diverse stem cell donors. It can be used in place of bone marrow or peripheral blood stem cells for hematologic transplants as well as in a variety of regenerative medicine applications. In this study, we review the latest developments in cord blood banking. We have banked over 300,000 collections at our facility, which were processed by either Ficoll or AXP methodologies. An average 95-99% processing efficiency was obtained. Processed samples can be frozen in either cryovials or bags and banked in the vapor phase of a liquid nitrogen dewar for prolonged periods of time. In conclusion, it is possible to simply and reproducibly harvest, process, and bank cord blood samples using currently available technology.

  18. The future of replacement and restorative therapies: from organ transplantation to regenerative medicine.

    PubMed

    Daar, A S

    2013-01-01

    As we continue to have severe shortages of organs for transplantation, we need to consider alternatives for the future. The most likely to make a real difference in the long term is regenerative medicine (RM), a field that has emerged from the conjunction of stem cell biology and cell therapies; gene therapy; biomaterials and tissue engineering; and organ transplantation. Transplantation and RM share the same essential goal: to replace or restore organ function. Herein I briefly review some major breakthroughs of RM that are relevant to the future of organ transplantation, with a focus on the needs of people in the developing world. A definition of RM is provided and the ethical, legal, and social issues are briefly highlighted. In conclusion, I provide a projection of what the future may be for RM.

  19. Leveraging "raw materials" as building blocks and bioactive signals in regenerative medicine.

    PubMed

    Renth, Amanda N; Detamore, Michael S

    2012-10-01

    Components found within the extracellular matrix (ECM) have emerged as an essential subset of biomaterials for tissue engineering scaffolds. Collagen, glycosaminoglycans, bioceramics, and ECM-based matrices are the main categories of "raw materials" used in a wide variety of tissue engineering strategies. The advantages of raw materials include their inherent ability to create a microenvironment that contains physical, chemical, and mechanical cues similar to native tissue, which prove unmatched by synthetic biomaterials alone. Moreover, these raw materials provide a head start in the regeneration of tissues by providing building blocks to be bioresorbed and incorporated into the tissue as opposed to being biodegraded into waste products and removed. This article reviews the strategies and applications of employing raw materials as components of tissue engineering constructs. Utilizing raw materials holds the potential to provide both a scaffold and a signal, perhaps even without the addition of exogenous growth factors or cytokines. Raw materials contain endogenous proteins that may also help to improve the translational success of tissue engineering solutions to progress from laboratory bench to clinical therapies. Traditionally, the tissue engineering triad has included cells, signals, and materials. Whether raw materials represent their own new paradigm or are categorized as a bridge between signals and materials, it is clear that they have emerged as a leading strategy in regenerative medicine. The common use of raw materials in commercial products as well as their growing presence in the research community speak to their potential. However, there has heretofore not been a coordinated or organized effort to classify these approaches, and as such we recommend that the use of raw materials be introduced into the collective consciousness of our field as a recognized classification of regenerative medicine strategies.

  20. Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine

    PubMed Central

    Renth, Amanda N.

    2012-01-01

    Components found within the extracellular matrix (ECM) have emerged as an essential subset of biomaterials for tissue engineering scaffolds. Collagen, glycosaminoglycans, bioceramics, and ECM-based matrices are the main categories of “raw materials” used in a wide variety of tissue engineering strategies. The advantages of raw materials include their inherent ability to create a microenvironment that contains physical, chemical, and mechanical cues similar to native tissue, which prove unmatched by synthetic biomaterials alone. Moreover, these raw materials provide a head start in the regeneration of tissues by providing building blocks to be bioresorbed and incorporated into the tissue as opposed to being biodegraded into waste products and removed. This article reviews the strategies and applications of employing raw materials as components of tissue engineering constructs. Utilizing raw materials holds the potential to provide both a scaffold and a signal, perhaps even without the addition of exogenous growth factors or cytokines. Raw materials contain endogenous proteins that may also help to improve the translational success of tissue engineering solutions to progress from laboratory bench to clinical therapies. Traditionally, the tissue engineering triad has included cells, signals, and materials. Whether raw materials represent their own new paradigm or are categorized as a bridge between signals and materials, it is clear that they have emerged as a leading strategy in regenerative medicine. The common use of raw materials in commercial products as well as their growing presence in the research community speak to their potential. However, there has heretofore not been a coordinated or organized effort to classify these approaches, and as such we recommend that the use of raw materials be introduced into the collective consciousness of our field as a recognized classification of regenerative medicine strategies. PMID:22462759

  1. Advanced imaging approaches for regenerative medicine: Emerging technologies for monitoring stem cell fate in vitro and in vivo.

    PubMed

    Kupfer, Molly E; Ogle, Brenda M

    2015-10-01

    The future of regenerative medicine relies on our ability to control stem cell fate in order to produce functional tissues. Stem cells are the preferred cell source for tissue engineering endeavors and regenerative medicine therapies due to their high potency and capacity for expansion. However, their potency also makes them very difficult to control, as they are in a constant state of flux. Therefore, in order to advance research in regenerative medicine, it is necessary to be able to monitor cell state and phenotype both in vitro and in vivo. This review will detail the imaging technologies currently in use to monitor stem cell phenotype, migration, and differentiation. In addition to providing examples of the most recent work in this area, we will also discuss the future of imaging technologies for regenerative medicine, and how current imaging modalities might be utilized to image specific cell functionality in order to track stem cell fate. The research area of imaging stem cells is progressing toward identifying mature and differentiating cells not only by phenotypic markers, but also by visualizing cell function. Many of the cutting-edge modalities detailed in this review have the potential to be harnessed toward this goal.

  2. Strategies for Therapeutic Repair: The “R3” Regenerative Medicine Paradigm

    PubMed Central

    Nelson, Timothy J.; Behfar, Atta; Terzic, Andre

    2008-01-01

    Abstract Beyond the palliative reach of today, medical therapies of tomorrow aim to treat the root cause of chronic degenerative diseases. Therapeutic repair encompasses the converging triad of rejuvenation, regeneration or replacement strategies that rely on self‐healing processes, stem cell regeneration, and/or organ transplantation. Natural healing or rejuvenation exemplify inherent, baseline repair secured by tissue self‐renewal and de novo cell biogenesis, particularly effective in organs with a high endogenous reparative capacity. Transplant medicine exploits the replacement strategy as a valuable option to recycle used parts and restore failing organ function by means of exogenous substitutes—it is, however, limited by donor shortage. Stem cell‐based regeneration offers the next frontier of medical therapy through delivery of essentially unlimited pools of autologous or allogeneic, naive or modified, progenitor cells to achieve structural and functional repair. Translation into clinical applications requires the establishment of a regenerative medicine community of practice capable to bridge discovery with personalized treatment solutions. Indeed, this multidisciplinary specialized workforce will be capable to integrate the new science of embryology, immunology, and stem cell biology into bioinformatics and network medicine platforms, ensuring implementation of therapeutic repair strategies into individualized disease management algorithms. PMID:19756244

  3. Physical medicine and rehabilitation: past - present - future.

    PubMed

    Fialka-Moser, V

    1999-09-01

    The inaugural lecture reflects a little on the past, but above all considers the present and future of physical medicine and rehabilitation and stresses the most important aspects on scientific expertise. Physical medicine entered the German language in the late 19th century. An important milestone in the history was the opening in February 1991 of the Central Department of Physical Medicine and Rehabilitation, which was the first to begin work in the New General Hospital. 15 staff doctors, 74 physiotherapists, 12 occupational therapists, seven masseurs and eight qualified medical assistants are constantly occupied in clinical practise. To illustrate the recent academic activities at the Department of Physical Medicine and Rehabilitation the results of research from the individual working groups are compiled. First clinical and technical diagnostic studies are focused on. Essentially such studies demonstrate the efficacy of physical treatments, which are being reported. Current rehabilitation concepts are presented subsequently. Finally some light is shed on future areas of interest.

  4. The pluralization of the international: Resistance and alter-standardization in regenerative stem cell medicine

    PubMed Central

    Rosemann, Achim; Chaisinthop, Nattaka

    2016-01-01

    The article explores the formation of an international politics of resistance and ‘alter-standardization’ in regenerative stem cell medicine. The absence of internationally harmonized regulatory frameworks in the clinical stem cell field and the presence of lucrative business opportunities have resulted in the formation of transnational networks adopting alternative research standards and practices. These oppose, as a universal global standard, strict evidence-based medicine clinical research protocols as defined by scientists and regulatory agencies in highly developed countries. The emergence of transnational spaces of alter-standardization is closely linked to scientific advances in rapidly developing countries such as China and India, but calls for more flexible regulatory frameworks, and the legitimization of experimental for-profit applications outside of evidence-based medical care, are emerging increasingly also within more stringently regulated countries, such as the United States and countries in the European Union. We can observe, then, a trend toward the pluralization of the standards, practices, and concepts in the stem cell field. PMID:26983174

  5. Preservation of Ocular Epithelial Limbal Stem Cells: The New Frontier in Regenerative Medicine.

    PubMed

    Lužnik, Zala; Bertolin, Marina; Breda, Claudia; Ferrari, Barbara; Barbaro, Vanessa; Schollmayer, Petra; Ferrari, Stefano

    2016-01-01

    Significant advances have been made in the field of ocular regenerative medicine. Promising stem cell-based therapeutic strategies have been translated into the clinical practice over the last few decades. These new stem cell-based therapies offer the possibility of permanently restoring corneal epithelium in patients with severe disabling and blinding ocular surface disease. The European Union has already classified stem cell-based therapies as "medicinal products". Therefore, manipulation is strictly regulated according to the defined conditions of good manufacturing practice, with the production of stem cell therapeutics at only accredited production sites authorized by the national regulatory agencies. In this regard, as first medical products are licensed for commercial use in Europe enabling a more widespread access to a stem cell-based therapy, the need for safe, validated and reproducible techniques for ex vivo cultured tissue preservation and distribution are coming to the forefront of research. However, these provide various new challenges for biobanking industry such as the retention of viability, good functionality of stem cells and sterility issues. This chapter provides an overview of the current advances in the field of corneal/limbal epithelial stem cell culture preservation techniques using either hypothermic storage or cryopreservation methods, that were used in different culturing steps (from stem cell isolation to the ex vivo epithelial graft preparation), with the reported impact on the post-thawing product recovery.

  6. Regenerative medicine: then and now--an update of recent history into future possibilities.

    PubMed

    Polykandriotis, E; Popescu, L M; Horch, R E

    2010-10-01

    The fields of tissue engineering (TE) and regenerative medicine (RegMed) are yet to bring about the anticipated therapeutic revolution. After two decades of extremely high expectations and often disappointing returns both in the medical as well as in the financial arena, this scientific field reflects the sense of a new era and suggests the feeling of making a fresh start although many scientists are probably seeking reorientation. Much of research was industry driven, so that especially in the aftermath of the recent financial meltdown in the last 2 years we have witnessed a biotech asset yard sale. Despite any monetary shortcomings, from a technological point of view there have been great leaps that are yet to find their way to the patient. RegMed is definitely bound to play a major role in our life because it embodies one of the primordial dreams of mankind, such as: everlasting youth, flying, remote communication and setting foot on the moon. The Journal of Cellular and Molecular Medicine has been at the frontier of these developments in TE and RegMed from its beginning and reflects recent scientific advances in both fields. Therefore this review tries to look at RegMed through the keyhole of history which might just be like looking 'back to the future'.

