Exploiting the Bioactive Properties of the Dentin-Pulp Complex in Regenerative Endodontics.

Science.gov (United States)

Smith, Anthony J; Duncan, Henry F; Diogenes, Anibal; Simon, Stephane; Cooper, Paul R

2016-01-01

The development of regenerative endodontic therapies offers exciting opportunities for future improvements in treatment outcomes. Advances in our understanding of regenerative events at the molecular and cellular levels are helping to underpin development of these therapies, although the various strategies differ in the translational challenges they pose. The identification of a variety of bioactive molecules, including growth factors, cytokines, chemokines, and matrix molecules, sequestered within dentin and dental pulp provides the opportunity to present key signaling molecules promoting reparative and regenerative events after injury. The protection of the biological activity of these molecules by mineral in dentin before their release allows a continuing supply of these molecules, while avoiding the short half-life and the non-human origin of exogenous molecules. The ready release of these bioactive molecules by the various tissue preparation agents, medicaments, and materials commonly used in endodontics highlights the opportunities for translational regenerative strategies exploiting these molecules with little change to existing clinical practice. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Free radical scavenging injectable hydrogels for regenerative therapy

Energy Technology Data Exchange (ETDEWEB)

Komeri, Remya [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State (India); Thankam, Finosh Gnanaprakasam [Dept. of Biomedical Sciences, Creighton University, 2500 California Plaza, Omaha NE68178 (United States); Muthu, Jayabalan, E-mail: mjayabalan52@gmail.com [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State (India)

2017-02-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. - Graphical abstract: Injectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application. - Highlights: • Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer

Free radical scavenging injectable hydrogels for regenerative therapy

International Nuclear Information System (INIS)

Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2017-01-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. - Graphical abstract: Injectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application. - Highlights: • Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer

Meeting the need for regenerative therapies I: target-based incidence and its relationship to U.S. spending, productivity, and innovation.

Science.gov (United States)

Parenteau, Nancy; Hardin-Young, Janet; Shannon, William; Cantini, Patrick; Russell, Alan

2012-04-01

Regenerative therapies possess high theoretical potential for medical advance yet their success as commercial therapeutics is still open to debate. Appropriate data on target opportunities that provide perspective and enable strategic decision making is necessary for both efficient and effective translation. Up until now, this data have been out of reach to research scientists and many start-up companies-the very groups currently looked to for the critical advance of these therapies. The target-based estimate of opportunity presented in this report demonstrates its importance in evaluating medical need and technology feasibility. In addition, analysis of U.S. research spending, productivity, and innovation reveals that U.S. basic research in this field would benefit from greater interdisciplinarity. Overcoming the barriers that currently prevent translation into high value therapies that are quickly clinically adopted requires simultaneous integration of engineering, science, business, and clinical practice. Achieving this integration is nontrivial.

Accelerating regenerative medicine: the Japanese experiment in ethics and regulation.

Science.gov (United States)

Lysaght, Tamra

2017-09-01

In 2014, the Japanese National Diet introduced new laws aimed at promoting the clinical translation of stem cells and regenerative medicine. The basic action of these laws is to allow the early introduction of regenerative medicine products into the Japanese market through an accelerated approval process, while providing patients with access to certain types of stem cell and cell-based therapies in the context of private clinical practice. While this framework appears to offer enormous opportunities for the translation of stem cell science, it raises ethical challenges that have not yet been fully explored. This paper critically analyzes this framework with respect to the prioritization of safety over clinical benefit, distributive justice and public trust in science and medicine. It is argued that the framework unfairly burdens patients and strained healthcare systems without any clear benefits, and may undermine the credibility of the regenerative medicine field as it emerges.

Regenerative Therapies for Diabetic Microangiopathy

Directory of Open Access Journals (Sweden)

Roberto Bassi

2012-01-01

Full Text Available Hyperglycaemia occurring in diabetes is responsible for accelerated arterial remodeling and atherosclerosis, affecting the macro- and the microcirculatory system. Vessel injury is mainly related to deregulation of glucose homeostasis and insulin/insulin-precursors production, generation of advanced glycation end-products, reduction in nitric oxide synthesis, and oxidative and reductive stress. It occurs both at extracellular level with increased calcium and matrix proteins deposition and at intracellular level, with abnormalities of intracellular pathways and increased cell death. Peripheral arterial disease, coronary heart disease, and ischemic stroke are the main causes of morbidity/mortality in diabetic patients representing a major clinical and economic issue. Pharmacological therapies, administration of growth factors, and stem cellular strategies are the most effective approaches and will be discussed in depth in this comprehensive review covering the regenerative therapies of diabetic microangiopathy.

Prospective regenerative medicine therapies for obstetric trauma-induced fecal incontinence.

Science.gov (United States)

Parmar, Nina; Kumar, Lalit; Emmanuel, Anton; Day, Richard M

2014-01-01

Fecal incontinence is a major public health issue that has yet to be adequately addressed. Obstetric trauma and injury to the anal sphincter muscles are the most common cause of fecal incontinence. New therapies are emerging aimed at repair or regeneration of sphincter muscle and restoration of continence. While regenerative medicine offers an attractive option for fecal incontinence there are currently no validated techniques using this approach. Although many challenges are yet to be resolved, the advent of regenerative medicine is likely to offer disruptive technologies to treat and possibly prevent the onset of this devastating condition. This article provides a review on regenerative medicine approaches for treating fecal incontinence and a critique of the current landscape in this area.

Regenerative medicine in otorhinolaryngology.

Science.gov (United States)

Wormald, J C R; Fishman, J M; Juniat, S; Tolley, N; Birchall, M A

2015-08-01

Tissue engineering using biocompatible scaffolds, with or without cells, can permit surgeons to restore structure and function following tissue resection or in cases of congenital abnormality. Tracheal regeneration has emerged as a spearhead application of these technologies, whilst regenerative therapies are now being developed to treat most other diseases within otolaryngology. A systematic review of the literature was performed using Ovid Medline and Ovid Embase, from database inception to 15 November 2014. A total of 561 papers matched the search criteria, with 76 fulfilling inclusion criteria. Articles were predominantly pre-clinical animal studies, reflecting the current status of research in this field. Several key human research articles were identified and discussed. The main issues facing research in regenerative surgery are translation of animal model work into human models, increasing stem cell availability so it can be used to further research, and development of better facilities to enable implementation of these advances.

Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic.

Science.gov (United States)

Whiting, Paul; Kerby, Julie; Coffey, Peter; da Cruz, Lyndon; McKernan, Ruth

2015-10-19

Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic. © 2015 The Author(s).

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

Science.gov (United States)

Finosh, G.T.; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

Emdogain in regenerative periodontal therapy. A review of the literature.

NARCIS (Netherlands)

Sculean, A.; Windisch, P.; Dori, F.; Keglevich, T.; Molnar, B.; Gera, I.

2007-01-01

The goal of regenerative periodontal therapy is the reconstitution of the lost periodontal structures (i.e. the new formation of root cementum, periodontal ligament and alveolar bone). Results from basic research have pointed to the important role of the enamel matrix protein derivative (EMD) in the

Regenerative medicine blueprint.

Science.gov (United States)

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.

Free radical scavenging injectable hydrogels for regenerative therapy.

Science.gov (United States)

Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2017-02-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies

Directory of Open Access Journals (Sweden)

Catherine D. McCusker

2014-06-01

Full Text Available Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this positional information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the positional information in grafted cell populations, and to promote the communication of positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying positional information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.

New tools in regenerative medicine: gene therapy.

Science.gov (United States)

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.

Potential feasibility of dental stem cells for regenerative therapies: stem cell transplantation and whole-tooth engineering.

Science.gov (United States)

Nakahara, Taka

2011-07-01

Multipotent mesenchymal stem cells from bone marrow are expected to be a somatic stem cell source for the development of new cell-based therapy in regenerative medicine. However, dental clinicians are unlikely to carry out autologous cell/tissue collection from patients (i.e., marrow aspiration) as a routine procedure in their clinics; hence, the utilization of bone marrow stem cells seems impractical in the dental field. Dental tissues harvested from extracted human teeth are well known to contain highly proliferative and multipotent stem cell compartments and are considered to be an alternative autologous cell source in cell-based medicine. This article provides a short overview of the ongoing studies for the potential application of dental stem cells and suggests the utilization of 2 concepts in future regenerative medicine: (1) dental stem cell-based therapy for hepatic and other systemic diseases and (2) tooth replacement therapy using the bioengineered human whole tooth, called the "test-tube dental implant." Regenerative therapies will bring new insights and benefits to the fields of clinical medicine and dentistry.

Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

International Nuclear Information System (INIS)

Tsuno, Hiroaki; Yoshida, Toshiko; Nogami, Makiko; Koike, Chika; Okabe, Motonori; Noto, Zenko; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

2012-01-01

Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

The pharmacology of regenerative medicine.

Science.gov (United States)

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.

Regenerative medicine primer.

Science.gov (United States)

Terzic, Andre; Nelson, Timothy J

2013-07-01

The pandemic of chronic diseases, compounded by the scarcity of usable donor organs, mandates radical innovation to address the growing unmet needs of individuals and populations. Beyond life-extending measures that are often the last available option, regenerative strategies offer transformative solutions in treating degenerative conditions. By leveraging newfound knowledge of the intimate processes fundamental to organogenesis and healing, the emerging regenerative armamentarium aims to boost the aptitude of human tissues for self-renewal. Regenerative technologies strive to promote, augment, and reestablish native repair processes, restituting organ structure and function. Multimodal regenerative approaches incorporate transplant of healthy tissues into damaged environments, prompt the body to enact a regenerative response in damaged tissues, and use tissue engineering to manufacture new tissue. Stem cells and their products have a unique aptitude to form specialized tissues and promote repair signaling, providing active ingredients of regenerative regimens. Concomitantly, advances in materials science and biotechnology have unlocked additional prospects for growing tissue grafts and engineering organs. Translation of regenerative principles into practice is feasible and safe in the clinical setting. Regenerative medicine and surgery are, thus, poised to transit from proof-of-principle studies toward clinical validation and, ultimately, standardization, paving the way for next-generation individualized management algorithms. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

Energy Technology Data Exchange (ETDEWEB)

Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

2012-12-01

Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

Regenerative Perspective in Modern Dentistry

Directory of Open Access Journals (Sweden)

Mihnea Ioan Nicolescu

2016-04-01

Full Text Available This review aims to trace the contour lines of regenerative dentistry, to offer an introductory overview on this emerging field to both dental students and practitioners. The crystallized depiction of the concept is a translational approach, connecting dental academics to scientific research and clinical utility. Therefore, this review begins by presenting the general features of regenerative medicine, and then gradually introduces the specific aspects of major dental subdomains, highlighting the progress achieved during the last years by scientific research and, in some cases, which has already been translated into clinical results. The distinct characteristics of stem cells and their microenvironment, together with their diversity in the oral cavity, are put into the context of research and clinical use. Examples of regenerative studies regarding endodontic and periodontal compartments, as well as hard (alveolar bone and soft (salivary glands related tissues, are presented to make the reader further acquainted with the topic. Instead of providing a conclusion, we will emphasize the importance for all dental community members, from young students to experienced dentists, of an early awareness rising regarding biomedical research progress in general and regenerative dentistry in particular.

Turning Regenerative Medicine Breakthrough Ideas and Innovations into Commercial Products.

Science.gov (United States)

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.

Ethical considerations in the translation of regenerative biofabrication technologies into clinic and society.

Science.gov (United States)

Otto, I A; Breugem, C C; Malda, J; Bredenoord, A L

2016-10-07

Biofabrication technologies have the potential to improve healthcare by providing highly advanced and personalized biomedical products for research, treatment and prevention. As the combining of emerging techniques and integrating various biological and synthetic components becomes increasingly complex, it is important that relevant stakeholders anticipate the translation of biofabricated 3D tissue products into patients and society. Ethics is sometimes regarded as a brake on scientific progress, yet from our perspective, ethics in parallel with research anticipates societal impacts of emerging technologies and stimulates responsible innovation. For the ethical assessment, the biofabrication field benefits from similarities to regenerative medicine and an increasing ethical awareness in the development of tissue-engineered products. However, the novelty of the technology itself, the increase in attainable structural complexity, and the potential for automation and personalization are distinguishing facets of biofabrication that call for a specific exploration of the ethics of biofabrication. This review aims to highlight important points of existing ethical discussions, as well as to call attention to emerging issues specific to 3D biofabrication in bench and bedside research and the translation to society.

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

Science.gov (United States)

Finosh, G T; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine.

Science.gov (United States)

Samsonraj, Rebekah M; Raghunath, Michael; Nurcombe, Victor; Hui, James H; van Wijnen, Andre J; Cool, Simon M

2017-12-01

Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Translational research on advanced therapies

Directory of Open Access Journals (Sweden)

Filippo Belardelli

2011-01-01

Full Text Available Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

Translational research on advanced therapies.