  7. Law's performativities: shaping the emergence of regenerative medicine through European Union legislation.

    PubMed

    Faulkner, Alex

    2012-10-01

    The paper undertakes a textual and documentary analysis of the Advanced Therapy Medicinal Products Regulation, which was passed into law in the European Union (EU) in 2007. This law is significant for the development of regenerative medicine in the EU and globally. Regulatory texts such as this one provide significant material for addressing key concerns in recent theorising about innovative technologies in socio-legal studies, innovation studies, and science and technology studies. These concerns include expectations about future technologies and economic sector-building. By revisiting philosopher J.L. Austin's well-known work on How to Do Things with Words, this paper deploys his concepts of performative utterances to inform its analysis. Pursuing Austin's and later commentators' analysis of performatives in language use, and drawing on Lindsay Prior's application of actor-network theory to documents, the analysis shows two different types of performativity at work in and through the document. These are termed 'generative' and 'enactive' performativity. The 'enactive' type includes 'legislative' and 'social' forms. In addition, a more conventional content analysis reveals a range of actions, both legislative and discursive, in the regulatory document. The analysis shows a tension between standardisation and imprecision in the conceptual detailing of the document. Legislative texts produced through established politico-legal conventions are a special class of document that should be accorded a more prominent place in understanding the role of political governance processes in shaping emergent technoscientific fields and sectors.

  8. Regenerative medicine: then and now – an update of recent history into future possibilities

    PubMed Central

    Polykandriotis, E; Popescu, L M; Horch, R E

    2010-01-01

    Abstract The fields of tissue engineering (TE) and regenerative medicine (RegMed) are yet to bring about the anticipated therapeutic revolution. After two decades of extremely high expectations and often disappointing returns both in the medical as well as in the financial arena, this scientific field reflects the sense of a new era and suggests the feeling of making a fresh start although many scientists are probably seeking reorientation. Much of research was industry driven, so that especially in the aftermath of the recent financial meltdown in the last 2 years we have witnessed a biotech asset yard sale. Despite any monetary shortcomings, from a technological point of view there have been great leaps that are yet to find their way to the patient. RegMed is definitely bound to play a major role in our life because it embodies one of the primordial dreams of mankind, such as: everlasting youth, flying, remote communication and setting foot on the moon. The Journal of Cellular and Molecular Medicine has been at the frontier of these developments in TE and RegMed from its beginning and reflects recent scientific advances in both fields. Therefore this review tries to look at RegMed through the keyhole of history which might just be like looking ‘back to the future’. PMID:20825521

  9. The pluralization of the international: Resistance and alter-standardization in regenerative stem cell medicine.

    PubMed

    Rosemann, Achim; Chaisinthop, Nattaka

    2016-02-01

    The article explores the formation of an international politics of resistance and 'alterstandardization' in regenerative stem cell medicine. The absence of internationally harmonized regulatory frameworks in the clinical stem cell field and the presence of lucrative business opportunities have resulted in the formation of transnational networks adopting alternative research standards and practices. These oppose, as a universal global standard, strict evidence-based medicine clinical research protocols as defined by scientists and regulatory agencies in highly developed countries. The emergence of transnational spaces of alter-standardization is closely linked to scientific advances in rapidly developing countries such as China and India, but calls for more flexible regulatory frameworks, and the legitimization of experimental for-profit applications outside of evidence-based medical care, are emerging increasingly also within more stringently regulated countries, such as the United States and countries in the European Union. We can observe, then, a trend toward the pluralization of the standards, practices, and concepts in the stem cell field.

  10. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.

    PubMed

    Richardson, Stephen M; Kalamegam, Gauthaman; Pushparaj, Peter N; Matta, Csaba; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Reza; Poletti, Fabian L; Hoyland, Judith A; Mobasheri, Ali

    2016-04-15

    Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

  11. The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal.

    PubMed Central

    Hettle, Robert; Corbett, Mark; Hinde, Sebastian; Hodgson, Robert; Jones-Diette, Julie; Woolacott, Nerys; Palmer, Stephen

    2017-01-01

    BACKGROUND The National Institute for Health and Care Excellence (NICE) commissioned a 'mock technology appraisal' to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal. METHODS Our research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia. RESULTS An assessment of previous evaluations of regenerative medicines found that, although there were a number of evidential challenges, none was unique to regenerative medicines or was beyond the scope of existing methods used to conceptualise decision uncertainty. Regarding the clinical evidence for regenerative medicines, the issues were those associated with a limited evidence base but were not unique to regenerative medicines: small non-randomised studies, high variation in response and the intervention subject to continuing development. The relative treatment effects generated from single-arm trials are likely to be optimistic unless it is certain that the historical data have accurately estimated the efficacy of the control agent. Pivotal trials may use surrogate end points, which, on average, overestimate treatment effects. To reduce overall uncertainty, multivariate meta-analysis of all available data should be considered. Incorporating indirectly relevant but more reliable (more mature) data into the analysis can also be considered; such data may become available as a result of the evolving regulatory pathways being developed by the European Medicines Agency. For the exemplar case of CAR T-cell therapy, target product profiles (TPPs) were developed, which considered the 'curative' and 'bridging to stem

  12. GMP Cryopreservation of Large Volumes of Cells for Regenerative Medicine: Active Control of the Freezing Process

    PubMed Central

    Massie, Isobel; Selden, Clare; Hodgson, Humphrey; Gibbons, Stephanie; Morris, G. John

    2014-01-01

    Cryopreservation protocols are increasingly required in regenerative medicine applications but must deliver functional products at clinical scale and comply with Good Manufacturing Process (GMP). While GMP cryopreservation is achievable on a small scale using a Stirling cryocooler-based controlled rate freezer (CRF) (EF600), successful large-scale GMP cryopreservation is more challenging due to heat transfer issues and control of ice nucleation, both complex events that impact success. We have developed a large-scale cryocooler-based CRF (VIA Freeze) that can process larger volumes and have evaluated it using alginate-encapsulated liver cell (HepG2) spheroids (ELS). It is anticipated that ELS will comprise the cellular component of a bioartificial liver and will be required in volumes of ∼2 L for clinical use. Sample temperatures and Stirling cryocooler power consumption was recorded throughout cooling runs for both small (500 μL) and large (200 mL) volume samples. ELS recoveries were assessed using viability (FDA/PI staining with image analysis), cell number (nuclei count), and function (protein secretion), along with cryoscanning electron microscopy and freeze substitution techniques to identify possible injury mechanisms. Slow cooling profiles were successfully applied to samples in both the EF600 and the VIA Freeze, and a number of cooling and warming profiles were evaluated. An optimized cooling protocol with a nonlinear cooling profile from ice nucleation to −60°C was implemented in both the EF600 and VIA Freeze. In the VIA Freeze the nucleation of ice is detected by the control software, allowing both noninvasive detection of the nucleation event for quality control purposes and the potential to modify the cooling profile following ice nucleation in an active manner. When processing 200 mL of ELS in the VIA Freeze—viabilities at 93.4%±7.4%, viable cell numbers at 14.3±1.7 million nuclei/mL alginate, and protein secretion at 10.5±1.7

  13. GMP cryopreservation of large volumes of cells for regenerative medicine: active control of the freezing process.

    PubMed

    Massie, Isobel; Selden, Clare; Hodgson, Humphrey; Fuller, Barry; Gibbons, Stephanie; Morris, G John

    2014-09-01

    Cryopreservation protocols are increasingly required in regenerative medicine applications but must deliver functional products at clinical scale and comply with Good Manufacturing Process (GMP). While GMP cryopreservation is achievable on a small scale using a Stirling cryocooler-based controlled rate freezer (CRF) (EF600), successful large-scale GMP cryopreservation is more challenging due to heat transfer issues and control of ice nucleation, both complex events that impact success. We have developed a large-scale cryocooler-based CRF (VIA Freeze) that can process larger volumes and have evaluated it using alginate-encapsulated liver cell (HepG2) spheroids (ELS). It is anticipated that ELS will comprise the cellular component of a bioartificial liver and will be required in volumes of ∼2 L for clinical use. Sample temperatures and Stirling cryocooler power consumption was recorded throughout cooling runs for both small (500 μL) and large (200 mL) volume samples. ELS recoveries were assessed using viability (FDA/PI staining with image analysis), cell number (nuclei count), and function (protein secretion), along with cryoscanning electron microscopy and freeze substitution techniques to identify possible injury mechanisms. Slow cooling profiles were successfully applied to samples in both the EF600 and the VIA Freeze, and a number of cooling and warming profiles were evaluated. An optimized cooling protocol with a nonlinear cooling profile from ice nucleation to -60°C was implemented in both the EF600 and VIA Freeze. In the VIA Freeze the nucleation of ice is detected by the control software, allowing both noninvasive detection of the nucleation event for quality control purposes and the potential to modify the cooling profile following ice nucleation in an active manner. When processing 200 mL of ELS in the VIA Freeze-viabilities at 93.4% ± 7.4%, viable cell numbers at 14.3 ± 1.7 million nuclei/mL alginate, and protein secretion at 10.5 ± 1.7

  14. The regenerative medicine in oral and maxillofacial surgery: the most important innovations in the clinical application of mesenchymal stem cells.

    PubMed

    Tatullo, Marco; Marrelli, Massimo; Paduano, Francesco

    2015-01-01

    Regenerative medicine is an emerging field of biotechnology that combines various aspects of medicine, cell and molecular biology, materials science and bioengineering in order to regenerate, repair or replace tissues. The oral surgery and maxillofacial surgery have a role in the treatment of traumatic or degenerative diseases that lead to a tissue loss: frequently, to rehabilitate these minuses, you should use techniques that have been improved over time. Since 1990, we started with the use of growth factors and platelet concentrates in oral and maxillofacial surgery; in the following period we start to use biomaterials, as well as several type of scaffolds and autologous tissues. The frontier of regenerative medicine nowadays is represented by the mesenchymal stem cells (MSCs): overcoming the ethical problems thanks to the use of mesenchymal stem cells from adult patient, and with the increasingly sophisticated technology to support their manipulation, MSCs are undoubtedly the future of medicine regenerative and they are showing perspectives unimaginable just a few years ago. Most recent studies are aimed to tissues regeneration using MSCs taken from sites that are even more accessible and rich in stem cells: the oral cavity turned out to be an important source of MSCs with the advantage to be easily accessible to the surgeon, thus avoiding to increase the morbidity of the patient. The future is the regeneration of whole organs or biological systems consisting of many different tissues, starting from an initial stem cell line, perhaps using innovative scaffolds together with the nano-engineering of biological tissues.

  15. [Regenerative approach for COPD].

    PubMed

    Kubo, Hiroshi

    2011-10-01

    No treatment to cure of chronic obstructive pulmonary disease (COPD) is available. Regenerative medicine is one of promising areas for this intractable disease. Several reagents and growth factors are known to promote lung regeneration in small animal models. However, regenerative medicines for human lungs are not achieved yet. Recent advances in stem cell biology and tissue engineering have expanded our understanding of lung endogenous stem cells, and this new knowledge provides us with new ideas for future regenerative therapy for lung diseases. Although lungs are the most challenging organ for regenerative medicine, our cumulative knowledge of lung regeneration and of endogenous progenitor cells makes clear the possibilities for regenerative approach to COPD.

  16. Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine.

    PubMed

    Kingham, Emmajayne; Oreffo, Richard O C

    2013-03-26

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any specialized cell type of the human body, and therefore, ESC/iPSC-derived cell types offer great potential for regenerative medicine. However, key to realizing this potential requires a strong understanding of stem cell biology, techniques to maintain stem cells, and strategies to manipulate cells to efficiently direct cell differentiation toward a desired cell type. As nanoscale science and engineering continues to produce novel nanotechnology platforms, which inform, infiltrate, and impinge on many aspects of everyday life, it is no surprise that stem cell research is turning toward developments in nanotechnology to answer research questions and to overcome obstacles in regenerative medicine. Here we discuss recent advances in ESC and iPSC manipulation using nanomaterials and highlight future challenges within this area of research.

  17. Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance.

    PubMed

    Hutmacher, Dietmar Werner; Holzapfel, Boris Michael; De-Juan-Pardo, Elena Maria; Pereira, Brooke Anne; Ellem, Stuart John; Loessner, Daniela; Risbridger, Gail Petuna

    2015-12-01

    In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

  18. Embryonic and Induced Pluripotent Stem Cells: Understanding, Creating, and Exploiting the Nano-Niche for Regenerative Medicine

    PubMed Central

    2013-01-01

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any specialized cell type of the human body, and therefore, ESC/iPSC-derived cell types offer great potential for regenerative medicine. However, key to realizing this potential requires a strong understanding of stem cell biology, techniques to maintain stem cells, and strategies to manipulate cells to efficiently direct cell differentiation toward a desired cell type. As nanoscale science and engineering continues to produce novel nanotechnology platforms, which inform, infiltrate, and impinge on many aspects of everyday life, it is no surprise that stem cell research is turning toward developments in nanotechnology to answer research questions and to overcome obstacles in regenerative medicine. Here we discuss recent advances in ESC and iPSC manipulation using nanomaterials and highlight future challenges within this area of research. PMID:23414366

  19. Future role of MR elastography in tissue engineering and regenerative medicine.

    PubMed

    Othman, Shadi F; Xu, Huihui; Mao, Jeremy J

    2015-05-01

    Tissue engineering (TE) has been introduced for more than 25 years without a boom in clinical trials. More than 70 TE-related start-up companies spent more than $600 million/year, with only two FDA-approved tissue-engineered products. Given the modest performance in clinically approved organs, TE is a tenaciously promising field. The TE community is advocating the application of clinically driven methodologies in large animal models enabling clinical translation. This challenge is hindered by the scarcity of tissue biopsies and the absence of standardized evaluation tools, but can be negated through non-invasive assessment of growth and integration, with reduced sample size and low cost. Solving this issue will speed the transition to cost-efficient clinical studies. In this paper we: (a) introduce magnetic resonance elastography to the tissue-engineering and regenerative medicine (TERM) community; (b) review recent MRE applications in TERM; and (c) discuss future directions of MRE in TERM. We have used MRE to study engineered tissues both in vitro and in vivo, where the mechanical properties of mesenchymally derived constructs were progressively monitored before and after tissues were implanted in mouse models. This study represents a stepping stone toward the applications of MRE in directing clinical trials with low cost and likely expediting the translation to more relevantly large animal models and clinical trials.

  20. Performance of PRP Associated with Porous Chitosan as a Composite Scaffold for Regenerative Medicine

    PubMed Central

    Shimojo, Andréa Arruda Martins; Perez, Amanda Gomes Marcelino; Galdames, Sofia Elisa Moraga; Brissac, Isabela Cambraia de Souza; Santana, Maria Helena Andrade

    2015-01-01

    This study aimed to evaluate the in vitro performance of activated platelet-rich plasma associated with porous sponges of chitosan as a composite scaffold for proliferation and osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. The sponges were prepared by controlled freezing (−20, −80, or −196°C) and lyophilization of chitosan solutions (1, 2, or 3% w/v). The platelet-rich plasma was obtained from controlled centrifugation of whole blood and activated with calcium and autologous serum. The composite scaffolds were prepared by embedding the sponges with the activated platelet-rich plasma. The results showed the performance of the scaffolds was superior to that of activated platelet-rich plasma alone, in terms of delaying the release of growth factors and increased proliferation of the stem cells. The best preparation conditions of chitosan composite scaffolds that coordinated the physicochemical and mechanical properties and cell proliferation were 3% (w/v) chitosan and a −20°C freezing temperature, while −196°C favored osteogenic differentiation. Although the composite scaffolds are promising for regenerative medicine, the structures require stabilization to prevent the collapse observed after five days. PMID:25821851

  1. Latest status of the clinical and industrial applications of cell sheet engineering and regenerative medicine.

    PubMed

    Egami, Mime; Haraguchi, Yuji; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

    2014-01-01

    Cell sheet engineering, which allows tissue engineering to be realized without the use of biodegradable scaffolds as an original approach, using a temperature-responsive intelligent surface, has been applied in regenerative medicine for various tissues, and a number of clinical studies have been already performed for life-threatening diseases. By using the results and findings obtained from the initial clinical studies, additional investigative clinical studies in several tissues with cell sheet engineering are currently in preparation stage. For treating many patients effectively by cell sheet engineering, an automated system integrating cell culture, cell-sheet fabrication, and layering is essential, and the system should include an advanced three-dimensional suspension cell culture system and an in vitro bioreactor system to scale up the production of cultured cells and fabricate thicker vascularized tissues. In this paper, cell sheet engineering, its clinical application, and further the authors' challenge to develop innovative cell culture systems under newly legislated regulatory platform in Japan are summarized and discussed.

  2. 25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

    PubMed Central

    Annabi, Nasim; Tamayol, Ali; Uquillas, Jorge Alfredo; Akbari, Mohsen; Bertassoni, Luiz E.; Cha, Chaenyung; Camci-Unal, Gulden; Dokmeci, Mehmet R.

    2014-01-01

    Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life. PMID:24741694

  3. Development of the hyperspectral cellular imaging system to apply to regenerative medicine

    NASA Astrophysics Data System (ADS)

    Ishihara, Miya; Sato, Masato; Matsumura, Kouji; Mochida, Joji; Kikuchi, Makoto

    2010-02-01

    Regenerative medicine by the transplantation of differentiated cells or tissue stem cells has been clinically performed, particularly in the form of cell sheets. To ensure the safety and effectiveness of cell therapy, the efficient selection of desired cells with high quality is a critical issue, which requires the development of a new evaluation method to discriminate cells non-invasively with high throughput. There were many ways to characterize cells and their components, among which the optical spectral analysis has a powerful potential for this purpose. We developed a cellular hyperspectral imaging system, which captured both spatial and spectral information in a single pixel. Hyperspectral data are composed of continual spectral bands, whereas multispectral data are usually composed of about 5 to 10 discrete bands of large bandwidths. The hyperspectral imaging system which we developed was set up by a commonly-used inverted light microscope for cell culture experiments, and the time-lapse imaging system with automatic focus correction. Spectral line imaging device with EMCCD was employed for spectral imaging. The system finally enabled to acquire 5 dimensional (x, y, z, time, wavelength) data sets and cell-by-cell evaluation. In this study, we optimized the protocol for the creation of cellular spectral database under biological understanding. We enabled to confirm spectrum of autofluorescence of collagen, absorption of specific molecules in the cultural sample and increase of scattering signal due to cell components although detail spectral analyses have not been performed.

  4. Adipose tissue-derived stem cells show considerable promise for regenerative medicine applications.

    PubMed

    Harasymiak-Krzyżanowska, Izabela; Niedojadło, Alicja; Karwat, Jolanta; Kotuła, Lidia; Gil-Kulik, Paulina; Sawiuk, Magdalena; Kocki, Janusz

    2013-12-01

    The stromal-vascular cell fraction (SVF) of adipose tissue can be an abundant source of both multipotent and pluripotent stem cells, known as adipose-derived stem cells or adipose tissue-derived stromal cells (ADSCs). The SVF also contains vascular cells, targeted progenitor cells, and preadipocytes. Stromal cells isolated from adipose tissue express common surface antigens, show the ability to adhere to plastic, and produce forms that resemble fibroblasts. They are characterized by a high proliferation potential and the ability to differentiate into cells of meso-, ecto- and endodermal origin. Although stem cells obtained from an adult organism have smaller capabilities for differentiation in comparison to embryonic and induced pluripotent stem cells (iPSs), the cost of obtaining them is significantly lower. The 40 years of research that mainly focused on the potential of bone marrow stem cells (BMSCs) revealed a number of negative factors: the painful sampling procedure, frequent complications, and small cell yield. The number of stem cells in adipose tissue is relatively large, and obtaining them is less invasive. Sampling through simple procedures such as liposuction performed under local anesthesia is less painful, ensuring patient comfort. The isolated cells are easily grown in culture, and they retain their properties over many passages. That is why adipose tissue has recently been treated as an attractive alternative source of stem cells. Essential aspects of ADSC biology and their use in regenerative medicine will be analyzed in this article.

  5. Concise review: reprogramming strategies for cardiovascular regenerative medicine: from induced pluripotent stem cells to direct reprogramming.

    PubMed

    Budniatzky, Inbar; Gepstein, Lior

    2014-04-01

    Myocardial cell-replacement therapies are emerging as novel therapeutic paradigms for myocardial repair but are hampered by the lack of sources of autologous human cardiomyocytes. The recent advances in stem cell biology and in transcription factor-based reprogramming strategies may provide exciting solutions to this problem. In the current review, we describe the different reprogramming strategies that can give rise to cardiomyocytes for regenerative medicine purposes. Initially, we describe induced pluripotent stem cell technology, a method by which adult somatic cells can be reprogrammed to yield pluripotent stem cells that could later be coaxed ex vivo to differentiate into cardiomyocytes. The generated induced pluripotent stem cell-derived cardiomyocytes could then be used for myocardial cell transplantation and tissue engineering strategies. We also describe the more recent direct reprogramming approaches that aim to directly convert the phenotype of one mature cell type (fibroblast) to another (cardiomyocyte) without going through a pluripotent intermediate cell type. The advantages and shortcomings of each strategy for cardiac regeneration are discussed, along with the hurdles that need to be overcome on the road to clinical translation.

  6. Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications.

    PubMed

    Mull, Amber N; Zolekar, Ashwini; Wang, Yu-Chieh

    2015-12-21

    Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte stem cells (McSCs) residing in the epidermis of the skin. Many preceding studies have led to significant discoveries regarding the cellular and molecular characteristics of this unique stem cell population. The alteration of McSCs has been also implicated in several skin abnormalities and disease conditions. To date, our knowledge of McSCs largely comes from studying the stem cell niche of mouse hair follicles. Suggested by several anatomical differences between mouse and human skin, there could be distinct features associated with mouse and human McSCs as well as their niches in the skin. Recent advances in human pluripotent stem cell (hPSC) research have provided us with useful tools to potentially acquire a substantial amount of human McSCs and functional melanocytes for research and regenerative medicine applications. This review highlights recent studies and progress involved in understanding the development of cutaneous melanocytes and the regulation of McSCs.

  7. Mesenchymal stem cells and their subpopulation, pluripotent muse cells, in basic research and regenerative medicine.

    PubMed

    Kuroda, Yasumasa; Dezawa, Mari

    2014-01-01

    Mesenchymal stem cells (MSCs) have gained a great deal of attention for regenerative medicine because they can be obtained from easy accessible mesenchymal tissues, such as bone marrow, adipose tissue, and the umbilical cord, and have trophic and immunosuppressive effects to protect tissues. The most outstanding property of MSCs is their potential for differentiation into cells of all three germ layers. MSCs belong to the mesodermal lineage, but they are known to cross boundaries from mesodermal to ectodermal and endodermal lineages, and differentiate into a variety of cell types both in vitro and in vivo. Such behavior is exceptional for tissue stem cells. As observed with hematopoietic and neural stem cells, tissue stem cells usually generate cells that belong to the tissue in which they reside, and do not show triploblastic differentiation. However, the scientific basis for the broad multipotent differentiation of MSCs still remains an enigma. This review summarizes the properties of MSCs from representative mesenchymal tissues, including bone marrow, adipose tissue, and the umbilical cord, to demonstrate their similarities and differences. Finally, we introduce a novel type of pluripotent stem cell, multilineage-differentiating stress-enduring (Muse) cells, a small subpopulation of MSCs, which can explain the broad spectrum of differentiation ability in MSCs.