Science.gov (United States)

Belardelli, Filippo; Rizza, Paola; Moretti, Franca; Carella, Cintia; Galli, Maria Cristina; Migliaccio, Giovanni

2011-01-01

Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP) are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP) facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues) is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

Translating regenerative medicine techniques for the treatment of epilepsy

Directory of Open Access Journals (Sweden)

Takao Yasuhara

2017-01-01

Full Text Available Epilepsy is considered a chronic neurological disorder and is accompanied by persistent and diverse disturbances in electrical brain activity. While antiepileptic pharmaceuticals are still the predominant treatment for epilepsy, the advent of numerous surgical interventions has further improved outcomes for patients. Despite these advancements, a subpopulation continues to experience intractable seizures which are resistant to current conventional and nonconventional therapeutic options. In this review, we begin with an introduction to the clinical presentation of epilepsy before discussing the clinically relevant laboratory models of epilepsy. Finally, we explore the implications of regenerative medicine – including cell therapy, neuroprotective agents, and electrical stimulation – for epilepsy, supplemented with our laboratory's data. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects.

Science.gov (United States)

Pogozhykh, Olena; Prokopyuk, Volodymyr; Figueiredo, Constança; Pogozhykh, Denys

2018-01-01

Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine.

Engineering growth factors for regenerative medicine applications.

Energy Technology Data Exchange (ETDEWEB)

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.

Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects

Directory of Open Access Journals (Sweden)

Olena Pogozhykh

2018-01-01

Full Text Available Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine.

Translation and adaptation procedures for music therapy outcome instruments

DEFF Research Database (Denmark)

Ridder, Hanne Mette Ochsner; McDermott, Orii; Orrell, Martin

2017-01-01

With increasing occurrence of international multicentre studies, there is a need for music therapy outcome measures to become more widely available across countries. For countries where English is not the first language, translation and cross-cultural adaptation of outcome measures may be necessa...... procedural steps for the translation and adaptation of music therapy outcome instruments. OBS: 50 free online copies to share: http://www.tandfonline.com/eprint/d8TPZbkVMjzgKg7DjcmT/full......With increasing occurrence of international multicentre studies, there is a need for music therapy outcome measures to become more widely available across countries. For countries where English is not the first language, translation and cross-cultural adaptation of outcome measures may be necessary....... A literature review identified a knowledge gap regarding translation procedures of outcome measures used in music therapy research. However, a large body of translation guidelines is available in other health professions. We used the guidelines from these related fields to identify guidelines and outline...

Clinical concepts for regenerative therapy in intrabony defects.

Science.gov (United States)

Cortellini, Pierpaolo; Tonetti, Maurizio S

2015-06-01

Evidence indicates that periodontal regeneration is an efficacious and predictable procedure for the treatment of isolated and multiple intrabony defects. Meta-analyses from systematic reviews indicate an added benefit, in terms of clinical attachment level gain, when demineralized freeze-dried bone allograft, barrier membranes and active biologic products/compounds are applied in addition to open flap debridement. On the other hand, a consistent amount of variability of the outcomes is evident among different studies and within the experimental population of each study. This variability is explained, at least in part, by different patient and defect characteristics. Patient-related factors include smoking habit, compliance with home oral hygiene and residual inflammation after cause-related therapy. Defect-associated factors include defect depth and radiographic angle, the number of residual bony walls, pocket depth and the degree of hypermobility. In addition, surgical-related variables, such as surgical skill, clinical experience and knowledge, and application of the different regenerative materials, have a significant impact on clinical outcomes. This paper presents a strategy to optimize the clinical outcomes of periodontal regeneration. The surgical design of the flap, the use of different regenerative materials and the application of appropriate passive sutures are discussed in this review along with the scientific foundations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recent considerations in regenerative endodontic treatment approaches

Directory of Open Access Journals (Sweden)

Hacer Aksel

2014-09-01

Conclusion: Although the regenerative treatment approaches have good clinical outcomes in the majority of case reports, the outcomes are unpredictable. Since the current clinical protocols for regenerative endodontics do not fully fulfill the triad of tissue engineering ((growth factors, scaffold and stem cells, further translational studies are required to achieve more pulp- and dentin-like tissue in the root canal system to achieve pulp regeneration.

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

Science.gov (United States)

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. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol.

Science.gov (United States)

Suen, Colin M; Zhai, Alex; Lalu, Manoj M; Welsh, Christopher; Levac, Brendan M; Fergusson, Dean; McIntyre, Lauralyn; Stewart, Duncan J

2016-05-25

Pulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies (i.e., therapies involving cells with stem or progenitor-like properties) could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies. We will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and

The application of an enamel matrix protein derivative (Emdogain) in regenerative periodontal therapy: a review.

NARCIS (Netherlands)

Sculean, A.; Schwarz, F.; Becker, J.; Brecx, M.

2007-01-01

Regenerative periodontal therapy aims at reconstitution of the lost periodontal structures such as new formation of root cementum, periodontal ligament and alveolar bone. Findings from basic research indicate that enamel matrix protein derivative (EMD) has a key role in periodontal wound healing.

Researches on regenerative medicine-current state

Directory of Open Access Journals (Sweden)

WANG Zheng-guo

2012-11-01

Full Text Available 【Abstract】 Since 1980s, the rapid development of tissue engineering and stem cell research has pushed re-generative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine. The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine. In accord with this strategy, the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD for the research on regenerative medicine. In order to push the translation of regenerative medicine forward—from bench to bedside, a strategic alliance has been established, and it includes 27 top-level research institutes, medical institutes, colleges, universities and enterprises in the field of stem cell and regeneration medicine. Recently the journal, Science, has published a special issue—Regenerative Medi-cine in China, consisting of 35 papers dealing with stem cell and regeneration, tissue engineering and regeneration, trauma and regeneration and bases for tissue repair and regenerative medicine. It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years. Key words: Regenerative medicine; Tissue engineering; Stem cells; Wound healing

Advances toward regenerative medicine in the central nervous system: challenges in making stem cell therapy a viable clinical strategy.

Science.gov (United States)

Stoll, Elizabeth A

2014-01-01

Over recent years, there has been a great deal of interest in the prospects of stem cell-based therapies for the treatment of nervous system disorders. The eagerness of scientists, clinicians, and spin-out companies to develop new therapies led to premature clinical trials in human patients, and now the initial excitement has largely turned to skepticism. Rather than embracing a defeatist attitude or pressing blindly ahead, I argue it is time to evaluate the challenges encountered by regenerative medicine in the central nervous system and the progress that is being made to solve these problems. In the twenty years since the adult brain was discovered to have an endogenous regenerative capacity, much basic research has been done to elucidate mechanisms controlling proliferation and cellular identity; how stem cells may be directed into neuronal lineages; genetic, pharmacological, and behavioral interventions that modulate neurogenic activity; and the exact nature of limitations to regeneration in the adult, aged, diseased and injured CNS. These findings should prove valuable in designing realistic clinical strategies to improve the prospects of stem cell-based therapies. In this review, I discuss how basic research continues to play a critical role in identifying both barriers and potential routes to regenerative therapy in the CNS.

Part II: Functional delivery of a neurotherapeutic gene to neural stem cells using minicircle DNA and nanoparticles: Translational advantages for regenerative neurology.

Science.gov (United States)

Fernandes, Alinda R; Chari, Divya M

2016-09-28

Both neurotrophin-based therapy and neural stem cell (NSC)-based strategies have progressed to clinical trials for treatment of neurological diseases and injuries. Brain-derived neurotrophic factor (BDNF) in particular can confer neuroprotective and neuro-regenerative effects in preclinical studies, complementing the cell replacement benefits of NSCs. Therefore, combining both approaches by genetically-engineering NSCs to express BDNF is an attractive approach to achieve combinatorial therapy for complex neural injuries. Current genetic engineering approaches almost exclusively employ viral vectors for gene delivery to NSCs though safety and scalability pose major concerns for clinical translation and applicability. Magnetofection, a non-viral gene transfer approach deploying magnetic nanoparticles and DNA with magnetic fields offers a safe alternative but significant improvements are required to enhance its clinical application for delivery of large sized therapeutic plasmids. Here, we demonstrate for the first time the feasibility of using minicircles with magnetofection technology to safely engineer NSCs to overexpress BDNF. Primary mouse NSCs overexpressing BDNF generated increased daughter neuronal cell numbers post-differentiation, with accelerated maturation over a four-week period. Based on our findings we highlight the clinical potential of minicircle/magnetofection technology for therapeutic delivery of key neurotrophic agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Not Missing the Future: A Call to Action for Investigating the Role of Regenerative Medicine Therapies in Pediatric/Adolescent Sports Injuries.

Science.gov (United States)

Best, Thomas M; Caplan, Arnold; Coleman, Michael; Goodrich, Laurie; Hurd, Jason; Kaplan, Lee D; Noonan, Ben; Schoettle, Philip; Scott, Christopher; Stiene, Henry; Huard, Johnny

In August 2016, a group including sport medicine clinicians, researchers, and a bioethicist met in Vail, Colorado to discuss regenerative medicine and its potential role in youth sports injuries. There was consensus that a call to action is urgently needed to understand the current evidence base, the risks and rewards, and future directions of research and clinical practice for regenerative medicine therapies in youth sports. We present here a summary of our meeting, which was supported by the National Youth Sports Health and Safety Institute (NYSHSI), a partnership between the American College of Sports Medicine (ACSM) and Sanford Health. The group's goal is to educate practitioners and the public, and to pioneer a means of accumulating meaningful clinical data on regenerative medicine therapies in pediatric and adolescent athletes.

The contribution of conceptual frameworks to knowledge translation interventions in physical therapy.

Science.gov (United States)

Hudon, Anne; Gervais, Mathieu-Joël; Hunt, Matthew

2015-04-01

There is growing recognition of the importance of knowledge translation activities in physical therapy to ensure that research findings are integrated into clinical practice, and increasing numbers of knowledge translation interventions are being conducted. Although various frameworks have been developed to guide and facilitate the process of translating knowledge into practice, these tools have been infrequently used in physical therapy knowledge translation studies to date. Knowledge translation in physical therapy implicates multiple stakeholders and environments and involves numerous steps. In light of this complexity, the use of explicit conceptual frameworks by clinicians and researchers conducting knowledge translation interventions is associated with a range of potential benefits. This perspective article argues that such frameworks are important resources to promote the uptake of new evidence in physical therapist practice settings. Four key benefits associated with the use of conceptual frameworks in designing and implementing knowledge translation interventions are identified, and limits related to their use are considered. A sample of 5 conceptual frameworks is evaluated, and how they address common barriers to knowledge translation in physical therapy is assessed. The goal of this analysis is to provide guidance to physical therapists seeking to identify a framework to support the design and implementation of a knowledge translation intervention. Finally, the use of a conceptual framework is illustrated through a case example. Increased use of conceptual frameworks can have a positive impact on the field of knowledge translation in physical therapy and support the development and implementation of robust and effective knowledge translation interventions that help span the research-practice gap. © 2015 American Physical Therapy Association.

Platelet-rich fibrin: a boon in regenerative endodontics.

Science.gov (United States)

Rebentish, Priyanka D; Umashetty, Girish; Kaur, Harpreet; Doizode, Trupthi; Kaslekar, Mithun; Chowdhury, Shouvik

2016-12-01

Research into regenerative dentistry has contributed momentum to the field of molecular biology. Periapical surgery aims at removing periapical pathology to achieve complete wound healing and regeneration of bone and periodontal tissue. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. Platelet-rich fibrin (PRF) is a wonderful tissue-engineering product and has recently gained much popularity due its promising results in wound healing bone induction. The features of this product are an attribute of platelets which, after cellular interactions, release growth factors and have shown application in diverse disciplines of dentistry. This paper is intended to shed light onto the various prospects of PRF and to provide clinical insight into regenerative endodontic therapy.

Periodontal Regenerative Therapy in Patient with Chronic Periodontitis and Type 2 Diabetes Mellitus: A Case Report.

Science.gov (United States)

Seshima, Fumi; Nishina, Makiko; Namba, Takashi; Saito, Atsushi

2016-01-01

We report a case of generalized chronic periodontitis and type 2 diabetes mellitus requiring periodontal treatment including regenerative therapy. The patient was a 66-year-old man who presented with the chief complaint of gingival inflammation and mobile teeth in the molar region. He had been being treated for type 2 diabetes mellitus since 1999. His glycated hemoglobin (HbA1c) level was 7.8%. An initial examination revealed sites with a probing depth of ≥7 mm in the molar region, and radiography revealed angular bone defects in this area. Based on a clinical diagnosis of generalized chronic periodontitis, the patient underwent initial periodontal therapy. An improvement was observed in periodontal conditions on reevaluation, and his HbA1c level showed a reduction to 6.9%. Periodontal regenerative therapy with enamel matrix derivative was then performed on #16, 26, and 27. Following another reevaluation, a removable partial denture was fabricated for #47 and the patient placed on supportive periodontal therapy (SPT). To date, periodontal conditions have remained stable and the patient's HbA1c level has increased to 7.5% during SPT. The results show the importance of collaboration between dentist and physician in managing periodontal and diabetic conditions in such patients.

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Science.gov (United States)

Samsonraj, Rebekah M.; Raghunath, Michael; Nurcombe, Victor; Hui, James H.