  8. Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications

    PubMed Central

    Mull, Amber N.; Zolekar, Ashwini; Wang, Yu-Chieh

    2015-01-01

    Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte stem cells (McSCs) residing in the epidermis of the skin. Many preceding studies have led to significant discoveries regarding the cellular and molecular characteristics of this unique stem cell population. The alteration of McSCs has been also implicated in several skin abnormalities and disease conditions. To date, our knowledge of McSCs largely comes from studying the stem cell niche of mouse hair follicles. Suggested by several anatomical differences between mouse and human skin, there could be distinct features associated with mouse and human McSCs as well as their niches in the skin. Recent advances in human pluripotent stem cell (hPSC) research have provided us with useful tools to potentially acquire a substantial amount of human McSCs and functional melanocytes for research and regenerative medicine applications. This review highlights recent studies and progress involved in understanding the development of cutaneous melanocytes and the regulation of McSCs. PMID:26703580

  9. Emerging roles of hyaluronic acid bioscaffolds in tissue engineering and regenerative medicine.

    PubMed

    Hemshekhar, Mahadevappa; Thushara, Ram M; Chandranayaka, Siddaiah; Sherman, Larry S; Kemparaju, Kempaiah; Girish, Kesturu S

    2016-05-01

    Hyaluronic acid (HA), is a glycosaminoglycan comprised of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid. HA is synthesized by hyaluronan synthases and reaches sizes in excess of 2MDa. It plays numerous roles in normal tissues but also has been implicated in inflammatory processes, multiple drug resistance, angiogenesis, tumorigenesis, water homeostasis, and altered viscoelasticity of extracellular matrix. The physicochemical properties of HA including its solubility and the availability of reactive functional groups facilitate chemical modifications on HA, which makes it a biocompatible material for use in tissue regeneration. HA-based biomaterials and bioscaffolds do not trigger allergies or inflammation and are hydrophilic which make them popular as injectable dermal and soft tissue fillers. They are manufactured in different forms including hydrogels, tubes, sheets and meshes. Here, we review the pathophysiological and pharmacological properties and the clinical uses of native and modified HA. The review highlights the therapeutic applications of HA-based bioscaffolds in organ-specific tissue engineering and regenerative medicine.

  10. Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

    PubMed Central

    Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul

    2014-01-01

    In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future. PMID:25143954

  11. A Retrospective Look at Integrating a Novel Regenerative Medicine Approach in Plastic Limb Reconstruction

    PubMed Central

    Rathbone, Christopher R.; Barnes, Brian R.

    2017-01-01

    Full-thickness wounds that have rendered patients candidates for amputation may require techniques that may include a combinatorial approach above traditional standard of care. The purpose of this retrospective study was to evaluate the effectiveness of an innovative approach whereby several therapies were combined to avoid amputation. Patients with full-thickness wounds who were previously recommended for amputation and were treated with the combinatorial approach of muscle flap reconstruction and concentrated bone marrow aspirate, platelet-rich plasma, INTEGRA Wound matrix, vacuum-assisted closure, and split-thickness skin grafts were assessed retrospectively. The mean age of the patients identified was 48 years (range, 34–66 years). The average size of the defects was 19.6 cm2. All defects were successfully covered with medial hemisoleus, lateral hemisoleus, or peroneus brevis muscle flaps combined with split-thickness skin grafts, concentrated bone marrow aspirate, and platelet-rich plasma. All flaps healed with an average time to fixator removal of 8.3 weeks; there was 1 above-knee amputation that occurred approximately after successful wound closing and fixator removal. The combinatorial approach described here including several regenerative medicine tools is an effective means of lower limb reconstruction to avoid amputation. PMID:28203511

  12. Application of elastin-mimetic recombinant proteins in chemotherapeutics delivery, cellular engineering, and regenerative medicine.

    PubMed

    Jeon, Won Bae

    2013-01-01

    With the remarkable increase in the fields of biomedical engineering and regenerative medicine, biomaterial design has become an indispensable approach for developing the biocompatible carriers for drug or gene cargo and extracellular matrix (ECM) for cell survival, proliferation and differentiation. Native ECM materials derived from animal tissues were believed to be the best choices for tissue engineering. However, possible pathogen contamination by cellular remnants from foreign animal tissues is an unavoidable issue that has limited the use of native ECM for human benefit. Some synthetic polymers have been used as alternative materials for manufacturing native ECM because of the biodegradability and ease of large-scale production of the polymers. However, the inherent polydispersity of the polymers causes batch-to-batch variation in polymer composition and possible cytotoxic interactions between chemical matrices and neighboring cells or tissues have not yet been fully resolved. Elastin-like proteins (ELPs) are genetically engineered biopolymers modeled after the naturally occurring tropoelastin and have emerged as promising materials for biomedical applications because they are biocompatible, non-immunogenic and biodegradable, and their composition, mechanical stiffness and even fate within the cell can be controlled at the gene level. This commentary highlights the recent progresses in the development of the ELP-based recombinant proteins that are being increasingly used for the delivery of chemotherapeutics and to provide a cell-friendly ECM environment.

  13. Application of elastin-mimetic recombinant proteins in chemotherapeutics delivery, cellular engineering, and regenerative medicine

    PubMed Central

    Jeon, Won Bae

    2013-01-01

    With the remarkable increase in the fields of biomedical engineering and regenerative medicine, biomaterial design has become an indispensable approach for developing the biocompatible carriers for drug or gene cargo and extracellular matrix (ECM) for cell survival, proliferation and differentiation. Native ECM materials derived from animal tissues were believed to be the best choices for tissue engineering. However, possible pathogen contamination by cellular remnants from foreign animal tissues is an unavoidable issue that has limited the use of native ECM for human benefit. Some synthetic polymers have been used as alternative materials for manufacturing native ECM because of the biodegradability and ease of large-scale production of the polymers. However, the inherent polydispersity of the polymers causes batch-to-batch variation in polymer composition and possible cytotoxic interactions between chemical matrices and neighboring cells or tissues have not yet been fully resolved. Elastin-like proteins (ELPs) are genetically engineered biopolymers modeled after the naturally occurring tropoelastin and have emerged as promising materials for biomedical applications because they are biocompatible, non-immunogenic and biodegradable, and their composition, mechanical stiffness and even fate within the cell can be controlled at the gene level. This commentary highlights the recent progresses in the development of the ELP-based recombinant proteins that are being increasingly used for the delivery of chemotherapeutics and to provide a cell-friendly ECM environment. PMID:23475122

  14. The social management of biomedical novelty: Facilitating translation in regenerative medicine.

    PubMed

    Gardner, John; Webster, Andrew

    2016-05-01

    Regenerative medicine (RM) is championed as a potential source of curative treatments for a variety of illnesses, and as a generator of economic wealth and prosperity. Alongside this optimism, however, is a sense of concern that the translation of basic science into useful RM therapies will be laboriously slow due to a range of challenges relating to live tissue handling and manufacturing, regulation, reimbursement and commissioning, and clinical adoption. This paper explores the attempts of stakeholders to overcome these innovation challenges and thus facilitate the emergence of useful RM therapies. The paper uses the notion of innovation niches as an analytical frame. Innovation niches are collectively constructed socio-technical spaces in which a novel technology can be tested and further developed, with the intention of enabling wider adoption. Drawing on primary and secondary data, we explore the motivation for, and the attempted construction of, niches in three domains which are central to the adoption of innovative technologies: the regulatory, the health economic, and the clinical. We illustrate that these niches are collectively constructed via both formal and informal initiatives, and we argue that they reflect wider socio-political trends in the social management of biomedical novelty.

  15. Embryonic stem cells and prospects for their use in regenerative medicine approaches to motor neurone disease.

    PubMed

    Christou, Y A; Moore, H D; Shaw, P J; Monk, P N

    2007-10-01

    Human embryonic stem cells are pluripotent cells with the potential to differentiate into any cell type in the presence of appropriate stimulatory factors and environmental cues. Their broad developmental potential has led to valuable insights into the principles of developmental and cell biology and to the proposed use of human embryonic stem cells or their differentiated progeny in regenerative medicine. This review focuses on the prospects for the use of embryonic stem cells in cell-based therapy for motor neurone disease or amyotrophic lateral sclerosis, a progressive neurodegenerative disease that specifically affects upper and lower motor neurones and leads ultimately to death from respiratory failure. Stem cell-derived motor neurones could conceivably be used to replace the degenerated cells, to provide authentic substrates for drug development and screening and for furthering our understanding of disease mechanisms. However, to reliably and accurately culture motor neurones, the complex pathways by which differentiation occurs in vivo must be understood and reiterated in vitro by embryonic stem cells. Here we discuss the need for new therapeutic strategies in the treatment of motor neurone disease, the developmental processes that result in motor neurone formation in vivo, a number of experimental approaches to motor neurone production in vitro and recent progress in the application of stem cells to the treatment and understanding of motor neurone disease.

  16. Regenerative medicine for the respiratory system: distant future or tomorrow's treatment?

    PubMed

    Brouwer, Katrien M; Hoogenkamp, Henk R; Daamen, Willeke F; van Kuppevelt, Toin H

    2013-03-01

    Regenerative medicine (RM) is a new field of biomedical science that focuses on the regeneration of tissues and organs and the restoration of organ function. Although regeneration of organ systems such as bone, cartilage, and heart has attracted intense scientific research over recent decades, RM research regarding the respiratory system, including the trachea, the lung proper, and the diaphragm, has lagged behind. However, the last 5 years have witnessed novel approaches and initial clinical applications of tissue-engineered constructs to restore organ structure and function. In this regard, this article briefly addresses the basics of RM and introduces the key elements necessary for tissue regeneration, including (stem) cells, biomaterials, and extracellular matrices. In addition, the current status of the (clinical) application of RM to the respiratory system is discussed, and bottlenecks and recent approaches are identified. For the trachea, several initial clinical studies have been reported and have used various combinations of cells and scaffolds. Although promising, the methods used in these studies require optimization and standardization. For the lung proper, only (stem) cell-based approaches have been probed clinically, but it is becoming apparent that combinations of cells and scaffolds are required to successfully restore the lung's architecture and function. In the case of the diaphragm, clinical applications have focused on the use of decellularized scaffolds, but novel scaffolds, with or without cells, are clearly needed for true regeneration of diaphragmatic tissue. We conclude that respiratory treatment with RM will not be realized tomorrow, but its future looks promising.

  17. A Review of Current Regenerative Medicine Strategies that Utilize Nanotechnology to Treat Cartilage Damage

    PubMed Central

    Kumar, R.; Griffin, M.; Butler, P.E.

    2016-01-01

    Background: Cartilage is an important tissue found in a variety of anatomical locations. Damage to cartilage is particularly detrimental, owing to its intrinsically poor healing capacity. Current reconstructive options for cartilage repair are limited, and alternative approaches are required. Biomaterial science and Tissue engineering are multidisciplinary areas of research that integrate biological and engineering principles for the purpose of restoring premorbid tissue function. Biomaterial science traditionally focuses on the replacement of diseased or damaged tissue with implants. Conversely, tissue engineering utilizes porous biomimetic scaffolds, containing cells and bioactive molecules, to regenerate functional tissue. However, both paradigms feature several disadvantages. Faced with the increasing clinical burden of cartilage defects, attention has shifted towards the incorporation of Nanotechnology into these areas of regenerative medicine. Methods: Searches were conducted on Pubmed using the terms “cartilage”, “reconstruction”, “nanotechnology”, “nanomaterials”, “tissue engineering” and “biomaterials”. Abstracts were examined to identify articles of relevance, and further papers were obtained from the citations within. Results: The content of 96 articles was ultimately reviewed. The literature yielded no studies that have progressed beyond in vitro and in vivo experimentation. Several limitations to the use of nanomaterials to reconstruct damaged cartilage were identified in both the tissue engineering and biomaterial fields. Conclusion: Nanomaterials have unique physicochemical properties that interact with biological systems in novel ways, potentially opening new avenues for the advancement of constructs used to repair cartilage. However, research into these technologies is in its infancy, and clinical translation remains elusive. PMID:28217211

  18. Tissue Engineering and Regenerative Medicine: Semantic Considerations for an Evolving Paradigm

    PubMed Central

    Katari, Ravi; Peloso, Andrea; Orlando, Giuseppe

    2015-01-01

    Tissue engineering (TE) and regenerative medicine (RM) are rapidly evolving fields that are often obscured by a dense cloud of hype and commercialization potential. We find, in the literature and general commentary, that several of the associated terms are casually referenced in varying contexts that ultimately result in the blurring of the distinguishing boundaries which define them. “TE” and “RM” are often used interchangeably, though some experts vehemently argue that they, in fact, represent different conceptual entities. Nevertheless, contemporary scientists have a general idea of the experiments and milestones that can be classified within either or both categories. Given the groundbreaking achievements reported within the past decade and consequent watershed potential of this field, we feel that it would be useful to properly contextualize these terms semantically and historically. In this concept paper, we explore the various definitions proposed in the literature and emphasize that ambiguous terminology can lead to misplaced apprehension. We assert that the central motifs of both concepts have existed within the surgical sciences long before their appearance as terms in the scientific literature. PMID:25629029

  19. A Review of Current Regenerative Medicine Strategies that Utilize Nanotechnology to Treat Cartilage Damage.

    PubMed

    Kumar, R; Griffin, M; Butler, P E

    2016-01-01

    Cartilage is an important tissue found in a variety of anatomical locations. Damage to cartilage is particularly detrimental, owing to its intrinsically poor healing capacity. Current reconstructive options for cartilage repair are limited, and alternative approaches are required. Biomaterial science and Tissue engineering are multidisciplinary areas of research that integrate biological and engineering principles for the purpose of restoring premorbid tissue function. Biomaterial science traditionally focuses on the replacement of diseased or damaged tissue with implants. Conversely, tissue engineering utilizes porous biomimetic scaffolds, containing cells and bioactive molecules, to regenerate functional tissue. However, both paradigms feature several disadvantages. Faced with the increasing clinical burden of cartilage defects, attention has shifted towards the incorporation of Nanotechnology into these areas of regenerative medicine. Searches were conducted on Pubmed using the terms "cartilage", "reconstruction", "nanotechnology", "nanomaterials", "tissue engineering" and "biomaterials". Abstracts were examined to identify articles of relevance, and further papers were obtained from the citations within. The content of 96 articles was ultimately reviewed. The literature yielded no studies that have progressed beyond in vitro and in vivo experimentation. Several limitations to the use of nanomaterials to reconstruct damaged cartilage were identified in both the tissue engineering and biomaterial fields. Nanomaterials have unique physicochemical properties that interact with biological systems in novel ways, potentially opening new avenues for the advancement of constructs used to repair cartilage. However, research into these technologies is in its infancy, and clinical translation remains elusive.

  20. National Institutes of Health: a catalyst in advancing regenerative medicine science into practice.

    PubMed

    Rao, Mahendra

    2015-05-01

    The stem cell domain of the regenerative medicine field has seen fundamental changes initiated by seminal discoveries in cell biology, genetic engineering, and whole genome sequencing. Many of these discoveries were funded in part by the National Institutes of Health (NIH), and the NIH remains a leader in supporting research in the United States. However, as the field has developed, the NIH has responded proactively to identify roadblocks and to develop solutions that will accelerate translation of basic discoveries to the clinical setting. These activities range from organizing specialized workshops and coordinating activities among international organizations and the different arms of the government to funding small-scale industry. In addition, the NIH has been a key driver in providing needed infrastructure in areas in which the private sector has been unable to, or does not believe it can, invest. These activities of the NIH are as important as its traditional funding role, and I believe they have contributed to the innovation and rapid pace of discovery in this field.

  1. Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization.

    PubMed

    Birlea, Stanca A; Costin, Gertrude-E; Roop, Dennis R; Norris, David A

    2017-07-01

    Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation. © 2016 Wiley Periodicals, Inc.

  2. Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine

    PubMed Central

    Rennie, Kerry; Gruslin, Andrée; Hengstschläger, Markus; Pei, Duanqing; Cai, Jinglei; Nikaido, Toshio; Bani-Yaghoub, Mahmud

    2012-01-01

    The amniotic membrane (AM) and amniotic fluid (AF) have a long history of use in surgical and prenatal diagnostic applications, respectively. In addition, the discovery of cell populations in AM and AF which are widely accessible, nontumorigenic and capable of differentiating into a variety of cell types has stimulated a flurry of research aimed at characterizing the cells and evaluating their potential utility in regenerative medicine. While a major focus of research has been the use of amniotic membrane and fluid in tissue engineering and cell replacement, AM- and AF-derived cells may also have capabilities in protecting and stimulating the repair of injured tissues via paracrine actions, and acting as vectors for biodelivery of exogenous factors to treat injury and diseases. Much progress has been made since the discovery of AM and AF cells with stem cell characteristics nearly a decade ago, but there remain a number of problematic issues stemming from the inherent heterogeneity of these cells as well as inconsistencies in isolation and culturing methods which must be addressed to advance the field towards the development of cell-based therapies. Here, we provide an overview of the recent progress and future perspectives in the use of AM- and AF-derived cells for therapeutic applications. PMID:23093978

  3. On recent advances in human engineering Provocative trends in embryology, genetics, and regenerative medicine.

    PubMed

    Anton, Roman

    2016-01-01

    Advances in embryology, genetics, and regenerative medicine regularly attract attention from scientists, scholars, journalists, and policymakers, yet implications of these advances may be broader than commonly supposed. Laboratories culturing human embryos, editing human genes, and creating human-animal chimeras have been working along lines that are now becoming intertwined. Embryogenic methods are weaving traditional in vivo and in vitro distinctions into a new "in vivitro" (in life in glass) fabric. These and other methods known to be in use or thought to be in development promise soon to bring society to startling choices and discomfiting predicaments, all in a global effort to supply reliably rejuvenating stem cells, to grow immunologically non-provocative replacement organs, and to prevent, treat, cure, or even someday eradicate diseases having genetic or epigenetic mechanisms. With humanity's human-engineering era now begun, procedural prohibitions, funding restrictions, institutional controls, and transparency rules are proving ineffective, and business incentives are migrating into the most basic life-sciences inquiries, wherein lie huge biomedical potentials and bioethical risks. Rights, health, and heritage are coming into play with bioethical presumptions and formal protections urgently needing reassessment.

  4. Concise review: tailoring bioengineered scaffolds for stem cell applications in tissue engineering and regenerative medicine.

    PubMed

    Cosson, Steffen; Otte, Ellen A; Hezaveh, Hadi; Cooper-White, Justin J

    2015-02-01

    The potential for the clinical application of stem cells in tissue regeneration is clearly significant. However, this potential has remained largely unrealized owing to the persistent challenges in reproducibly, with tight quality criteria, and expanding and controlling the fate of stem cells in vitro and in vivo. Tissue engineering approaches that rely on reformatting traditional Food and Drug Administration-approved biomedical polymers from fixation devices to porous scaffolds have been shown to lack the complexity required for in vitro stem cell culture models or translation to in vivo applications with high efficacy. This realization has spurred the development of advanced mimetic biomaterials and scaffolds to increasingly enhance our ability to control the cellular microenvironment and, consequently, stem cell fate. New insights into the biology of stem cells are expected to eventuate from these advances in material science, in particular, from synthetic hydrogels that display physicochemical properties reminiscent of the natural cell microenvironment and that can be engineered to display or encode essential biological cues. Merging these advanced biomaterials with high-throughput methods to systematically, and in an unbiased manner, probe the role of scaffold biophysical and biochemical elements on stem cell fate will permit the identification of novel key stem cell behavioral effectors, allow improved in vitro replication of requisite in vivo niche functions, and, ultimately, have a profound impact on our understanding of stem cell biology and unlock their clinical potential in tissue engineering and regenerative medicine.

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

    DOE PAGES

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

    2015-04-01

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

  6. Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine.

    PubMed

    Polymeri, A; Giannobile, W V; Kaigler, D

    2016-11-01

    Bone marrow stromal stem cells (BMSCs) are adult multipotent cells, which have the potential to differentiate into cell types of mesodermal origin, namely osteocytes, adipocytes, and chondrocytes. Due to their accessibility and expansion potential, BMSCs have historically held therapeutic promise in tissue engineering and regenerative medicine applications. More recently, it has been demonstrated that not only can bone marrow stromal stem cells directly participate in tissue regeneration, but they also have the capacity to migrate to distant sites of tissue injury, where they can participate in tissue repair either directly through their differentiation or indirectly through paracrine mechanisms. Additionally, they can elicit various immunomodulatory signals, which can attenuate the inflammatory and immune responses. As such, bone marrow stromal stem cells have been explored clinically for treatment of a wide variety of different conditions including bone defects, graft-vs.-host disease, cardiovascular diseases, autoimmune diseases, diabetes, neurological diseases, and liver and kidney diseases. This review provides an overview of current clinical applications of bone marrow stromal stem cells and discusses their therapeutic properties, while also addressing limitations of their use. PubMed, Ovid, and Google Scholar online databases were searched using several keywords, including "stem cells", "tissue engineering", tissue regeneration" and "clinical trials". Additionally, Clinical trials.gov was used to locate completed clinical trials using bone marrow derived stem cells.

  7. Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine

    PubMed Central

    Atala, Anthony; Irvine, Darrell J.; Moses, Marsha; Shaunak, Sunil

    2013-01-01

    One of the major challenges in the field of regenerative medicine is how to optimize tissue regeneration in the body by therapeutically manipulating its natural ability to form scar at the time of injury or disease. It is often the balance between tissue regeneration, a process that is activated at the onset of disease, and scar formation, which develops as a result of the disease process that determines the ability of the tissue or organ to be functional. Using biomaterials as scaffolds often can provide a “bridge” for normal tissue edges to regenerate over small distances, usually up to 1 cm. Larger tissue defect gaps typically require both scaffolds and cells for normal tissue regeneration to occur without scar formation. Various strategies can help to modulate the scar response and can potentially enhance tissue regeneration. Understanding the mechanistic basis of such multivariate interactions as the scar microenvironment, the immune system, extracellular matrix, and inflammatory cytokines may enable the design of tissue engineering and wound healing strategies that directly modulate the healing response in a manner favorable to regeneration. PMID:24241586

  8. Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.

    PubMed

    Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul; Vrana, Nihal Engin

    2014-01-01

    In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

  9. Mathematical Models of Pluripotent Stem Cells: At the Dawn of Predictive Regenerative Medicine.

    PubMed

    Pir, Pınar; Le Novère, Nicolas

    2016-01-01

    Regenerative medicine, ranging from stem cell therapy to organ regeneration, is promising to revolutionize treatments of diseases and aging. These approaches require a perfect understanding of cell reprogramming and differentiation. Predictive modeling of cellular systems has the potential to provide insights about the dynamics of cellular processes, and guide their control. Moreover in many cases, it provides alternative to experimental tests, difficult to perform for practical or ethical reasons. The variety and accuracy of biological processes represented in mathematical models grew in-line with the discovery of underlying molecular mechanisms. High-throughput data generation led to the development of models based on data analysis, as an alternative to more established modeling based on prior mechanistic knowledge. In this chapter, we give an overview of existing mathematical models of pluripotency and cell fate, to illustrate the variety of methods and questions. We conclude that current approaches are yet to overcome a number of limitations: Most of the computational models have so far focused solely on understanding the regulation of pluripotency, and the differentiation of selected cell lineages. In addition, models generally interrogate only a few biological processes. However, a better understanding of the reprogramming process leading to ESCs and iPSCs is required to improve stem-cell therapies. One also needs to understand the links between signaling, metabolism, regulation of gene expression, and the epigenetics machinery.

  10. Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization

    PubMed Central

    Birlea, Stanca A.; Costin, Gertrude-E.; Roop, Dennis R.; Norris, David A.

    2017-01-01

    Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation. PMID:28029168

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-03-01

    In the last two decades, regenerative medicine has shown the potential for "bench-to-bedside" translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using "natural tissue" scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immunosuppression. This review describes recent advances in the engineering of several key tissues and organs. © 2010 The Authors. Transplant International © 2010 European Society for Organ Transplantation.