2017-01-01

Abstract Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self‐renewal and differentiation into tissue‐specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age‐related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone‐forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical‐grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173–2185 PMID:29076267

State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews

NARCIS (Netherlands)

Peruzzi, Mariangela; de Falco, Elena; Abbate, Antonio; Biondi-Zoccai, Giuseppe; Chimenti, Isotta; Lotrionte, Marzia; Benedetto, Umberto; Delewi, Ronak; Marullo, Antonino G. M.; Frati, Giacomo

2015-01-01

To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. After a systematic database search,

Regenerative medicine applications in combat casualty care.

Science.gov (United States)

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.

Regenerative medicine for diabetes: differentiation of human pluripotent stem cells into functional β-cells in vitro and their proposed journey to clinical translation.

Science.gov (United States)

Bose, Bipasha; Katikireddy, Kishore Reddy; Shenoy, P Sudheer

2014-01-01

Diabetes is a group of metabolic diseases, rising globally at an alarming rate. Type 1 (juvenile diabetes) is the autoimmune version of diabetes where the pancreas is unable to produce insulin, whereas type 2 (adult onset diabetes) is caused due to insulin resistance of the cells. In either of the cases, elevated blood glucose levels are observed which leads to progressive comorbidity like renal failure, cardiovascular disease, retinopathy, etc. Metformin, sulphonyl urea group of drugs, as well as insulin injections are the available therapies. In advanced cases of diabetes, the drug alone or drug in combination with insulin injections are not able to maintain a steady level of blood glucose. Moreover, frequent insulin injections are rather cumbersome for the patient. So, regenerative medicine could be a permanent solution for fighting diabetes. Islet transplantation has been tried with a limited amount of success on a large population of diabetics because of the shortage of cadaveric pancreas. Therefore, the best proposed alternative is regenerative medicine involving human pluripotent stem cell (hPSC)-derived beta islet transplantation which can be obtained in large quantities. Efficient protocols for in vitro differentiation of hPSC into a large number of sustained insulin-producing beta cells for transplantation will be considered to be a giant leap to address global rise in diabetic cases. Although most of the protocols mimic in vivo pancreatic development in humans, considerable amount of lacuna persists for near-perfect differentiation strategies. Moreover, beta islets differentiated from hPSC have not yet been successfully translated under clinical scenario. © 2014 Elsevier Inc. All rights reserved.

Overcoming immunological barriers in regenerative medicine.

Science.gov (United States)

Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

2014-08-01

Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists.

The Contribution of Conceptual Frameworks to Knowledge Translation Interventions in Physical Therapy

Science.gov (United States)

Gervais, Mathieu-Joël; Hunt, Matthew

2015-01-01

There is growing recognition of the importance of knowledge translation activities in physical therapy to ensure that research findings are integrated into clinical practice, and increasing numbers of knowledge translation interventions are being conducted. Although various frameworks have been developed to guide and facilitate the process of translating knowledge into practice, these tools have been infrequently used in physical therapy knowledge translation studies to date. Knowledge translation in physical therapy implicates multiple stakeholders and environments and involves numerous steps. In light of this complexity, the use of explicit conceptual frameworks by clinicians and researchers conducting knowledge translation interventions is associated with a range of potential benefits. This perspective article argues that such frameworks are important resources to promote the uptake of new evidence in physical therapist practice settings. Four key benefits associated with the use of conceptual frameworks in designing and implementing knowledge translation interventions are identified, and limits related to their use are considered. A sample of 5 conceptual frameworks is evaluated, and how they address common barriers to knowledge translation in physical therapy is assessed. The goal of this analysis is to provide guidance to physical therapists seeking to identify a framework to support the design and implementation of a knowledge translation intervention. Finally, the use of a conceptual framework is illustrated through a case example. Increased use of conceptual frameworks can have a positive impact on the field of knowledge translation in physical therapy and support the development and implementation of robust and effective knowledge translation interventions that help span the research-practice gap. PMID:25060959

Advances in individualized and regenerative medicine.

Science.gov (United States)

Blum, Hubert E

2014-03-01

Molecular and cell biology have resulted in major advances in our understanding of disease pathogenesis as well as in novel strategies for the diagnosis, therapy and prevention of human diseases. Based on modern molecular, genetic and biochemical methodologies it is on the one hand possible to identify for example disease-related point mutations and single nucleotide polymorphisms. On the other hand, using high throughput array and other technologies, it is for example possible to simultaneously analyze thousands of genes or gene products (RNA and proteins), resulting in an individual gene or gene expression profile ('signature'). Such data increasingly allow to define the individual disposition for a given disease and to predict disease prognosis as well as the efficacy of therapeutic strategies in the individual patient ('individualized medicine'). At the same time, the basic discoveries in cell biology, including embryonic and adult stem cells, induced pluripotent stem cells, genetically modified cells and others, have moved regenerative medicine into the center of biomedical research worldwide with a major translational impact on tissue engineering as well as transplantation medicine. All these aspects have greatly contributed to the recent advances in regenerative medicine and the development novel concepts for the treatment of many human diseases, including liver diseases. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Application of stem cell/growth factor system, as a multimodal therapy approach in regenerative medicine to improve cell therapy yields.

Science.gov (United States)

Pourrajab, Fatemeh; Babaei Zarch, Mojtaba; Baghi Yazdi, Mohammad; Rahimi Zarchi, Abolfazl; Vakili Zarch, Abbas

2014-04-15

Stem cells hold a great promise for regenerative medicine, especially for replacing cells in infarcted organ that hardly have any intrinsic renewal capacity, including heart and brain. Signaling pathways that regulate pluripotency or lineage-specific gene and protein expression have been the major focus of stem cell research. Between them, there are some well known signaling pathways such as GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines may regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes or accentuate synergistic compliance. For example, contributing factors in the progression of heart failure are both the loss of cardiomyocytes after myocardial infarction, and the absence of an adequate endogenous repair signaling. Combining cell engraftment with therapeutic signaling factor delivery is more exciting in terms of host progenitor/donor stem cell survival and proliferation. Thus stem cell-based therapy, besides triggering signaling pathways through GF/GFR systems can become a realistic option in regenerative processes for replacing lost cells and reconstituting the damaged organ, as before. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Researches on regenerative medicine-current state and prospect.

Science.gov (United States)

Wang, Zheng-Guo; Xiao, Kai

2012-01-01

Since 1980s, the rapid development of tissue engineering and stem cell research has pushed regenerative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine. The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine. In accord with this strategy, the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD) for the research on regenerative medicine. In order to push the translation of regenerative medicine forward-from bench to bedside, a strategic alliance has been established, and it includes 27 top-level research institutes, medical institutes, colleges, universities and enterprises in the field of stem cell and regeneration medicine. Recently the journal, Science, has published a special issue-Regenerative Medicine in China, consisting of 35 papers dealing with stem cell and regeneration, tissue engineering and regeneration, trauma and regeneration and bases for tissue repair and regenerative medicine. It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years).

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions.

Science.gov (United States)

Whitlow, Jonathan; Pacelli, Settimio; Paul, Arghya

2017-09-10

With recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable features have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made toward the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

MicroRNA delivery for regenerative medicine.

Science.gov (United States)

Peng, Bo; Chen, Yongming; Leong, Kam W

2015-07-01

MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages and disadvantages. A number of studies have demonstrated success in augmenting osteogenesis, improving cardiogenesis, and reducing fibrosis among many other tissue engineering applications. A scaffold-based approach with the possibility of local and sustained delivery of miRNA is particularly attractive since the physical cues provided by the scaffold may synergize with the biochemical cues induced by miRNA therapy. Herein, we first briefly cover the application of miRNA to direct stem cell fate via replacement and inhibition therapies, followed by the discussion of the promising viral and nonviral delivery systems. Next we present the unique advantages of a scaffold-based delivery in achieving lineage-specific differentiation and tissue development. Copyright © 2015 Elsevier B.V. All rights reserved.

The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine

International Nuclear Information System (INIS)

Anders, Juanita; Moges, Helina; Wu, Xingjia; Ilev, Ilko; Waynant, Ronald; Longo, Leonardo

2010-01-01

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.

Regenerative medicine: A ray of light for medical science

Directory of Open Access Journals (Sweden)

Swapna Supekar

2016-01-01

Full Text Available The perimeters of medical science have expanded to include regenerative medicine as a translational science, which has the potential to revolutionize the treatment of incapacitating diseases and chronic disorders.

Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

Directory of Open Access Journals (Sweden)

LM Benneker

2014-05-01

Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

Cell-based therapy technology classifications and translational challenges

Science.gov (United States)

Mount, Natalie M.; Ward, Stephen J.; Kefalas, Panos; Hyllner, Johan

2015-01-01

Cell therapies offer the promise of treating and altering the course of diseases which cannot be addressed adequately by existing pharmaceuticals. Cell therapies are a diverse group across cell types and therapeutic indications and have been an active area of research for many years but are now strongly emerging through translation and towards successful commercial development and patient access. In this article, we present a description of a classification of cell therapies on the basis of their underlying technologies rather than the more commonly used classification by cell type because the regulatory path and manufacturing solutions are often similar within a technology area due to the nature of the methods used. We analyse the progress of new cell therapies towards clinical translation, examine how they are addressing the clinical, regulatory, manufacturing and reimbursement requirements, describe some of the remaining challenges and provide perspectives on how the field may progress for the future. PMID:26416686

The 'sweet' spot of cellular pluripotency: protein glycosylation in human pluripotent stem cells and its applications in regenerative medicine.

Science.gov (United States)

Wang, Yu-Chieh; Lin, Victor; Loring, Jeanne F; Peterson, Suzanne E

2015-05-01

Human pluripotent stem cells (hPSCs) promise for the future of regenerative medicine. The structural and biochemical diversity associated with glycans makes them a unique type of macromolecule modification that is involved in the regulation of a vast array of biochemical events and cellular activities including pluripotency in hPSCs. The primary focus of this review article is to highlight recent advances in stem cell research from a glycobiological perspective. We also discuss how our understanding of glycans and glycosylation may help overcome barriers hindering the clinical application of hPSC-derived cells. A literature survey using NCBI-PubMed and Google Scholar was performed in 2014. Regenerative medicine hopes to provide novel strategies to combat human disease and tissue injury that currently lack effective therapies. Although progress in this field is accelerating, many critical issues remain to be addressed in order for cell-based therapy to become a practical and safe treatment option. Emerging evidence suggests that protein glycosylation may significantly influence the regulation of cellular pluripotency, and that the exploitation of protein glycosylation in hPSCs and their differentiated derivatives may lead to transformative and translational discoveries for regenerative medicine. In addition, hPSCs represent a novel research platform for investigating glycosylation-related disease.

The past, present and future of ligament regenerative engineering.

Science.gov (United States)

Mengsteab, Paulos Y; Nair, Lakshmi S; Laurencin, Cato T

2016-12-01

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes.

Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

Directory of Open Access Journals (Sweden)

Tom J. Burdon

2011-01-01

Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

Proceedings of the signature series event of the international society for cellular therapy: "Advancements in cellular therapies and regenerative medicine in digestive diseases," London, United Kingdom, May 3, 2017.

Science.gov (United States)

Ciccocioppo, Rachele; Dos Santos, Claudia C; Baumgart, Daniel C; Cangemi, Giuseppina C; Cardinale, Vincenzo; Ciacci, Carolina; De Coppi, Paolo; Haldar, Debashis; Klersy, Catherine; Nostro, M Cristina; Ott, Michael; Piemonti, Lorenzo; Tomei, Alice A; Uygun, Basak; Vetrano, Stefania; Orlando, Giuseppe

2018-03-01

A summary of the First Signature Series Event, "Advancements in Cellular Therapies and Regenerative Medicine for Digestive Diseases," held on May 3, 2017, in London, United Kingdom, is presented. Twelve speakers from three continents covered major topics in the areas of cellular therapy and regenerative medicine applied to liver and gastrointestinal medicine as well as to diabetes mellitus. Highlights from their presentations, together with an overview of the global impact of digestive diseases and a proposal for a shared online collection and data-monitoring platform tool, are included in this proceedings. Although growing evidence demonstrate the feasibility and safety of exploiting cell-based technologies for the treatment of digestive diseases, regulatory and methodological obstacles will need to be overcome before the successful implementation in the clinic of these novel attractive therapeutic strategies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Advancing pig cloning technologies towards application in regenerative medicine.

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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.

Gingival cyst of the adult: regenerative therapy of associated root exposure. A case report and literature review.

Science.gov (United States)

Kelsey, W Patrick; Kalmar, John R; Tatakis, Dimitris N

2009-12-01

The gingival cyst of the adult (GCA) is an uncommon developmental cyst of odontogenic origin most frequently seen near mandibular canines and premolars and is routinely treated with excisional biopsy. This article presents a case of a GCA treated with a combined regenerative approach and reviews the GCA literature with an emphasis on the clinical aspects of this lesion. A 54 year-old man presented for treatment of generalized severe chronic periodontitis. Clinical examination revealed a cystic lesion in the gingiva of the mandibular canine-premolar area. Radiographs revealed a well-defined radiolucency in the coronal one-third of the tooth roots. Surgical enucleation of the lesion revealed root exposure of the second premolar. Because of the anatomy of the lesion-associated defect, regenerative treatment, using a combination of freeze-dried bone allograft and a collagen membrane, was considered the therapeutic approach of choice. The biopsy revealed histologic features consistent with a GCA. Clinical and radiographic examinations 1 year post-surgery indicated uneventful soft tissue healing and bone fill of the initial defect. The review of the literature revealed only one other case of root exposure associated with GCA and no previous report of regenerative therapy. In rare instances, a GCA lesion may result in tooth-root exposure. In such cases, a combined regenerative treatment approach may be used to achieve resolution.

The future of replacement and restorative therapies: from organ transplantation to regenerative medicine.

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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. Copyright © 2013 Elsevier Inc. All rights reserved.

Translational approach for gene therapy in epilepsy

DEFF Research Database (Denmark)

Ledri, Litsa Nikitidou; Melin, Esbjörn; Christiansen, Søren H.

2016-01-01

clinical trial for gene therapy of temporal lobe epilepsy was explored: We investigated (i) whether the post intrahippocampal kainate-induced status epilepticus (SE) model of chronic epilepsy in rats could be clinically relevant; and (ii) whether a translationally designed neuropeptide Y (NPY)/Y2 receptor...

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

Science.gov (United States)

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. © 2014 EVJ Ltd.

Repairing quite swimmingly: advances in regenerative medicine using zebrafish.

Science.gov (United States)

Goessling, Wolfram; North, Trista E

2014-07-01

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. © 2014. Published by The Company of Biologists Ltd.

Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

Science.gov (United States)

Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

2018-02-27

Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

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

Directory of Open Access Journals (Sweden)

Kátia Maria Sampaio Gomes

Full Text Available Summary 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.

Stem cell hype: media portrayal of therapy translation.

Science.gov (United States)

Kamenova, Kalina; Caulfield, Timothy

2015-03-11

In this Perspective, we examine the portrayal of translational stem cell research in major daily newspapers in Canada, the United States, and the United Kingdom between 2010 and 2013, focusing on how timelines for stem cell therapies were represented before and after Geron terminated its pioneering stem cell program. Our content analysis reveals that press coverage has shifted from ethical, legal, and social issues to clinical translation issues, and highly optimistic timelines were provided with no substantial change in representation over time. Scientists were the dominant voice with respect to translation timelines. The findings raise questions about the degree to which the media's overly optimistic slant fosters unrealistic expectations regarding the speed of clinical translation and highlight the ethical responsibility of stem cell researchers as public communicators. Copyright © 2015, American Association for the Advancement of Science.

Different strategies to improve the use of the umbilical cord and cord blood for hematopoietic and other regenerative cell therapies

NARCIS (Netherlands)

Garde, Mark Paul van der

2016-01-01

The umbilical cord and cord blood contain stem cells that can be used for regenerative cell therapies such as hematopoietic stem cell transplantation. However, the application of cord blood is hindered by the slow engraftment of the cells and delayed immune reconstitution compared to stem cells of

Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke.

Science.gov (United States)

Peña, Ike dela; Borlongan, Cesar V

2015-12-01

Among recently investigated stroke therapies, stem cell treatment holds great promise by virtue of their putative ability to replace lost cells, promote endogenous neurogenesis,and produce behavioral and functional improvement through their "bystander effects." Translating stem cell in the clinic, however, presents a number of technical difficulties. A strategy suggested to enhance therapeutic utility of stem cells is combination therapy, i.e., co-transplantation of stem cells or adjunct treatment with pharmacological agents and substrates,which is assumed to produce more profound therapeutic benefits by circumventing limitations of individual treatments and facilitating complementary brain repair processes. We previously demonstrated enhanced functional effects of cotreatment with granulocyte-colony stimulating factor (GCSF)and human umbilical cord blood cell (hUCB) transplantation in animal models of traumatic brain injury (TBI). Here,we suggest that the aforementioned combination therapy may also produce synergistic effects in stroke. Accordingly, G-CSF treatment may reduce expression of pro-inflammatory cytokines and enhance neurogenesis rendering a receptive microenvironment for hUCB engraftment. Adjunct treatment of GCSF with hUCB may facilitate stemness maintenance and guide neural lineage commitment of hUCB cells. Moreover, regenerative mechanisms afforded by G-CSF-mobilized endogenous stem cells, secretion of growth factors by hUCB grafts and G-CSF-recruited endothelial progenitor cells(EPCs), as well as the potential graft–host integration that may promote synaptic circuitry re-establishment could altogether produce more pronounced functional improvement in stroked rats subjected to a combination G-CSF treatment and hUCB transplantation. Nevertheless, differences in pathology and repair processes underlying TBI and stroke deserve consideration when testing the effects of combinatorial G-CSF and hUCB cell transplantation for stroke treatment. Further

Innovative regenerative medicines in the EU: a better future in evidence?

Science.gov (United States)

Corbett, Mark S; Webster, Andrew; Hawkins, Robert; Woolacott, Nerys

2017-03-08

Despite a steady stream of headlines suggesting they will transform the future of healthcare, high-tech regenerative medicines have, to date, been quite inaccessible to patients, with only eight having been granted an EU marketing licence in the last 7 years. Here, we outline some of the historical reasons for this paucity of licensed innovative regenerative medicines. We discuss the challenges to be overcome to expedite the development of this complex and rapidly changing area of medicine, together with possible reasons to be more optimistic for the future. Several factors have contributed to the scarcity of cutting-edge regenerative medicines in clinical practice. These include the great expense and difficulties involved in planning how individual therapies will be developed, manufactured to commercial levels and ultimately successfully delivered to patients. Specific challenges also exist when evaluating the safety, efficacy and cost-effectiveness of these therapies. Furthermore, many treatments are used without a licence from the European Medicines Agency, under "Hospital Exemption" from the EC legislation. For products which are licensed, alternative financing approaches by healthcare providers may be needed, since many therapies will have significant up-front costs but uncertain benefits and harms in the long-term. However, increasing political interest and more flexible mechanisms for licensing and financing of therapies are now evident; these could be key to the future growth and development of regenerative medicine in clinical practice. Recent developments in regulatory processes, coupled with increasing political interest, may offer some hope for improvements to the long and often difficult routes from laboratory to marketplace for leading-edge cell or tissue therapies. Collaboration between publicly-funded researchers and the pharmaceutical industry could be key to the future development of regenerative medicine in clinical practice; such collaborations

Translational and Regulatory Challenges for Exon Skipping Therapies

NARCIS (Netherlands)

Aartsma-Rus, Annemieke; Ferlini, Alessandra; Goemans, Nathalie; Pasmooij, Anna M. G.; Wells, Dominic J.; Bushby, Katerine; Vroom, Elizabeth; Balabanov, Pavel

2014-01-01

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and

Hierarchical Design of Tissue Regenerative Constructs.

Science.gov (United States)

Rose, Jonas C; De Laporte, Laura

2018-03-01

The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell-induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer-scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native-like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances in regenerative therapies for spinal cord injury: a biomaterials approach

Directory of Open Access Journals (Sweden)

Magdalini Tsintou

2015-01-01

Full Text Available Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mechanism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing research interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaffold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerative/neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction.

Essentials of 3D biofabrication and translation

CERN Document Server

Atala, Anthony

2015-01-01

Essentials of 3D Biofabrication and Translation discusses the techniques that are making bioprinting a viable alternative in regenerative medicine. The book runs the gamut of topics related to the subject, including hydrogels and polymers, nanotechnology, toxicity testing, and drug screening platforms, also introducing current applications in the cardiac, skeletal, and nervous systems, and organ construction. Leaders in clinical medicine and translational science provide a global perspective of the transformative nature of this field, including the use of cells, biomaterials, and macromolecules to create basic building blocks of tissues and organs, all of which are driving the field of biofabrication to transform regenerative medicine. Provides a new and versatile method to fabricating living tissue Discusses future applications for 3D bioprinting technologies, including use in the cardiac, skeletal, and nervous systems, and organ construction Describes current approaches and future challenges for translation...

Conference Report: 6th Annual International Symposium on Regenerative Rehabilitation.

Science.gov (United States)

Loghmani, M Terry; Roche, Joseph A

2018-04-03

The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR 3 T), included a preconference meeting of institutional representatives of the International Consortium of Regenerative Rehabilitation, keynote talks from distinguished scientists, platform and poster presentations from experts and trainees, panel discussions and postconference workshops. The following priorities were identified: increasing rigor in basic, preclinical and clinical studies, especially the use of better controls; developing better outcome measures for preclinical and clinical trials; focusing on developing more tissue-based interventions versus cell-based interventions; including regenerative rehabilitation in curricula of professional programs like occupational and physical therapy; and developing better instruments to quantify rehabilitative interventions.

Regenerative Medicine: Advances from Developmental to Degenerative Diseases.

Science.gov (United States)

Blair, Nicholas F; Frith, Thomas J R; Barbaric, Ivana

2017-01-01

Chronic tissue and organ failure caused by an injury, disease, ageing or congenital defects represents some of the most complex therapeutic challenges and poses a significant financial healthcare burden. Regenerative medicine strategies aim to fulfil the unmet clinical need by restoring the normal tissue function either through stimulating the endogenous tissue repair or by using transplantation strategies to replace the missing or defective cells. Stem cells represent an essential pillar of regenerative medicine efforts as they provide a source of progenitors or differentiated cells for use in cell replacement therapies. Whilst significant leaps have been made in controlling the stem cell fates and differentiating them to cell types of interest, transitioning bespoke cellular products from an academic environment to off-the-shelf clinical treatments brings about a whole new set of challenges which encompass manufacturing, regulatory and funding issues. Notwithstanding the need to resolve such issues before cell replacement therapies can benefit global healthcare, mounting progress in the field has highlighted regenerative medicine as a realistic prospect for treating some of the previously incurable conditions.

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

Science.gov (United States)

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.

Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

Science.gov (United States)

Sanchez-Martin, Manuel

2008-09-01

The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

MicroRNA Delivery for Regenerative Medicine

OpenAIRE

Peng, Bo; Chen, Yongming; Leong, Kam W.

2015-01-01

MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages an...

Regenerative endodontics: a comprehensive review.

Science.gov (United States)

Kim, S G; Malek, M; Sigurdsson, A; Lin, L M; Kahler, B

2018-05-19

The European Society of Endodontology and the American Association for Endodontists have released position statements and clinical considerations for regenerative endodontics. There is increasing literature on this field since the initial reports of Iwaya et al. (Dental Traumatology, 17, 2001, 185) and Banchs & Trope (Journal of Endodontics, 30, 2004, 196). Endogenous stem cells from an induced periapical bleeding and scaffolds using blood clot, platelet rich plasma or platelet-rich fibrin have been utilized in regenerative endodontics. This approach has been described as a 'paradigm shift' and considered the first treatment option for immature teeth with pulp necrosis. There are three treatment outcomes of regenerative endodontics; (i) resolution of clinical signs and symptoms; (ii) further root maturation; and (iii) return of neurogenesis. It is known that results are variable for these objectives, and true regeneration of the pulp/dentine complex is not achieved. Repair derived primarily from the periodontal and osseous tissues has been shown histologically. It is hoped that with the concept of tissue engineering, namely stem cells, scaffolds and signalling molecules, that true pulp regeneration is an achievable goal. This review discusses current knowledge as well as future directions for regenerative endodontics. Patient-centred outcomes such as tooth discolouration and possibly more appointments with the potential for adverse effects needs to be discussed with patients and parents. Based on the classification of Cvek (Endodontics and Dental Traumatology, 8, 1992, 45), it is proposed that regenerative endodontics should be considered for teeth with incomplete root formation although teeth with near or complete root formation may be more suited for conventional endodontic therapy or MTA barrier techniques. However, much is still not known about clinical and biological aspects of regenerative endodontics. © 2018 International Endodontic Journal. Published by

Translational Applications of Molecular Imaging and Radionuclide Therapy

International Nuclear Information System (INIS)

Welch, Michael J.; Eckelman, William C.; Vera, David

2005-01-01

Molecular imaging is becoming a larger part of imaging research and practice. The Office of Biological and Environmental Research of the Department of Energy funds a significant number of researchers in this area. The proposal is to partially fund a workshop to inform scientists working in nuclear medicine and nuclear medicine practitioners of the recent advances of molecular imaging in nuclear medicine as well as other imaging modalities. A limited number of topics related to radionuclide therapy will also be discussed. The proposal is to request partial funds for the workshop entitled ''Translational Applications of Molecular Imaging and Radionuclide Therapy'' to be held prior to the Society of Nuclear Medicine Annual Meeting in Toronto, Canada in June 2005. The meeting will be held on June 17-18. This will allow scientists interested in all aspects of nuclear medicine imaging to attend. The chair of the organizing group is Dr. Michael J. Welch. The organizing committee consists of Dr. Welch, Dr. William C. Eckelman and Dr. David Vera. The goal is to invite speakers to discuss the most recent advances of modern molecular imaging and therapy. Speakers will present advances made in in vivo tagging imaging assays, technical aspects of small animal imaging, in vivo imaging and bench to bedside translational study; and the role of a diagnostic scan on therapy selection. This latter topic will include discussions on therapy and new approaches to dosimetry. Several of these topics are those funded by the Department of Energy Office of Biological and Environmental Research

Advances in stem cells and regenerative medicine: single-cell dynamics, new models and translational perspectives.