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

    SciTech Connect

    Martino, Mikael M.; Brkic, Sime; Bovo, Emmanuela; Burger, Maximilian; Schaefer, Dirk J.; Wolff, Thomas; Gurke, Lorenz; Briquez, Priscilla S.; Larsson, Hans M.; Gianni-Barrera, Roberto; Hubbell, Jeffrey A.; Banfi, Andrea

    2015-04-01

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

  14. Novel magnetic indenter for rheological analysis of thin biological sheet for regenerative medicine.

    PubMed

    Kageshima, Masami; Maruyama, Toshiro; Akama, Tomoya; Nakamura, Tomoyuki

    2016-07-01

    A novel method is proposed for analyzing the mechanical properties of a thin sheet of cells or extracellular matrix cultured for regenerative medicine. A steel sphere is mounted onto the center of the sheet sample, placed over a circular aperture, and a loading force is exerted via an electromagnet with well-regulated current while the displacement of the sample center is optically detected. Details of the instrument and its performance are described. Loading and unloading experiment with stepwise magnetic force revealed that creep response of each of the cell sheet and matrix sheet can be expressed as a combination of a quasi-instantaneous deformation and two delayed elastic responses having different retardation times. The retardation time exhibited an increasing trend with the loading force. Close analysis of loading-force dependence and reversibility of the derived mechanical parameters revealed that these deformation modes are not independent but flexibly switches to each other depending on load magnitude and loading history. The cell sheet sample exhibited remarkable irreversibility between loading and unloading responses, which is attributed to response of the live cells to the sustained loading.

  15. A showcase of bench-to-bedside regenerative medicine at the 2010 ASNTR.

    PubMed

    Eve, David J; Borlongan, Cesar V; Sanberg, Paul R

    2011-01-01

    Insight into the expanding themes of regenerative medicine is provided by the American Society for Neural Therapy and Repair's annual meeting. The 17th meeting covered a wide range of neurodegenerative disorders, exploring methods to elucidate the currently unknown mechanisms behind the disorders, as well as possible treatments ranging from the use of growth factors, gene therapy to cell transplantation. The importance of growth factors, both as a contributing factor to a disease and as a possible treatment either solo, or as a consequence of, or in conjunction with, stem cell therapy, was highlighted. The potential for viral vectors was also explored either for cells prior to transplantation or as a direct treatment regime into the brain itself. Identification of biomarkers that would allow early detection of a disease is an important factor in our fight against disease. The ability to now perform whole genome analysis and biomolecular profiling provides hope that such markers could be identified which not only could identify this likely to suffer from a disorder but also could allow its progress to be monitored. A few preclinical and clinical cell transplantation trials were also introduced as potential areas of followup in the years to come.

  16. A Showcase of Bench-to-Bedside Regenerative Medicine at the 2010 ASNTR

    PubMed Central

    Eve, David J.; Borlongan, Cesar V.; Sanberg, Paul R.

    2011-01-01

    Insight into the expanding themes of regenerative medicine is provided by the American Society for Neural Therapy and Repair's annual meeting. The 17th meeting covered a wide range of neurodegenerative disorders, exploring methods to elucidate the currently unknown mechanisms behind the disorders, as well as possible treatments ranging from the use of growth factors, gene therapy to cell transplantation. The importance of growth factors, both as a contributing factor to a disease and as a possible treatment either solo, or as a consequence of, or in conjunction with, stem cell therapy, was highlighted. The potential for viral vectors was also explored either for cells prior to transplantation or as a direct treatment regime into the brain itself. Identification of biomarkers that would allow early detection of a disease is an important factor in our fight against disease. The ability to now perform whole genome analysis and biomolecular profiling provides hope that such markers could be identified which not only could identify this likely to suffer from a disorder but also could allow its progress to be monitored. A few preclinical and clinical cell transplantation trials were also introduced as potential areas of followup in the years to come. PMID:22125442

  17. Novel magnetic indenter for rheological analysis of thin biological sheet for regenerative medicine

    NASA Astrophysics Data System (ADS)

    Kageshima, Masami; Maruyama, Toshiro; Akama, Tomoya; Nakamura, Tomoyuki

    2016-07-01

    A novel method is proposed for analyzing the mechanical properties of a thin sheet of cells or extracellular matrix cultured for regenerative medicine. A steel sphere is mounted onto the center of the sheet sample, placed over a circular aperture, and a loading force is exerted via an electromagnet with well-regulated current while the displacement of the sample center is optically detected. Details of the instrument and its performance are described. Loading and unloading experiment with stepwise magnetic force revealed that creep response of each of the cell sheet and matrix sheet can be expressed as a combination of a quasi-instantaneous deformation and two delayed elastic responses having different retardation times. The retardation time exhibited an increasing trend with the loading force. Close analysis of loading-force dependence and reversibility of the derived mechanical parameters revealed that these deformation modes are not independent but flexibly switches to each other depending on load magnitude and loading history. The cell sheet sample exhibited remarkable irreversibility between loading and unloading responses, which is attributed to response of the live cells to the sustained loading.

  18. Tooth regeneration: a revolution in stomatology and evolution in regenerative medicine

    PubMed Central

    Yildirim, Sibel; Fu, Susan Y; Kim, Keith; Zhou, Hong; Lee, Chang Hun; Li, Ang; Kim, Sahng Gyoon; Wang, Shuang; Mao, Jeremy J

    2011-01-01

    A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated? Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth? If not, what are the therapeutically viable sources of stem cells for tooth regeneration? Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration? How can regenerated teeth be economically competitive with dental implants? Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide? This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration: repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes. PMID:21789959

  19. Cell-derived matrices for tissue engineering and regenerative medicine applications1

    PubMed Central

    Fitzpatrick, Lindsay E.; McDevitt, Todd C.

    2014-01-01

    The development and application of decellularized extracellular matrices (ECM) has grown rapidly in the fields of cell biology, tissue engineering and regenerative medicine in recent years. Similar to decellularized tissues and whole organs, cell-derived matrices (CDMs) represent bioactive, biocompatible materials consisting of a complex assembly of fibrillar proteins, matrix macromolecules and associated growth factors that often recapitulate, at least to some extent, the composition and organization of native ECM microenvironments. The unique ability to engineer CDMs de novo based on cell source and culture methods makes them an attractive alternative to conventional allogeneic and xenogeneic tissue-derived matrices that are currently harvested from cadaveric sources, suffer from inherent heterogeneity, and have limited ability for customization. Although CDMs have been investigated for a number of biomedical applications, including adhesive cell culture substrates, synthetic scaffold coatings, and tissue engineered products, such as heart valves and vascular grafts, the state of the field is still at a relatively nascent stage of development. In this review, we provide an overview of the various applications of CDM and discuss successes to date, current limitations and future directions. PMID:25530850

  20. Tubular Tissues and Organs of Human Body--Challenges in Regenerative Medicine.

    PubMed

    Góra, Aleksander; Pliszka, Damian; Mukherjee, Shayanti; Ramakrishna, Seeram

    2016-01-01

    Tissue engineering of tubular organs such as the blood vessel, trachea gastrointestinal tract, urinary tract are of the great interest due to the high amount of surgeries performed annually on those organs. Development in tissue engineering in recent years and promising results, showed need to investigate more complex constructs that need to be designed in special manner. Stent technology remain the most widely used procedure to restore functions of tubular tissues after cancer treatment, or after organ removal due to traumatic accidents. Tubular structures like blood vessels, intestines, and trachea have to work in specific environment at the boundary of the liquids, solids or air and surrounding tissues and ensure suitable separation between them. This brings additional challenges in tissue engineering science in order to construct complete organs by using combinations of various cells along with the support material systems. Here we give a comprehensive review of the tubular structures of the human body, in perspective of the current methods of treatment and progress in regenerative medicine that aims to develop fully functioning organs of tubular shape. Extensive analysis of the available literature has been done focusing on materials and methods of creations of such organs. This work describes the attempts to incorporate growth factors and drugs within the scaffolds to ensure localized drug release and enhance vascularization of the organ by attracting blood vessels to the site of implantation.

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

    SciTech Connect

    Martino, Mikael M.; Brkic, Sime; Bovo, Emmanuela; Burger, Maximilian; Schaefer, Dirk J.; Wolff, Thomas; Gurke, Lorenz; Briquez, Priscilla S.; Larsson, Hans M.; Gianni-Barrera, Roberto; Hubbell, Jeffrey A.; Banfi, Andrea

    2015-04-01

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

  2. Fat on sale: role of adipose-derived stem cells as anti-fibrosis agent in regenerative medicine.

    PubMed

    Gupta, Manoj K; Ajay, Amrendra Kumar

    2015-12-01

    The potential use of stem cells for cell-based tissue repair and regeneration offers alternative therapeutic strategies for various diseases. Adipose-derived stem cells (ADSCs) have emerged as a promising source of stem cells suitable for transplantation in regenerative medicine and wound repair. A recent publication in Stem Cell Research & Therapy by Zhang and colleagues reports a new finding about the anti-fibrosis role of ADSCs and conditioned media derived from them on hypertrophic scar formation in vivo.

  3. Correction: Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine.

    PubMed

    Curran, Judith M; Stokes, Robert; Irvine, Eleanore; Graham, Duncan; Amro, N A; Sanedrin, R G; Jamil, H; Hunt, John A

    2017-06-13

    Correction for 'Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine' by Judith M. Curran et al., Lab Chip, 2010, 10, 1662-1670.

  4. Employment of the Triple Helix concept for development of regenerative medicine applications based on human pluripotent stem cells.

    PubMed

    Sartipy, Peter; Björquist, Petter

    2014-01-01

    Using human pluripotent stem cells as a source to generate differentiated progenies for regenerative medicine applications has attracted substantial interest during recent years. Having the capability to produce large quantities of human cells that can replace damaged tissue due to disease or injury opens novel avenues for relieving symptoms and also potentially offers cures for many severe human diseases. Although tremendous advancements have been made, there is still much research and development left before human pluripotent stem cell derived products can be made available for cell therapy applications. In order to speed up the development processes, we argue strongly in favor of cross-disciplinary collaborative efforts which have many advantages, especially in a relatively new field such as regenerative medicine based on human pluripotent stem cells. In this review, we aim to illustrate how some of the hurdles for bringing human pluripotent stem cell derivatives from bench-to-bed can be effectively addressed through the establishment of collaborative programs involving academic institutions, biotech industries, and pharmaceutical companies. By taking advantage of the strengths from each organization, innovation and productivity can be maximized from a resource perspective and thus, the chances of successfully bringing novel regenerative medicine treatment options to patients increase.

  5. Osteoblastic/Cementoblastic and Neural Differentiation of Dental Stem Cells and Their Applications to Tissue Engineering and Regenerative Medicine

    PubMed Central

    Kim, Byung-Chul; Bae, Hojae; Kwon, Il-Keun; Lee, Eun-Jun; Park, Jae-Hong

    2012-01-01

    Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine. PMID:22224548

  6. Employment of the Triple Helix concept for development of regenerative medicine applications based on human pluripotent stem cells

    PubMed Central

    2014-01-01

    Using human pluripotent stem cells as a source to generate differentiated progenies for regenerative medicine applications has attracted substantial interest during recent years. Having the capability to produce large quantities of human cells that can replace damaged tissue due to disease or injury opens novel avenues for relieving symptoms and also potentially offers cures for many severe human diseases. Although tremendous advancements have been made, there is still much research and development left before human pluripotent stem cell derived products can be made available for cell therapy applications. In order to speed up the development processes, we argue strongly in favor of cross-disciplinary collaborative efforts which have many advantages, especially in a relatively new field such as regenerative medicine based on human pluripotent stem cells. In this review, we aim to illustrate how some of the hurdles for bringing human pluripotent stem cell derivatives from bench-to-bed can be effectively addressed through the establishment of collaborative programs involving academic institutions, biotech industries, and pharmaceutical companies. By taking advantage of the strengths from each organization, innovation and productivity can be maximized from a resource perspective and thus, the chances of successfully bringing novel regenerative medicine treatment options to patients increase. PMID:24872863

  7. Development of a noninvasive multifunctional measurement method using nanosecond pulsed laser for evaluation of regenerative medicine for articular cartilage

    NASA Astrophysics Data System (ADS)

    Ishihara, Miya; Sato, Masato; Kaneshiro, Nagatoshi; Mitani, Genya; Sato, Shunichi; Ishihara, Masayuki; Mochida, Joji; Kikuchi, Makoto

    2006-02-01

    We demonstrated the capability of a photoacoustic method for viscoelastic measurement. The measurement method has already proved to be useful for evaluation of regenerative medicine of articular cartilage. However, characterization of the extracellular matrix as well as determination of the viscoelastic property should be carried out for evaluation of regenerative medicine because the extracellular matrix plays an important role. We therefore developed a method for characterization of the extracellular matrix that can be performed simultaneously with the photoacoustic measurement. Since collagen molecules, which are the major contents of the cartilage extracellular matrix, are well known as endogenous fluorescent molecules, it is possible that fluorescence measurement will enable characterization of the extracellular matrix. Third harmonic Q-switched Nd:YAG laser pulses were used as an excitation light source. The time-resolved fluorescence spectroscopy was obtained by using a photonic multi-channel analyzer. Tissue-engineered cartilages cultured under different conditions for various periods were used as samples. Different culture conditions resulted in different extracellular matrix formations. There were significant differences in the measured fluorescent parameters among the culture conditions of cartilage because chondrocytes produce a specific extracellular matrix depending on its culture condition. The specific extracellular matrix contained a specific type of collagen such as collagen type I or type II, which each have specific fluorescent features. Thus, the fluorescent parameters enabled characterization of synthesis of cartilage-associated extracellular matrix. Therefore, the combination of fluorescence and photoacoustic measurement is expected to become a useful evaluation method in regenerative medicine.