Science.gov (United States)

Twigger, Alecia-Jane; Scheel, Christina H

2017-09-01

An international cohort of over 300 stem cell biologists came together in Heidelberg, Germany in May 2017 as delegates of the 'Advances in Stem Cells and Regenerative Medicine' conference run through the European Molecular Biology Organization. This Meeting Review highlights the novel insights into stem cell regulation, new technologies aiding in discovery and exciting breakthroughs in the field of regenerative medicine that emerged from the meeting. © 2017. Published by The Company of Biologists Ltd.

Liver regenerative medicine: advances and challenges.

Science.gov (United States)

Chistiakov, Dimitry A

2012-01-01

Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.

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Kadyk, Lisa C; DeWitt, Natalie D; Gomperts, Brigitte

2017-10-01

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease.

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Gan, Earn H; Pearce, Simon H

2017-03-01

The treatment for autoimmune Addison's disease (AAD) has remained virtually unchanged in the last 60 years. Most patients have symptoms that are relatively well controlled with exogenous steroid replacement, but there may be persistent symptoms, recurrent adrenal crisis and poor quality of life, despite good compliance with optimal current treatments. Treatment with conventional exogenous steroid therapy is also associated with premature mortality, increased cardiovascular risk and complications related to excessive steroid replacement. Hence, novel therapeutic approaches have emerged in the last decade attempting to improve the long-term outcome and quality of life of patients with AAD. This review discusses the recent developments in treatment innovations for AAD, including the novel exogenous steroid formulations with the intention of mimicking the physiological biorhythm of cortisol secretion. Our group has also carried out a few studies attempting to restore endogenous glucocorticoid production via immunomodulatory and regenerative medicine approaches. The recent advances in the understanding of adrenocortical stem cell biology, and adrenal plasticity will also be discussed to help comprehend the science behind the therapeutic approaches adopted. © 2017 European Society of Endocrinology.

Transplantation of umbilical cord blood-derived cells for novel indications in regenerative therapy or immune modulation: a scoping review of clinical studies.

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Iafolla, Marco A J; Tay, Jason; Allan, David S

2014-01-01

Although used mainly for transplantation of hematopoietic stem cells in the treatment of blood disorders, umbilical cord blood (UCB)-based therapies are now being used increasingly for novel applications in nonhematopoietic diseases and as a form of cellular regenerative therapy or immune modulation. We performed a systematic scoping review by searching Medline, EMBASE, and the Cochrane Library for published articles, and we searched www.clinicaltrials.com and the World Health Organization International Clinical Trials Registry Platform to describe the breadth of published studies and ongoing clinical activity in umbilical cord-based cellular therapy for regenerative therapy and immune modulation. The most commonly published area of expertise in the use of UCB-derived cellular transplantation for novel indications is for neurological disorders and this remains the most active area of study in ongoing registered trials. An increasingly broad range of disorders, however, are reflected in ongoing registered trials, which suggests greater activity, interest, and investment in UCB-derived cellular therapy. Interestingly, adult patients compose the majority of patients reported in published reports and registered ongoing clinical studies continue to enroll predominantly adult subjects. Geographically, Asian countries appear most active in UCB-derived cellular therapy and our analysis of ongoing studies suggests this trend will likely continue. Regular assessment of published and ongoing activity in UCB transplantation for emerging novel indications will be critical for informing UCB banking establishments and funding agencies to guide changes in banking practices related to emerging trends in cell therapy. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Regenerative Endodontics: A Road Less Travelled

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Bansal, Ramta; Mittal, Sunandan; Kumar, Tarun; Kaur, Dilpreet

2014-01-01

Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering. PMID:25478476

Concise Review: Microfluidic Technology Platforms: Poised to Accelerate Development and Translation of Stem Cell-Derived Therapies

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Titmarsh, Drew M.; Chen, Huaying; Glass, Nick R.; Cooper-White, Justin J.

2014-01-01

Stem cells are a powerful resource for producing a variety of cell types with utility in clinically associated applications, including preclinical drug screening and development, disease and developmental modeling, and regenerative medicine. Regardless of the type of stem cell, substantial barriers to clinical translation still exist and must be overcome to realize full clinical potential. These barriers span processes including cell isolation, expansion, and differentiation; purification, quality control, and therapeutic efficacy and safety; and the economic viability of bioprocesses for production of functional cell products. Microfluidic systems have been developed for a myriad of biological applications and have the intrinsic capability of controlling and interrogating the cellular microenvironment with unrivalled precision; therefore, they have particular relevance to overcoming such barriers to translation. Development of microfluidic technologies increasingly utilizes stem cells, addresses stem cell-relevant biological phenomena, and aligns capabilities with translational challenges and goals. In this concise review, we describe how microfluidic technologies can contribute to the translation of stem cell research outcomes, and we provide an update on innovative research efforts in this area. This timely convergence of stem cell translational challenges and microfluidic capabilities means that there is now an opportunity for both disciplines to benefit from increased interaction. PMID:24311699

A survey of attitude and opinions of endodontic residents towards regenerative endodontics

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Utneja, Shivani; Nawal, Ruchika Roongta; Ansari, Mohammed Irfan; Talwar, Sangeeta; Verma, Mahesh

2013-01-01

Aim: The objective of this survey was to study the level of awareness, current state of knowledge and opinions towards regenerative endodontic treatments amongst the endodontic residents of India. Settings and Design: Questionnaire based survey was designed. Materials and Methods: After approval from the organizing committee of 26th Federation of Operative Dentistry of India and 19th Indian Endodontic Society National conference 2011, 200 copies of the questionnaire were circulated amongst the endodontic residents in conservative dentistry and endodontics at various colleges across the country about regenerative endodontic procedures. The survey included profile of the respondents and consisted of 23 questions about their knowledge, attitude and opinions regarding use of these procedures as part of future dental treatment. Results: The survey showed that half the participants (50.6%) had received continued education in stem cells and/or regenerative dental treatments. The majority of participants were of the opinion (86.6%) that regenerative therapy should be incorporated into dentistry, and most of them (88%) were willing to acquire training in learning this new treatment strategy. The results indicated that half of the participants (52.6%) were already using some type of regenerative therapy in their clinical practice; however, with a majority of these limited to use of membranes, scaffolds or bioactive materials. Conclusions: These results reflect that endodontic residents are optimistic about the use of regenerative endodontic procedures; however, a need for more research and training was felt. PMID:23956532

Regenerative medicine: looking backward 10 years further on.

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Kemp, Paul

2016-12-01

The last decade has seen considerable changes in the Regenerative Medicine industry, but unfortunately the hope for numerous treatments that 'replace or regenerate human cells, tissues or organs to restore or establish normal function' has not yet emerged. In contrast to this, there have been major advances in the field of cellular immunotherapy though some do not consider these to be Regenerative Medicines. Regulatory changes have in some cases improved the route to a marketing license but they have not been matched by clarification of the complex, national reimbursement processes for cell-based treatments and this has adversely affected a number of leading Regenerative Medicine Companies. The review considers the direction that the industry may go in the future in relation to scientific, manufacturing and clinical strategies which may improve the rate of success of new therapies..

Regeneration and Repair in Endodontics—A Special Issue of the Regenerative Endodontics—A New Era in Clinical Endodontics

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Saoud, Tarek Mohamed A.; Ricucci, Domenico; Lin, Louis M.; Gaengler, Peter

2016-01-01

Caries is the most common cause of pulp-periapical disease. When the pulp tissue involved in caries becomes irreversibly inflamed and progresses to necrosis, the treatment option is root canal therapy because the infected or non-infected necrotic pulp tissue in the root canal system is not accessible to the host's innate and adaptive immune defense mechanisms and antimicrobial agents. Therefore, the infected or non-infected necrotic pulp tissue must be removed from the canal space by pulpectomy. As our knowledge in pulp biology advances, the concept of treatment of pulpal and periapical disease also changes. Endodontists have been looking for biologically based treatment procedures, which could promote regeneration or repair of the dentin-pulp complex destroyed by infection or trauma for several decades. After a long, extensive search in in vitro laboratory and in vivo preclinical animal experiments, the dental stem cells capable of regenerating the dentin-pulp complex were discovered. Consequently, the biological concept of ‘regenerative endodontics’ emerged and has highlighted the paradigm shift in the treatment of immature permanent teeth with necrotic pulps in clinical endodontics. Regenerative endodontics is defined as biologically based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as the pulp-dentin complex. According to the American Association of Endodontists’ Clinical Considerations for a Regenerative Procedure, the primary goal of the regenerative procedure is the elimination of clinical symptoms and the resolution of apical periodontitis. Thickening of canal walls and continued root maturation is the secondary goal. Therefore, the primary goal of regenerative endodontics and traditional non-surgical root canal therapy is the same. The difference between non-surgical root canal therapy and regenerative endodontic therapy is that the disinfected root canals in the former

Regeneration and Repair in Endodontics-A Special Issue of the Regenerative Endodontics-A New Era in Clinical Endodontics.

Science.gov (United States)

Saoud, Tarek Mohamed A; Ricucci, Domenico; Lin, Louis M; Gaengler, Peter

2016-02-27

Caries is the most common cause of pulp-periapical disease. When the pulp tissue involved in caries becomes irreversibly inflamed and progresses to necrosis, the treatment option is root canal therapy because the infected or non-infected necrotic pulp tissue in the root canal system is not accessible to the host's innate and adaptive immune defense mechanisms and antimicrobial agents. Therefore, the infected or non-infected necrotic pulp tissue must be removed from the canal space by pulpectomy. As our knowledge in pulp biology advances, the concept of treatment of pulpal and periapical disease also changes. Endodontists have been looking for biologically based treatment procedures, which could promote regeneration or repair of the dentin-pulp complex destroyed by infection or trauma for several decades. After a long, extensive search in in vitro laboratory and in vivo preclinical animal experiments, the dental stem cells capable of regenerating the dentin-pulp complex were discovered. Consequently, the biological concept of 'regenerative endodontics' emerged and has highlighted the paradigm shift in the treatment of immature permanent teeth with necrotic pulps in clinical endodontics. Regenerative endodontics is defined as biologically based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as the pulp-dentin complex. According to the American Association of Endodontists' Clinical Considerations for a Regenerative Procedure, the primary goal of the regenerative procedure is the elimination of clinical symptoms and the resolution of apical periodontitis. Thickening of canal walls and continued root maturation is the secondary goal. Therefore, the primary goal of regenerative endodontics and traditional non-surgical root canal therapy is the same. The difference between non-surgical root canal therapy and regenerative endodontic therapy is that the disinfected root canals in the former therapy are

Regeneration and Repair in Endodontics—A Special Issue of the Regenerative Endodontics—A New Era in Clinical Endodontics

Directory of Open Access Journals (Sweden)

Tarek Mohamed A. Saoud

2016-02-01

Full Text Available Caries is the most common cause of pulp-periapical disease. When the pulp tissue involved in caries becomes irreversibly inflamed and progresses to necrosis, the treatment option is root canal therapy because the infected or non-infected necrotic pulp tissue in the root canal system is not accessible to the host's innate and adaptive immune defense mechanisms and antimicrobial agents. Therefore, the infected or non-infected necrotic pulp tissue must be removed from the canal space by pulpectomy. As our knowledge in pulp biology advances, the concept of treatment of pulpal and periapical disease also changes. Endodontists have been looking for biologically based treatment procedures, which could promote regeneration or repair of the dentin-pulp complex destroyed by infection or trauma for several decades. After a long, extensive search in in vitro laboratory and in vivo preclinical animal experiments, the dental stem cells capable of regenerating the dentin-pulp complex were discovered. Consequently, the biological concept of ‘regenerative endodontics’ emerged and has highlighted the paradigm shift in the treatment of immature permanent teeth with necrotic pulps in clinical endodontics. Regenerative endodontics is defined as biologically based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as the pulp-dentin complex. According to the American Association of Endodontists’ Clinical Considerations for a Regenerative Procedure, the primary goal of the regenerative procedure is the elimination of clinical symptoms and the resolution of apical periodontitis. Thickening of canal walls and continued root maturation is the secondary goal. Therefore, the primary goal of regenerative endodontics and traditional non-surgical root canal therapy is the same. The difference between non-surgical root canal therapy and regenerative endodontic therapy is that the disinfected root canals

Regulators of pluripotency and their implications in regenerative medicine

Directory of Open Access Journals (Sweden)

El-Badawy A

2015-04-01

Full Text Available Ahmed El-Badawy, Nagwa El-Badri Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, Egypt Abstract: 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. Keywords: dedifferentiation, transdifferentiation, reprogramming, pluripotency, microRNAs, epigenetic modifications, signaling pathways, toll-like receptors

Induced pluripotent stem cells for regenerative cardiovascular therapies and biomedical discovery.