  8. Identifying viable regulatory and innovation pathways for regenerative medicine: a case study of cultured red blood cells.

    PubMed

    Mittra, J; Tait, J; Mastroeni, M; Turner, M L; Mountford, J C; Bruce, K

    2015-01-25

    The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5-10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field.

  9. Osteoblastic/cementoblastic and neural differentiation of dental stem cells and their applications to tissue engineering and regenerative medicine.

    PubMed

    Kim, Byung-Chul; Bae, Hojae; Kwon, Il-Keun; Lee, Eun-Jun; Park, Jae-Hong; Khademhosseini, Ali; Hwang, Yu-Shik

    2012-06-01

    Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine.

  10. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    NASA Astrophysics Data System (ADS)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  11. Biological computational approaches: new hopes to improve (re)programming robustness, regenerative medicine and cancer therapeutics.

    PubMed

    Ebrahimi, Behnam

    2016-01-01

    Hundreds of transcription factors (TFs) are expressed and work in each cell type, but the identity of the cells is defined and maintained through the activity of a small number of core TFs. Existing reprogramming strategies predominantly focus on the ectopic expression of core TFs of an intended fate in a given cell type regardless of the state of native/somatic gene regulatory networks (GRNs) of the starting cells. Interestingly, an important point is that how much products of the reprogramming, transdifferentiation and differentiation (programming) are identical to their in vivo counterparts. There is evidence that shows that direct fate conversions of somatic cells are not complete, with target cell identity not fully achieved. Manipulation of core TFs provides a powerful tool for engineering cell fate in terms of extinguishment of native GRNs, the establishment of a new GRN, and preventing installation of aberrant GRNs. Conventionally, core TFs are selected to convert one cell type into another mostly based on literature and the experimental identification of genes that are differentially expressed in one cell type compared to the specific cell types. Currently, there is not a universal standard strategy for identifying candidate core TFs. Remarkably, several biological computational platforms are developed, which are capable of evaluating the fidelity of reprogramming methods and refining existing protocols. The current review discusses some deficiencies of reprogramming technologies in the production of a pure population of authentic target cells. Furthermore, it reviews the role of computational approaches (e.g. CellNet, KeyGenes, Mogrify, etc.) in improving (re)programming methods and consequently in regenerative medicine and cancer therapeutics. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  12. Regenerative medicine provides alternative strategies for the treatment of anal incontinence.

    PubMed

    Gräs, Søren; Tolstrup, Cæcilie Krogsgaard; Lose, Gunnar

    2017-03-01

    Anal incontinence is a common disorder but current treatment modalities are not ideal and the development of new treatments is needed. The aim of this review was to identify the existing knowledge of regenerative medicine strategies in the form of cellular therapies or bioengineering as a treatment for anal incontinence caused by anal sphincter defects. PubMed was searched for preclinical and clinical studies in English published from January 2005 to January 2016. Animal studies have demonstrated that cellular therapy in the form of local injections of culture-expanded skeletal myogenic cells stimulates repair of both acute and 2 - 4-week-old anal sphincter injuries. The results from a small clinical trial with ten patients and a case report support the preclinical findings. Animal studies have also demonstrated that local injections of mesenchymal stem cells stimulate repair of sphincter injuries, and a complex bioengineering strategy for creation and implantation of an intrinsically innervated internal anal sphincter construct has been successfully developed in a series of animal studies. Cellular therapies with myogenic cells and mesenchymal stem cells and the use of bioengineering technology to create an anal sphincter are new potential strategies to treat anal incontinence caused by anal sphincter defects, but the clinical evidence is extremely limited. The use of culture-expanded autologous skeletal myogenic cells has been most intensively investigated and several clinical trials were ongoing at the time of this report. The cost-effectiveness of such a therapy is an issue and muscle fragmentation is suggested as a simple alternative.

  13. In Vitro Generated Hepatocyte-Like Cells: A Novel Tool in Regenerative Medicine and Drug Discovery.

    PubMed

    Zakikhan, Kobra; Pournasr, Behshad; Vosough, Massoud; Nassiri-Asl, Marjan

    2017-01-01

    Hepatocyte-like cells (HLCs) are generated from either various human pluripotent stem cells (hPSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or direct cell conversion, mesenchymal stem cells as well as other stem cells like gestational tissues. They provide potential cell sources for biomedical applications. Liver transplantation is the gold standard treatment for the patients with end stage liver disease, but there are many obstacles limiting this process, like insufficient number of donated healthy livers. Meanwhile, the number of patients receiving a liver organ transplant for a better life is increasing. In this regard, HLCs may provide an adequate cell source to overcome these shortages. New molecular engineering approaches such as CRISPR/ Cas system applying in iPSCs technology provide the basic principles of gene correction for monogenic inherited metabolic liver diseases, as another application of HLCs. It has been shown that HLCs could replace primary human hepatocytes in drug discovery and hepatotoxicity tests. However, generation of fully functional HLCs is still a big challenge; several research groups have been trying to improve current differentiation protocols to achieve better HLCs according to morphology and function of cells. Large-scale generation of functional HLCs in bioreactors could make a new opportunity in producing enough hepatocytes for treating end-stage liver patients as well as other biomedical applications such as drug studies. In this review, regarding the biomedical value of HLCs, we focus on the current and efficient approaches for generating hepatocyte-like cells in vitro and discuss about their applications in regenerative medicine and drug discovery.

  14. Plasticity of human dental pulp stromal cells with bioengineering platforms: a versatile tool for regenerative medicine.

    PubMed

    Barachini, Serena; Danti, Serena; Pacini, Simone; D'Alessandro, Delfo; Carnicelli, Vittoria; Trombi, Luisa; Moscato, Stefania; Mannari, Claudio; Cei, Silvia; Petrini, Mario

    2014-12-01

    In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to their characteristics in common with other mesenchymal stem cells, in addition to the ease with which they can be harvested. In this study, we demonstrated that the isolation of DPSCs from third molar teeth of healthy individuals allowed the recovery of dental mesenchymal stem cells that showed self-renewal and multipotent differentiation capability. DPSCs resulted positive for CD73, CD90, CD105, STRO-1, negative for CD34, CD45, CD14 and were able to differentiate into osteogenic and chondrogenic cells. We also assayed the angiogenic potential of DPSCs, their capillary tube-like formation was assessed using an in vitro angiogenesis assay and the uptake of acetylated low-density lipoprotein was measured as a marker of endothelial function. Based on these results, DPSCs were capable of differentiating into cells with phenotypic and functional features of endothelial cells. Furthermore, this study investigated the growth and differentiation of human DPSCs under a variety of bioengineering platforms, such as low frequency ultrasounds, tissue engineering and nanomaterials. DPSCs showed an enhanced chondrogenic differentiation under ultrasound application. Moreover, DPSCs were tested on different scaffolds, poly(vinyl alcohol)/gelatin (PVA/G) sponges and human plasma clots. We showed that both PVA/G and human plasma clot are suitable scaffolds for adhesion, growth and differentiation of DPSCs toward osteoblastic lineages. Finally, we evaluated the interactions of DPSCs with a novel class of nanomaterials, namely boron nitride nanotubes (BNNTs). From our investigation, DPSCs have appeared as a highly versatile cellular tool to be employed in regenerative medicine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. In Vitro Generated Hepatocyte-Like Cells: A Novel Tool in Regenerative Medicine and Drug Discovery

    PubMed Central

    Zakikhan, Kobra; Pournasr, Behshad; Vosough, Massoud; Nassiri-Asl, Marjan

    2017-01-01

    Hepatocyte-like cells (HLCs) are generated from either various human pluripotent stem cells (hPSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or direct cell conversion, mesenchymal stem cells as well as other stem cells like gestational tissues. They provide potential cell sources for biomedical applications. Liver transplantation is the gold standard treatment for the patients with end stage liver disease, but there are many obstacles limiting this process, like insufficient number of donated healthy livers. Meanwhile, the number of patients receiving a liver organ transplant for a better life is increasing. In this regard, HLCs may provide an adequate cell source to overcome these shortages. New molecular engineering approaches such as CRISPR/ Cas system applying in iPSCs technology provide the basic principles of gene correction for monogenic inherited metabolic liver diseases, as another application of HLCs. It has been shown that HLCs could replace primary human hepatocytes in drug discovery and hepatotoxicity tests. However, generation of fully functional HLCs is still a big challenge; several research groups have been trying to improve current differentiation protocols to achieve better HLCs according to morphology and function of cells. Large-scale generation of functional HLCs in bioreactors could make a new opportunity in producing enough hepatocytes for treating end-stage liver patients as well as other biomedical applications such as drug studies. In this review, regarding the biomedical value of HLCs, we focus on the current and efficient approaches for generating hepatocyte-like cells in vitro and discuss about their applications in regenerative medicine and drug discovery. PMID:28670513

  16. The Hippo Pathway and YAP/TAZ-TEAD Protein-Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment.

    PubMed

    Santucci, Matteo; Vignudelli, Tatiana; Ferrari, Stefania; Mor, Marco; Scalvini, Laura; Bolognesi, Maria Laura; Uliassi, Elisa; Costi, Maria Paola

    2015-06-25

    The Hippo pathway is an important organ size control signaling network and the major regulatory mechanism of cell-contact inhibition. Yes associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are its targets and terminal effectors: inhibition of the pathway promotes YAP/TAZ translocation to the nucleus, where they interact with transcriptional enhancer associate domain (TEAD) transcription factors and coactivate the expression of target genes, promoting cell proliferation. Defects in the pathway can result in overgrowth phenotypes due to deregulation of stem-cell proliferation and apoptosis; members of the pathway are directly involved in cancer development. The pharmacological regulation of the pathway might be useful in cancer prevention, treatment, and regenerative medicine applications; currently, a few compounds can selectively modulate the pathway. In this review, we present an overview of the Hippo pathway, the sequence and structural analysis of YAP/TAZ, the known pharmacological modulators of the pathway, especially those targeting YAP/TAZ-TEAD interaction.

  17. Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how?

    PubMed

    de Windt, Tommy S; Hendriks, Jeanine A A; Zhao, Xing; Vonk, Lucienne A; Creemers, Laura B; Dhert, Wouter J A; Randolph, Mark A; Saris, Daniel B F

    2014-06-01

    Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartilage regeneration in vitro and in vivo. However, there is considerable debate regarding the mechanisms and cellular interactions that lead to chondrogenesis in these models. This review, which included 52 papers, provides a systematic overview of the data presented in the literature and tries to elucidate the mechanisms that lead to chondrogenesis in stem cell cocultures with cartilage cells. It could serve as a basis for research groups and clinicians aiming at designing and implementing combined cellular technologies for single-stage cartilage repair and treatment or prevention of OA.

  18. Current and future regenerative medicine — Principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    PubMed Central

    Koch, Thomas G.; Berg, Lise C.; Betts, Dean H.