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Nsair, Ali; MacLellan, W Robb

2011-04-30

The discovery of induced pluripotent stem cells (iPSC) has, in the short time since their discovery, revolutionized the field of stem cell biology. This technology allows the generation of a virtually unlimited supply of cells with pluripotent potential similar to that of embryonic stem cells (ESC). However, in contrast to ESC, iPSC are not subject to the same ethical concerns and can be easily generated from living individuals. For the first time, patient-specific iPSC can be generated and offer a supply of genetically identical cells that can be differentiated into all somatic cell types for potential use in regenerative therapies or drug screening and testing. As the techniques for generation of iPSC lines are constantly evolving, new uses for human iPSC are emerging from in-vitro disease modeling to high throughput drug discovery and screening. This technology promises to revolutionize the field of medicine and offers new hope for understanding and treatment of numerous diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

Tissue Engineering in Regenerative Dental Therapy

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Hiral Jhaveri-Desai

2011-01-01

Full Text Available Tissue engineering is amongst the latest exciting technologies having impacted the field of dentistry. Initially considered as a futuristic approach, tissue engineering is now being successfully applied in regenerative surgery. This article reviews the important determinants of tissue engineering and how they contribute to the improvement of wound healing and surgical outcomes in the oral region. Furthermore, we shall address the clinical applications of engineering involving oral and maxillofacial surgical and periodontal procedures along with other concepts that are still in experimental phase of development. This knowledge will aid the surgical and engineering researchers to comprehend the collaboration between these fields leading to extounding dental applications and to ever-continuing man-made miracles in the field of human science.

Stem Cells in Regenerative Medicine

OpenAIRE

Sykova, Eva; Forostyak, Serhiy

2013-01-01

Background: A number of cardiovascular, neurological, musculoskeletal and other diseases have a limited capacity for repair and only a modest progress has been made in treatment of brain diseases. The discovery of stem cells has opened new possibilities for the treatment of these maladies, and cell therapy now stands at the cutting-edge of modern regenerative medicine and tissue engineering. Experimental data and the first clinical trials employing stem cells have shown their broad therapeuti...

The interplay of post-translational modification and gene therapy

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Osamor VC

2016-02-01

Full Text Available Victor Chukwudi Osamor,1–3 Shalom N Chinedu,3,4 Dominic E Azuh,3,5 Emeka Joshua Iweala,3,4 Olubanke Olujoke Ogunlana3,4 1Covenant University Bioinformatics Research (CUBRe Unit, Department of Computer and Information Sciences, College of Science and Technology (CST, Covenant University, Ota, Ogun State, Nigeria; 2Institute of Informatics (Computational biology and Bioinformatics, Faculty of Mathematics, Informatics and Mechanics, University of Warsaw (Uniwersytet Warszawski, Warszawa, Poland; 3Covenant University Public Health and Well-being Research Group (CUPHWERG, Covenant University, 4Biochemistry and Molecular Biology Unit, Department of Biological Sciences, College of Science and Technology, Covenant University, Canaan Land, 5Department of Economics and Development Studies, Covenant University, Ota, Ogun State, Nigeria Abstract: Several proteins interact either to activate or repress the expression of other genes during transcription. Based on the impact of these activities, the proteins can be classified into readers, modifier writers, and modifier erasers depending on whether histone marks are read, added, or removed, respectively, from a specific amino acid. Transcription is controlled by dynamic epigenetic marks with serious health implications in certain complex diseases, whose understanding may be useful in gene therapy. This work highlights traditional and current advances in post-translational modifications with relevance to gene therapy delivery. We report that enhanced understanding of epigenetic machinery provides clues to functional implication of certain genes/gene products and may facilitate transition toward revision of our clinical treatment procedure with effective fortification of gene therapy delivery. Keywords: post-translational modification, gene therapy, epigenetics, histone, methylation

Caenorhabditis elegans in regenerative medicine: a simple model for a complex discipline.

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Aitlhadj, Layla; Stürzenbaum, Stephen R

2014-06-01

Stem cell research is a major focus of regenerative medicine, which amalgamates diverse disciplines ranging from developmental cell biology to chemical and genetic therapy. Although embryonic stem cells have provided the foundation of stem cell therapy, they offer an in vitro study system that might not provide the best insight into mechanisms and behaviour of cells within living organisms. Caenorhabditis elegans is a well defined model organism with highly conserved cell development and signalling processes that specify cell fate. Its genetic amenability coupled with its chemical screening applicability make the nematode well suited as an in vivo system in which regenerative therapy and stem cell processes can be explored. Here, we describe some of the major advances in stem cell research from the worm's perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recommendations for using regenerative endodontic procedures in permanent immature traumatized teeth.

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Garcia-Godoy, Franklin; Murray, Peter E

2012-02-01

The regeneration of immature permanent teeth following trauma could be beneficial to reduce the risk of fracture and loss of millions of teeth each year. Regenerative endodontic procedures include revascularization, partial pulpotomy, and apexogenesis. Several case reports give these procedures a good prognosis as an alternative to apexification. Care is needed to deliver regenerative endodontic procedures that maintain or restore the vitality of teeth, but which also disinfect and remove necrotic tissues. Regeneration can be accomplished through the activity of the cells from the pulp, periodontium, vascular, and immune system. Most therapies use the host's own pulp or vascular cells for regeneration, but other types of dental stem cell therapies are under development. There are no standardized treatment protocols for endodontic regeneration. The purpose of this article is to review the recent literature and suggest guidelines for using regenerative endodontic procedures for the treatment of permanent immature traumatized teeth. Recommendations for the selection of regenerative and conventional procedures based on the type of tooth injury, fracture type, presence of necrosis or infection, periodontal status, presence of periapical lesions, stage of tooth development, vitality status, patient age, and patient health status will be reviewed. Because of the lack of long-term evidence to support the use of regenerative endodontic procedures in traumatized teeth with open apices, revascularization regeneration procedures should only be attempted if the tooth is not suitable for root canal obturation, and after apexogenesis, apexification, or partial pulpotomy treatments have already been attempted and have a poor prognosis. © 2011 John Wiley & Sons A/S.

Regenerative endodontics and tissue engineering: what the future holds?

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Goodis, Harold E; Kinaia, Bassam Michael; Kinaia, Atheel M; Chogle, Sami M A

2012-07-01

The work performed by researchers in regenerative endodontics and tissue engineering over the last decades has been superb; however, many questions remain to be answered. The basic biologic mechanisms must be elucidated that will allow the development of dental pulp and dentin in situ. Stress must be placed on the many questions that will lead to the design of effective, safe treatment options and therapies. This article discusses those questions, the answers to which may become the future of regenerative endodontics. The future remains bright, but proper support and patience are required. Copyright © 2012 Elsevier Inc. All rights reserved.

Personalized Regenerative Medicine

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Babak Arjmand

2017-03-01

Full Text Available 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.

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal.

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Hettle, Robert; Corbett, Mark; Hinde, Sebastian; Hodgson, Robert; Jones-Diette, Julie; Woolacott, Nerys; Palmer, Stephen

2017-02-01

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. 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. 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-cell transplantation

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

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Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W; Wolf, Matthew T; Fan, Hongni; Tam, Ada J; Patel, Chirag H; Luber, Brandon S; Wang, Hao; Wagner, Kathryn R; Powell, Jonathan D; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

2016-04-15

Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. Copyright © 2016, American Association for the Advancement of Science.

Dental pulp stem cells in regenerative dentistry.

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Casagrande, Luciano; Cordeiro, Mabel M; Nör, Silvia A; Nör, Jacques E

2011-01-01

Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

Regenerative endodontics: A way forward.

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Diogenes, Anibal; Ruparel, Nikita B; Shiloah, Yoav; Hargreaves, Kenneth M

2016-05-01

Immature teeth are susceptible to infections due to trauma, anatomic anomalies, and caries. Traditional endodontic therapies for immature teeth, such as apexification procedures, promote resolution of the disease and prevent future infections. However, these procedures fail to promote continued root development, leaving teeth susceptible to fractures. Regenerative endodontic procedures (REPs) have evolved in the past decade, being incorporated into endodontic practice and becoming a viable treatment alternative for immature teeth. The authors have summarized the status of regenerative endodontics on the basis of the available published studies and provide insight into the different levels of clinical outcomes expected from these procedures. Substantial advances in regenerative endodontics are allowing a better understanding of a multitude of factors that govern stem cell-mediated regeneration and repair of the damaged pulp-dentin complex. REPs promote healing of apical periodontitis, continued radiographic root development, and, in certain cases, vitality responses. Despite the clinical success of these procedures, they appear to promote a guided endodontic repair process rather than a true regeneration of physiological-like tissue. Immature teeth with pulpal necrosis with otherwise poor prognosis can be treated with REPs. These procedures do not preclude the possibility of apexification procedures if attempts are unsuccessful. Therefore, REPs may be considered first treatment options for immature teeth with pulpal necrosis. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering.

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Ogueri, Kenneth S; Escobar Ivirico, Jorge L; Nair, Lakshmi S; Allcock, Harry R; Laurencin, Cato T

2017-03-01

The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately, be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly (lactide-co-glycolide) (PLAGA). Laurencin and co-workers has demonstrated the exploitation of the synthetic flexibility of Polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of this new

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

Science.gov (United States)

Ogueri, Kenneth S.; Escobar Ivirico, Jorge L.; Nair, Lakshmi S.; Allcock, Harry R.; Laurencin, Cato T.

2017-01-01

The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately, be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly (lactide-co-glycolide) (PLAGA). Laurencin and co-workers has demonstrated the exploitation of the synthetic flexibility of Polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Lay Summary Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of

Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue.

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Perez, Roman A; Jung, Cho-Rok; Kim, Hae-Won

2017-01-01

Regenerative approach has emerged to substitute the current extracorporeal technologies for the treatment of diseased and damaged liver tissue. This is based on the use of biomaterials that modulate the responses of hepatic cells through the unique matrix properties tuned to recapitulate regenerative functions. Cells in liver preserve their phenotype or differentiate through the interactions with extracellular matrix molecules. Therefore, the intrinsic properties of the engineered biomaterials, such as stiffness and surface topography, need to be tailored to induce appropriate cellular functions. The matrix physical stimuli can be combined with biochemical cues, such as immobilized functional groups or the delivered actions of signaling molecules. Furthermore, the external modulation of cells, through cocultures with nonparenchymal cells (e.g., endothelial cells) that can signal bioactive molecules, is another promising avenue to regenerate liver tissue. This review disseminates the recent approaches of regenerating liver tissue, with a focus on the development of biomaterials and the related culture technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human dental pulp stem cells: Applications in future regenerative medicine

Science.gov (United States)

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

Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases.

Science.gov (United States)

Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J

2013-10-01

Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety. © 2013 American Physiological Society. Compr Physiol 3:1749-1779, 2013.

Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone

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Adrian Tudor Balseanu

2014-06-01

Full Text Available Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF. We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg or in combination with a single dose (106 cells of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies

Introduction to regenerative medicine and tissue engineering.

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Stoltz, J-F; Decot, V; Huseltein, C; He, X; Zhang, L; Magdalou, J; Li, Y P; Menu, P; Li, N; Wang, Y Y; de Isla, N; Bensoussan, D

2012-01-01

Human tissues don't regenerate spontaneously, explaining why regenerative medicine and cell therapy represent a promising alternative treatment (autologous cells or stem cells of different origins). The principle is simple: cells are collected, expanded and introduced with or without modification into injured tissues or organs. Among middle-term therapeutic applications, cartilage defects, bone repair, cardiac insufficiency, burns, liver or bladder, neurodegenerative disorders could be considered.

The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine.

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Nagashima, Shunta; Bao, Yijun; Hata, Yutaka

2017-01-01

Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Regenerative therapies for equine degenerative joint disease: a preliminary study.

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Sarah Broeckx

Full Text Available Degenerative joint disease (DJD is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP and mesenchymal stem cells (MSCs were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1 PRP; 2 MSCs; 3 MSCs and PRP; or 4 chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1, 12 weeks (T2, 6 months (T3 and 12 months (T4 post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC II and p63, low in MHC I and positive for Ki67, collagen type II (Col II and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment.

Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

DEFF Research Database (Denmark)

Koch, Thomas Gadegaard; Berg, Lise Charlotte; 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...... 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...

Regenerative nanotechnology in oral and maxillofacial surgery.

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Shakib, Kaveh; Tan, Aaron; Soskic, Vukic; Seifalian, Alexander M

2014-12-01

Regenerative nanotechnology is at the forefront of medical research, and translational medicine is a challenge to both scientists and clinicians. Although there has been an exponential rise in the volume of research generated about it for both medical and surgical uses, key questions remain about its actual benefits. Nevertheless, some people think that therapeutics based on its principles may form the core of applied research for the future. Here we give an account of its current use in oral and maxillofacial surgery, and implications and challenges for the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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

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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. © 2014 Blackwell Verlag GmbH.

Regenerative endodontics: A state of the art

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Rashmi Bansal

2011-01-01

Full Text Available Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue grafting, tissue engineering, molecular biology and the human genome project provide the basis for the introduction of new technologies into dentistry. Non-vital infected teeth have long been treated with root canal therapy (for mature root apex and apexification (for immature root apex, or doomed to extraction. Although successful, current treatments fail to re-establish healthy pulp tissue in these teeth. But, what if the non-vital tooth could be made vital once again? That is the hope offered by regenerative endodontics, an emerging field focused on replacing traumatized and diseased pulp with functional pulp tissue. Restoration of vitality of non-vital tooth is based on tissue engineering and revascularization procedures. The purpose of this article is to review these biological procedures and the hurdles that must be overcome to develop regenerative endodontic procedures.