    2009-01-01

    This paper provides a bird’s-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine. The understanding of equine stem cell biology, biofactors, and scaffolds, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering — cells, biological factors, and biomaterials — are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources. The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently in controlled clinical trials in equine patients to be regarded as evidence-based medicine. In the meantime, the medical mantra “do no harm” should prevail, and the application of stem cell-based therapies in the horse should be done critically and cautiously, and treatment outcomes (good and bad) should be recorded and reported. Stem cell and tissue engineering research in the horse has exciting comparative and equine specific perspectives that most likely will benefit the health of horses and humans. Controlled, well-designed studies are needed to move this new equine research field forward. PMID:19412395

  19. Identification, characterization and biological significance of very small embryonic-like stem cells (VSELs) in regenerative medicine.

    PubMed

    Feng, Guowei; Cui, Jian; Zheng, Yizhou; Han, Zhongchao; Xu, Yong; Li, Zongjin

    2012-07-01

    The progress of stem cell research, along with technological innovation, has brought researchers to focus on the potential role of stem cells in regenerative medicine. Ethical and technological issues have limited the applications of human embryonic stem cells (hESCs) in this field. As a promising candidate, very small embryonic-like stem cells (VSELs) express a multitude of pluripotent stem cell markers and demonstrate the ability to differentiate into three germ-layer lineages in vitro. Optimized methods for isolation and expansion of VSELs have aroused the scientific community's interest in use of this kind of cells for regenerative purposes. In this review, we will focus on the biological characteristics, as well as the potentiality and remaining challenges in clinical application of VSELs. Moreover, a comparison among VSELs and the other pluripotent stem cells will be illustrated to highlight the unique advantages of VSELs.

  20. Decellularized omentum as novel biologic scaffold for reconstructive surgery and regenerative medicine

    PubMed Central

    Porzionato, A.; Sfriso, M.M.; Macchi, V.; Rambaldo, A.; Lago, G.; Lancerotto, L.; Vindigni, V.; De Caro, R.

    2013-01-01

    Homologous tissues, such as adipose tissue, may be an interesting source of acellular scaffolds, maintaining a complex physiological three-dimensional (3D) structure, to be recellularized with autologous cells. The aim of the present work is to evaluate the possibility of obtaining homologous acellular scaffolds from decellularization of the omentum, which is known to have a complex vascular network. Adult rat and human omenta were treated with an adapted decellularization protocol involving mechanical rupture (freeze-thaw cycles), enzymatic digestion (trypsin, lipase, deoxyribonuclease, ribonuclease) and lipid extraction (2-propanol). Histological staining confirmed the effectiveness of decellularization, resulting in cell-free scaffolds with no residual cells in the matrix. The complex 3D networks of collagen (azan-Mallory), elastic fibers (Van Gieson), reticular fibers and glycosaminoglycans (PAS) were maintained, whereas Oil Red and Sudan stains showed the loss of lipids in the decellularized tissue. The vascular structures in the tissue were still visible, with preservation of collagen and elastic wall components and loss of endothelial (anti-CD31 and -CD34 immunohistochemistry) and smooth muscle (anti-alpha smooth muscle actin) cells. Fat-rich and well vascularized omental tissue may be decellularized to obtain complex 3D scaffolds preserving tissue architecture potentially suitable for recellularization. Further analyses are necessary to verify the possibility of recolonization of the scaffold by adipose-derived stem cells in vitro and then in vivo after re implantation, as already known for homologus implants in regenerative processes. PMID:23549463

  1. Key players in the immune response to biomaterial scaffolds for regenerative medicine.

    PubMed

    Chung, Liam; Maestas, David R; Housseau, Franck; Elisseeff, Jennifer H

    2017-05-15

    The compatibility of biomaterials is critical to their structural and biological function in medical applications. The immune system is the first responder to tissue trauma and to a biomaterial implant. The innate immune effector cells, most notably macrophages, play a significant role in the defense against foreign bodies and the formation of a fibrous capsule around synthetic implants. Alternatively, macrophages participate in the pro-regenerative capacity of tissue-derived biological scaffolds. Research is now elucidating the role of the adaptive immune system, and T cells in particular, in directing macrophage response to synthetic and biological materials. Here, we review basic immune cell types and discuss recent research on the role of the immune system in tissue repair and its potential relevance to scaffold design. We will also discuss new emerging immune cell types relevant to biomaterial responses and tissue repair. Finally, prospects for specifically targeting and modulating the immune response to biomaterial scaffolds for enhancing tissue repair and regeneration will be presented. Copyright © 2017. Published by Elsevier B.V.

  2. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery

    PubMed Central

    Singh, Vimal K.; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner. PMID:25699255

  3. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery.

    PubMed

    Singh, Vimal K; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner.

  4. Hurdles in tissue engineering/regenerative medicine product commercialization: a survey of North American academia and industry.

    PubMed

    Johnson, Peter C; Bertram, Timothy A; Tawil, Bill; Hellman, Kiki B

    2011-01-01

    The Tissue Engineering and Regenerative Medicine International Society-North America (TERMIS-NA) Industry Committee was formed in February 2009 to address the common roadblocks (i.e., hurdles) in the commercialization of tissue engineering/regenerative medicine products for its members. A semiquantitative online opinion survey instrument that delineated potentially sensitive hurdles to commercialization in each of the TERMIS constituency groups that generally participate in the stream of technology commercialization (academia, startup companies, development-stage companies, and established companies) was developed. The survey was opened to each of the 863 members of TERMIS-NA for a period of 5 weeks from October to November 2009. By its conclusion, 215 members (25%) had responded. Their proportionate numbers were closely representative of TERMIS-NA constituencies. The resulting data delineate what each group considers to be its most difficult and also its easiest hurdles in taking a technology to full product development. In addition, each group ranked its perception of the difficult and easy hurdles for all other groups, enabling an assessment of the degree of understanding between groups. The data depict not only critical hurdles in the path to commercialization at each stage in product development but also a variable understanding of perceptions of hurdles between groups. This assessment has provided the Industry Committee with activity foci needed to assist individual groups in the technology-commercialization stream. Moreover, the analysis suggests that enhanced communication between groups engaged in commercialization will be critical to the successful development of products in the tissue engineering/regenerative medicine sector.

  5. Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    PubMed

    Shtrichman, R; Germanguz, I; Itskovitz-Eldor, J

    2013-06-01

    Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.

  6. The Armed Forces Institute of Regenerative Medicine: a collaborative approach to Department of Defense-relevant research.

    PubMed

    Dean, Wendy

    2011-11-01

    The wars in Iraq and Afghanistan have resulted in the most severe survivable war injuries ever seen in prolonged conflict. The Armed Forces Institute of Regenerative Medicine (AFIRM) was conceived as a way to deliver solutions to the existing gaps in military trauma care. The AFIRM is a collaborative effort between the Department of Defense, academia and private industry to accelerate the development of critically needed technology for the treatment of severely wounded warriors, and to restore to meaningful form and function those who have followed orders into harm's way.

  7. Gene therapy for eye as regenerative medicine? Lessons from RPE65 gene therapy for Leber's Congenital Amaurosis.

    PubMed

    Rakoczy, Elizabeth P; Narfström, Kristina

    2014-11-01

    Recombinant virus mediated gene therapy of Leber's Congenital Amaurosis has provided a wide range of data on the utility of gene replacement therapy for recessive diseases. Studies to date demonstrate that gene therapy in the eye is safe and can result in long-term recovery of visual function, but they also highlight that further research is required to identify optimum intervention time-points, target populations and the compatibility of associate therapies. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 3D Biomaterial Microarrays for Regenerative Medicine: Current State-of-the-Art, Emerging Directions and Future Trends.

    PubMed

    Gaharwar, Akhilesh K; Arpanaei, Ayyoob; Andresen, Thomas L; Dolatshahi-Pirouz, Alireza

    2016-01-27

    Three dimensional (3D) biomaterial microarrays hold enormous promise for regenerative medicine because of their ability to accelerate the design and fabrication of biomimetic materials. Such tissue-like biomaterials can provide an appropriate microenvironment for stimulating and controlling stem cell differentiation into tissue-specific lineages. The use of 3D biomaterial microarrays can, if optimized correctly, result in a more than 1000-fold reduction in biomaterials and cells consumption when engineering optimal materials combinations, which makes these miniaturized systems very attractive for tissue engineering and drug screening applications.

  9. [Presentation of eponymous terms in forensic medicine].

    PubMed

    Nečas, P; Hejna, P

    2012-04-01

    The phenomenon of eponymous terms used in forensic medicine is described in the paper. Their linguistic basis, advantages and disadvantages for specialists or wider circles is discussed. Their spread in various language discourses is mentioned. A list of the most important eponymous terms in forensic medicine is the papers focus.

  10. Regenerative medicine for the treatment of spinal cord injury: more than just promises?

    PubMed Central

    Pêgo, Ana Paula; Kubinova, Sarka; Cizkova, Dasa; Vanicky, Ivo; Mar, Fernando Milhazes; Sousa, Mónica Mendes; Sykova, Eva

    2012-01-01

    Spinal cord injury triggers a complex set of events that lead to tissue healing without the restoration of normal function due to the poor regenerative capacity of the spinal cord. Nevertheless, current knowledge about the intrinsic regenerative ability of central nervous system axons, when in a supportive environment, has made the prospect of treating spinal cord injury a reality. Among the range of strategies under investigation, cell-based therapies offer the most promising results, due to the multifactorial roles that these cells can fulfil. However, the best cell source is still a matter of debate, as are clinical issues that include the optimal cell dose as well as the timing and route of administration. In this context, the role of biomaterials is gaining importance. These can not only act as vehicles for the administered cells but also, in the case of chronic lesions, can be used to fill the permanent cyst, thus creating a more favourable and conducive environment for axonal regeneration in addition to serving as local delivery systems of therapeutic agents to improve the regenerative milieu. Some of the candidate molecules for the future are discussed in view of the knowledge derived from studying the mechanisms that facilitate the intrinsic regenerative capacity of central nervous system neurons. The future challenge for the multidisciplinary teams working in the field is to translate the knowledge acquired in basic research into effective combinatorial therapies to be applied in the clinic. PMID:22805417

  11. Regenerative medicine for the treatment of spinal cord injury: more than just promises?

    PubMed

    Pêgo, Ana Paula; Kubinova, Sarka; Cizkova, Dasa; Vanicky, Ivo; Mar, Fernando Milhazes; Sousa, Mónica Mendes; Sykova, Eva

    2012-11-01

    Spinal cord injury triggers a complex set of events that lead to tissue healing without the restoration of normal function due to the poor regenerative capacity of the spinal cord. Nevertheless, current knowledge about the intrinsic regenerative ability of central nervous system axons, when in a supportive environment, has made the prospect of treating spinal cord injury a reality. Among the range of strategies under investigation, cell-based therapies offer the most promising results, due to the multifactorial roles that these cells can fulfil. However, the best cell source is still a matter of debate, as are clinical issues that include the optimal cell dose as well as the timing and route of administration. In this context, the role of biomaterials is gaining importance. These can not only act as vehicles for the administered cells but also, in the case of chronic lesions, can be used to fill the permanent cyst, thus creating a more favourable and conducive environment for axonal regeneration in addition to serving as local delivery systems of therapeutic agents to improve the regenerative milieu. Some of the candidate molecules for the future are discussed in view of the knowledge derived from studying the mechanisms that facilitate the intrinsic regenerative capacity of central nervous system neurons. The future challenge for the multidisciplinary teams working in the field is to translate the knowledge acquired in basic research into effective combinatorial therapies to be applied in the clinic.

  12. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

    PubMed Central

    Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C.; Nolta, Jan A.

    2015-01-01

    The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Significance Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it

  13. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine.

    PubMed

    Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C; Nolta, Jan A; Athanasiou, Kyriacos A

    2015-10-01

    The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides

  14. Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff.

    PubMed

    Meyer, Gretchen A; Ward, Samuel R

    2016-05-01

    Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in dev