Clinical translation of stem cell therapy in traumatic brain injury: the potential of encapsulated mesenchymal cell biodelivery of glucagon-like peptide-1

OpenAIRE

Heile, Anna; Brinker, Thomas

2011-01-01

Traumatic brain injury remains a major cause of death and disability; it is estimated that annually 10 million people are affected. Preclinical studies have shown the potential therapeutic value of stem cell therapies. Neuroprotective as well as regenerative properties of stem cells have been suggested to be the mechanism of action in preclinical studies. However, up to now stem cell therapy has not been studied extensively in clinical trials. This article summarizes the current experimental ...

Cardiovascular disease: primary prevention, disease modulation and regenerative therapy.

LENUS (Irish Health Repository)

Sultan, Sherif

2012-10-01

Cardiovascular primary prevention and regeneration programs are the contemporary frontiers in functional metabolic vascular medicine. This novel science perspective harnesses our inherent ability to modulate the interface between specialized gene receptors and bioavailable nutrients in what is labeled as the nutrient-gene interaction. By mimicking a natural process through the conveyance of highly absorbable receptor specific nutrients, it is feasible to accelerate cell repair and optimize mitochondrial function, thereby achieving cardiovascular cure. We performed a comprehensive review of PubMed, EMBASE and Cochrane Review databases for articles relating to cardiovascular regenerative medicine, nutrigenomics and primary prevention, with the aim of harmonizing their roles within contemporary clinical practice. We searched in particular for large-scale randomized controlled trials on contemporary cardiovascular pharmacotherapies and their specific adverse effects on metabolic pathways which feature prominently in cardiovascular regenerative programs, such as nitric oxide and glucose metabolism. Scientific research on \\'cardiovascular-free\\' centenarians delineated that low sugar and low insulin are consistent findings. As we age, our insulin level increases. Those who can decelerate the rapidity of this process are prompting their cardiovascular rejuvenation. It is beginning to dawn on some clinicians that contemporary treatments are not only failing to impact on our most prevalent diseases, but they may be causing more damage than good. Primary prevention programs are crucial elements for a better outcome. Cardiovascular primary prevention and regeneration programs have enhanced clinical efficacy and quality of life and complement our conventional endovascular practice.

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

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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.

Regenerative endodontics.

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Simon, S; Smith, A J

2014-03-01

Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

Micro-computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model

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Khobragade, P.; Jain, A.; Setlur Nagesh, S. V.; Andreana, S.; Dziak, R.; Sunkara, S. K.; Sunkara, S.; Bednarek, D. R.; Rudin, S.; Ionita, C. N.

2015-03-01

High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custombuilt micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor invivo bone regeneration studies for greater regenerative process understanding.

Cell and Gene Therapies: European View on Challenges in Translation and How to Address Them

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Cécile F. Rousseau

2018-05-01

Full Text Available Advanced therapy medicinal products (ATMPs, i.e., cell and gene therapy products, is a rapidly evolving field of therapeutic development. A significant proportion of the products are being developed by academia or small/medium-sized enterprises (SMEs. The many challenges in translation posed by this class of products include aspects covering: manufacturing, non-clinical development plan as relevant to clinical trial, marketing authorization, and reimbursement. In this context, the term translation refers to the relevance of non-clinical data in relation to how it impacts on appropriate and efficient clinical development. In order to successfully overcome these challenges, a clear understanding of the requirements and expectations of all the stakeholders is critical. This article aims to cover the potential challenges related to such translation and suggested approaches to find solutions based on experience and learnings from the perspective of European Union. While commercial challenges have a significant impact on the ATMPs in general, it is considered outside the scope of this article. However, by adopting a strong scientific basis for translation as suggested in this article, it is likely such an approach would help rather than harm successful real world clinical use of ATMPs.

Researchers and the translational reality. Interview with Karen Aboody.

Science.gov (United States)

Aboody, Karen

2012-11-01

Karen Aboody has first-hand experience of taking a potential therapy from the laboratory into clinical trials. Here, she shares with us the challenges and rewards of going from bench to bedside, and why all biomedical researchers need to know what it takes to make the transition if they want the best chance of seeing their discoveries used to help patients. Karen Aboody received her MD at Mount Sinai School of Medicine, and completed her post-doctoral training in Molecular Neurogenetics at Massachusetts General Hospital, Harvard Medical School. After gaining experience in pathology, gene therapy and biotechnology, she joined City of Hope (COH) in 2003 to head a translational research laboratory focused on therapeutic stem cell applications for invasive and metastatic solid tumors. In 2010, she received US FDA approval for a first-in-human clinical trial for neural stem cell-mediated therapy for high-grade glioma patients. This Phase I study is ongoing at COH, supported by NCI/NIH funding. In 2010, she received an US$18 million California Institute of Regenerative Medicine Disease Team Award to develop a second-generation enzyme/prodrug stem cell-mediated brain tumor therapy for clinical trials that may also have applications for other metastatic cancers. Honors include the 2000 AANS Young Investigator Award, and 2008 ASGCT Outstanding New Investigator Award. She recently founded a clinical-stage biopharmaceutical company, TheraBiologics Inc., to support clinical development of neural stem cell-mediated cancer therapies.

Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

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Tam, Roger Y; Fuehrmann, Tobias; Mitrousis, Nikolaos; Shoichet, Molly S

2014-01-01

The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood–brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair. PMID:24002187

Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology.

Science.gov (United States)

Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

2011-06-01

Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology.

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Jadczyk, T; Faulkner, A; Madeddu, P

2013-05-01

Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Ethical and Safety Issues of Stem Cell-Based Therapy.

Science.gov (United States)

Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

2018-01-01

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

Regenerative similariton laser

Directory of Open Access Journals (Sweden)

Thibault North

2016-05-01

Full Text Available Self-pulsating lasers based on cascaded reshaping and reamplification (2R are capable of initiating ultrashort pulses despite the accumulation of large amounts of nonlinearities in all-fiber resonators. The spectral properties of pulses in self-similar propagation are compatible with cascaded 2R regeneration by offset filtering, making parabolic pulses suitable for the design of a laser of this recently introduced class. A new type of regenerative laser giving birth to similaritons is numerically investigated and shows that this laser is the analog of regenerative sources based solely on self-phase modulation and offset filtering. The regenerative similariton laser does not suffer from instabilities due to excessive nonlinearities and enables ultrashort pulse generation in a simple cavity configuration.

Regenerative endodontic treatment for necrotic immature permanent premolar: A report of case

Directory of Open Access Journals (Sweden)

Sheetal B Ghivari

2017-01-01

Full Text Available Regenerative endodontic procedures provide new hope of converting nonvital tooth into vital once again. These potential regenerative approaches include root canal revascularization, postnatal stem-cell therapy, pulp implant, scaffold implant, three-dimensional cell printing, injectable scaffolds, and gene therapy. In this article, we describe successful revascularization treatment of necrotic permanent premolar tooth. Clinical and radiographic examination showed pulp involvement due to deep pit defect and periapical infection. Examination findings suggested revascularization treatment which was started with irrigation of canals using 1.25% of sodium hypochlorite and saline, followed by placement of 3-week dressing of triple antibiotic paste (ciprofloxacin, metronidazole, and minocycline. After removal of triple antibiotic paste blood clot was induced and mineral trioxide aggregate was placed on the blood clot followed by sealing the canal with glass ionomer cement. During radiographic and clinical follow-ups, the patient was asymptomatic and periapical lesion was healed, roots continued to develop, and root apex maturogenesis was complete.

Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine.

Science.gov (United States)

Skeldon, Gregor; Lucendo-Villarin, Baltasar; Shu, Wenmiao

2018-07-05

Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Author(s).

Regenerative rehabilitation: a new future?

Science.gov (United States)

Perez-Terzic, Carmen; Childers, Martin K

2014-11-01

Modern rehabilitation medicine is propelled by newfound knowledge aimed at offering solutions for an increasingly aging population afflicted by chronic debilitating conditions. Considered a core component of future health care, the rollout of regenerative medicine underscores a paradigm shift in patient management targeted at restoring physiologic function and restituting normative impact. Nascent regenerative technologies offer unprecedented prospects in achieving repair of degenerated, diseased, or damaged tissues. In this context, principles of regenerative science are increasingly integrated in rehabilitation practices as illustrated in the present Supplement. Encompassing a growing multidisciplinary domain, the emergent era of "regenerative rehabilitation" brings radical innovations at the forefront of healthcare blueprints.

Surgical Non-Regenerative Treatments for Peri-Implantitis: a Systematic Review

Directory of Open Access Journals (Sweden)

Ausra Ramanauskaite

2016-09-01

Full Text Available Objectives: The purposes of the present study were 1 to systematically review the literature on the surgical non-regenerative treatments of peri-implantitis and 2 to determine a predictable therapeutic option for the clinical management of peri-implantitis lesions. Material and Methods: The study search was performed on primary database MEDLINE and EMBASE from 2005 until 2016. Sequential screenings at the title, abstract, and full-text levels were performed. Clinical human studies in the English language that had reported changes in probing depth (PD and/or bleeding on probing (BOP and/or radiologic marginal bone level changes after peri-implantitis surgical non-regenerative treatment at 6-month follow-up or longer were included accordingly PRISMA guidelines. Results: The first electronic and hand search resulted in 765 citations. From 16 full-text articles reviewed, 6 were included in this systematic review. Surgical non-regenerative methods were found to be efficient in reducing clinical parameters. BOP and PD values were significantly decreased following implantoplasty and systematic administration of antibacterials, but not after local application of chemical compounds or diode laser. Similarly, significant improvement in clinical and radiographic parameters was found only after implantoplasty compared with resective surgery alone. We found significant heterogeneity in study designs and treatments provided among the pooled studies. All of the studies revealed an unclear or high risk of bias. Conclusions: Surgical non-regenerative treatment of peri-implantitis was found to be effective to reduce the soft tissue inflammation and decrease probing depth. More randomized controlled clinical trials are needed to assess the efficacy of surgical non-regenerative therapy of peri-implantitis.

Scaffolds in regenerative endodontics: A review

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Gathani, Kinjal M.; Raghavendra, Srinidhi Surya

2016-01-01

Root canal therapy has enabled us to save numerous teeth over the years. The most desired outcome of endodontic treatment would be when diseased or nonvital pulp is replaced with healthy pulp tissue that would revitalize the teeth through regenerative endodontics. ‘A search was conducted using the Pubmed and MEDLINE databases for articles with the criteria ‘Platelet rich plasma’, ‘Platelet rich fibrin’, ‘Stem cells’, ‘Natural and artificial scaffolds’ from 1982–2015’. Tissues are organized as three-dimensional structures, and appropriate scaffolding is necessary to provide a spatially correct position of cell location and regulate differentiation, proliferation, or metabolism of the stem cells. Extracellular matrix molecules control the differentiation of stem cells, and an appropriate scaffold might selectively bind and localize cells, contain growth factors, and undergo biodegradation over time. Different scaffolds facilitate the regeneration of different tissues. To ensure a successful regenerative procedure, it is essential to have a thorough and precise knowledge about the suitable scaffold for the required tissue. This article gives a review on the different scaffolds providing an insight into the new developmental approaches on the horizon. PMID:27857762

Scaffolds in regenerative endodontics: A review

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Kinjal M Gathani

2016-01-01

Full Text Available Root canal therapy has enabled us to save numerous teeth over the years. The most desired outcome of endodontic treatment would be when diseased or nonvital pulp is replaced with healthy pulp tissue that would revitalize the teeth through regenerative endodontics. ′A search was conducted using the Pubmed and MEDLINE databases for articles with the criteria ′Platelet rich plasma′, ′Platelet rich fibrin′, ′Stem cells′, ′Natural and artificial scaffolds′ from 1982-2015′. Tissues are organized as three-dimensional structures, and appropriate scaffolding is necessary to provide a spatially correct position of cell location and regulate differentiation, proliferation, or metabolism of the stem cells. Extracellular matrix molecules control the differentiation of stem cells, and an appropriate scaffold might selectively bind and localize cells, contain growth factors, and undergo biodegradation over time. Different scaffolds facilitate the regeneration of different tissues. To ensure a successful regenerative procedure, it is essential to have a thorough and precise knowledge about the suitable scaffold for the required tissue. This article gives a review on the different scaffolds providing an insight into the new developmental approaches on the horizon.

Application of Stem Cell Technology in Dental Regenerative Medicine.

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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.

Adipose tissue-derived stem cells in neural regenerative medicine.

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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.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

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Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Jhaveri, Hiral M. [Department of Periodontics and Oral Implantology, Dr. D.Y. Patil Dental College and Hospital, Pune (India); Mishra, Gyan C. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

2010-03-12

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

International Nuclear Information System (INIS)

Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T.; Jhaveri, Hiral M.; Mishra, Gyan C.; Wani, Mohan R.

2010-01-01

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

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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

Neural stem/progenitor cells as a promising candidate for regenerative therapy of the central nervous system

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Virginie eBonnamain

2012-04-01

Full Text Available Neural transplantation is a promising therapeutic strategy for neurodegenerative diseases and other affections of the central nervous system (CNS like Parkinson and Huntington diseases, multiple sclerosis or stroke. If cell replacement therapy already went through clinical trials for some of these diseases using fetal human neuroblasts, several important limitations led to the search for alternative cell sources that would be more suitable for intracerebral transplantation. Taking into account logistical and ethical issues linked to the use of tissue derived from human fetuses, and the immunologically special status of the CNS allowing the occurrence of deleterious immune reactions, Neural Stem/Progenitor Cells (NSPCs appear as an interesting cell source candidate. In addition to their ability for replacing cell populations lost during the pathological events, NSPCs also display surprising therapeutic effects of neuroprotection and immunomodulation. A better knowledge of the mechanisms involved in these specific characteristics will hopefully lead in the future to a successful use of NSPCs in regenerative medicine for CNS affections.

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

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2013-07-22

... regenerative medicine products have generated a great deal of interest. These efforts include standards... is done to coordinate the various existing efforts. In the public workshop, FDA hopes to bring...

Regenerative medicine in dental and oral tissues: Dental pulp mesenchymal stem cell

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Janti Sudiono

2017-08-01

Full Text Available Background. Regenerative medicine is a new therapeutic modality using cell, stem cell and tissue engineering technologies. Purpose. To describe the regenerative capacity of dental pulp mesenchymal stem cell. Review. In dentistry, stem cell and tissue engineering technologies develop incredibly and attract great interest, due to the capacity to facilitate innovation in dental material and regeneration of dental and oral tissues. Mesenchymal stem cells derived from dental pulp, periodontal ligament and dental follicle, can be isolated, cultured and differentiated into various cells, so that can be useful for regeneration of dental, nerves, periodontal and bone tissues. Tissue engineering is a technology in reconstructive biology, which utilizes mechanical, cellular, or biological mediators to facilitate regeneration or reconstruction of a particular tissue. The multipotency, high proliferation rates and accessibility, make dental pulp as an attractive source of mesenchymal stem cells for tissue regeneration. Revitalized dental pulp and continued root development is the focus of regenerative endodontic while biological techniques that can restore lost alveolar bone, periodontal ligament, and root cementum is the focus of regenerative periodontic. Conclucion. Dentin-derived morphogens such as BMP are known to be involved in the regulation of odontogenesis. The multipotency and angiogenic capacity of DPSCs as the regenerative capacity of human dentin / pulp complex indicated that dental pulp may contain progenitors that are responsible for dentin repair. The human periodontal ligament is a viable alternative source for possible primitive precursors to be used in stem cell therapy.

Regenerative medicine in India: trends and challenges in innovation and regulation.

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Tiwari, Shashank S; Raman, Sujatha; Martin, Paul

2017-10-01

The government of India has heavily promoted research and development in regenerative medicine together with domestic innovation and business development initiatives. Together, these promise a revolution in healthcare and public empowerment in India. Several national and transnational linkages have emerged to develop innovative capacity, most prominently in stem cell and cord blood banking, as well as in gene therapy, tissue engineering, biomaterials and 3D printing. However, challenges remain of achieving regulatory oversight, viable outputs and equitable impacts. Governance of private cord blood banking, nanomaterials and 3D bioprinting requires more attention. A robust social contract is also needed in healthcare more generally, so that participation in research and innovation in regenerative medicine is backed up by treatments widely accessible to all.

Why regenerative medicine needs an extracellular matrix.

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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.

Phenylketonuria: translating research into novel therapies

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Ho, Gladys

2014-01-01

Phenylketonuria (PKU) is an inborn error of metabolism of the amino acid phenylalanine. It is an autosomal recessive disorder with a rate of incidence of 1 in 10,000 in Caucasian populations. Mutations in the phenylalanine hydroxylase (PAH) gene are the major cause of PKU, due to the loss of the catalytic activity of the enzyme product PAH. Newborn screening for PKU allows early intervention, avoiding irreparable neurological damage and intellectual disability that would arise from untreated PKU. The current primary treatment of PKU is the limitation of dietary protein intake, which in the long term may be associated with poor compliance in some cases and other health problems due to malnutrition. The only alternative therapy currently approved is the supplementation of BH4, the requisite co-factor of PAH, in the orally-available form of sapropterin dihydrochloride. This treatment is not universally available, and is only effective for a proportion (estimated 30%) of PKU patients. Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents. It is hoped that continuing efforts into these studies will translate into a significant improvement in the physical outcome, as well as quality of life, for patients with PKU. PMID:26835324

Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy

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Mosca, Rodrigo Crespo

2014-01-01

The neoplasms incidence has increased significantly in recent years and continued population growth and aging will increase the statistics of this illness in the world's diseases. The cancer treatment usually consists in individual or combined use of chemotherapy, surgery and radiotherapy depending on the etiology of the tumor. In cases where radiotherapy is used in addition to the therapeutic effects of radiation, specific complications can occur, and in the skin, these complications can be present with a clinical expression ranging from erythema to radionecrosis, and this latter being the adverse effect with greater severity. The radionecrosis treatment consists in debridement necrotic areas and covering the surgical wounds. Autologous grafts are most commonly used for this covering, however when large areas are affected, allografts can be used for occlusive treatment and the keratinocytes and adipose derived stem cells (ADSC) addition becomes an alternative, due to the knowing for immunomodulatory and regenerative response. For that reason, aiming to simulate the radionecrosis adverse effects, an animal model of induced cutaneous radionecrosis was created, in athymic mouse Nude (Nu/Nu), for developing regenerative therapies based on human dermal-epidermal substitutes containing keratinocytes and ADSC, which proved occlusive as an efficient treatment, furthermore, having this radionecrosis animal model established, new possibilities for treatment of diseases involving dermal regeneration, can be tested. (author)

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

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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. Copyright © 2015 John Wiley & Sons, Ltd.

Potential sources of stem cells as a regenerative therapy for Parkinson's disease

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Abir Oueida El-Sadik

2010-12-01

Full Text Available Abir Oueida El-SadikDepartment of Anatomy and Embryology, Scientific Research Unit, Female Health Science College, King Saud University, Riyadh, Kingdom of Saudi ArabiaAbstract: Stem cells are believed to hold enormous promise as potential replacement therapy in the treatment of neurodegenerative diseases such as Parkinson's disease (PD. Stem cells were investigated to be the alternative therapeutic source capable of differentiating into dopamine (DA neurons. Multiple important signaling factors were recorded for the induction of DA neuronal traits from mouse embryonic stem cells (ESCs such as fibroblast growth factor 8, sonic hedgehog, and Wnt 1. Recent protocols were described for the differentiation of human ESCs into DA neurons, achieving high efficiency of DA neuronal derivation. Despite that, the use of human ESCs is still ethically controversial. The transcription factors necessary for DA neuron development from adult neural stem cells (NSCs, such as Pitx3, Nurr1, En-1, En-2, Lmx1a, Lmx1b, Msx1, and Ngn2, were investigated. In addition to replacement of lost DA neurons, adult NSCs were recorded to provide neuroprotective and neurogenic factors for the mesencephalon. In addition, induced pluripotent stem cells and bone marrow-derived mesenchymal stem cells represent reliable stem cell sources of DA neurons. Future studies are recommended to provide further insight into the regenerative capacity of stem cells needed for the treatment of PD.Keywords: dopamine, embryonic stem cells, neural stem cells, Parkinson's disease, induced pluripotent stem cells, mesenchymal stem cells

REGEN: Ancestral Genome Reconstruction for Bacteria.

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Yang, Kuan; Heath, Lenwood S; Setubal, João C

2012-07-18

Ancestral genome reconstruction can be understood as a phylogenetic study with more details than a traditional phylogenetic tree reconstruction. We present a new computational system called REGEN for ancestral bacterial genome reconstruction at both the gene and replicon levels. REGEN reconstructs gene content, contiguous gene runs, and replicon structure for each ancestral genome. Along each branch of the phylogenetic tree, REGEN infers evolutionary events, including gene creation and deletion and replicon fission and fusion. The reconstruction can be performed by either a maximum parsimony or a maximum likelihood method. Gene content reconstruction is based on the concept of neighboring gene pairs. REGEN was designed to be used with any set of genomes that are sufficiently related, which will usually be the case for bacteria within the same taxonomic order. We evaluated REGEN using simulated genomes and genomes in the Rhizobiales order.

Regenerative liver surgeries: the alphabet soup of emerging techniques.

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Parekh, Maansi; Kluger, Michael D; Griesemer, Adam; Bentley-Hibbert, Stuart

2016-01-01

New surgical procedures taking advantage of the regenerative abilities of the liver are being introduced as potential curative therapies to these patients either to provide auxiliary support while the native liver recovers or undergoes hypertrophy. For patients with hepatocellular carcinoma outside of the Milan criteria or bilobar colorectal metastases liver transplantation is not an option. Fulminant hepatic failure can be treated but requires life-long immunosuppression. These complex surgical procedures require high quality and directed imaging.

Regenerative Medicine for Neurological Disorders

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Dong-Hyuk Park

2010-01-01

Full Text Available 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.

Concise review: reprogramming strategies for cardiovascular regenerative medicine: from induced pluripotent stem cells to direct reprogramming.

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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.

MSCs-derived exosomes: cell-secreted nanovesicles with regenerative potential

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Ana Marote

2016-08-01

Full Text Available Exosomes are membrane-enclosed nanovesicles (30-150 nm that shuttle active cargoes between different cells. These tiny extracellular vesicles have been recently isolated from mesenchymal stem cells (MSCs conditioned medium, a population of multipotent cells identified in several adult tissues. MSCs paracrine activity has been already shown to be the key mediator of their elicited regenerative effects. On the other hand, the individual contribution of MSCs-derived exosomes for these effects is only now being unraveled. The administration of MSCs-derived exosomes has been demonstrated to restore tissue function in multiple diseases/injury models and to induce beneficial in vitro effects, mainly mediated by exosomal-enclosed miRNAs. Additionally, the source and the culture conditions of MSCs have been shown to influence the regenerative responses induced by exosomes. Therefore, these studies reveal that MSCs-derived exosomes hold a great potential for cell-free therapies that are safer and easier to manipulate than cell-based products. Nevertheless, this is an emerging research field and hence, further studies are required to understand the full dimension of this complex intercellular communication system and how it can be optimized to take full advantage of its therapeutic effects. In this mini-review, we summarize the most significant new advances in the regenerative properties of MSCs-derived exosomes and discuss the molecular mechanisms underlying these effects.

REGEN: Ancestral Genome Reconstruction for Bacteria

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João C. Setubal

2012-07-01

Full Text Available Ancestral genome reconstruction can be understood as a phylogenetic study with more details than a traditional phylogenetic tree reconstruction. We present a new computational system called REGEN for ancestral bacterial genome reconstruction at both the gene and replicon levels. REGEN reconstructs gene content, contiguous gene runs, and replicon structure for each ancestral genome. Along each branch of the phylogenetic tree, REGEN infers evolutionary events, including gene creation and deletion and replicon fission and fusion. The reconstruction can be performed by either a maximum parsimony or a maximum likelihood method. Gene content reconstruction is based on the concept of neighboring gene pairs. REGEN was designed to be used with any set of genomes that are sufficiently related, which will usually be the case for bacteria within the same taxonomic order. We evaluated REGEN using simulated genomes and genomes in the Rhizobiales order.

Changes in Regenerative Capacity through Lifespan

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Maximina H. Yun

2015-10-01

Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

Regenerative Rehabilitation – a New Future?

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Perez-Terzic, Carmen; Childers, Martin K.

2014-01-01

Modern rehabilitation medicine is propelled by newfound knowledge aimed at offering solutions for an increasingly aging population afflicted by chronic debilitating conditions. Considered a core component of future healthcare, the roll-out of regenerative medicine underscores a paradigm shift in patient management targeted at restoring physiologic function and restituting normative impact. Nascent regenerative technologies offer unprecedented prospects in achieving repair of degenerated, diseased or damaged tissues. In this context, principles of regenerative science are increasingly integrated in rehabilitation practices as illustrated in the present Supplement. Encompassing a growing multidisciplinary domain, the emergent era of “regenerative rehabilitation” brings radical innovations at the forefront of healthcare blueprints. PMID:25310603

Three-dimensional bioprinting in tissue engineering and regenerative medicine.

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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.

Regenerative Medicine for Epilepsy: From Basic Research to Clinical Application

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Takao Yasuhara

2013-11-01

Full Text Available 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.

Regenerative medicine using dental pulp stem cells for liver diseases.

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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.

Artificial intelligence: A joint narrative on potential use in pediatric stem and immune cell therapies and regenerative medicine.

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Sniecinski, Irena; Seghatchian, Jerard

2018-05-09

Artificial Intelligence (AI) reflects the intelligence exhibited by machines and software. It is a highly desirable academic field of many current fields of studies. Leading AI researchers describe the field as "the study and design of intelligent agents". McCarthy invented this term in 1955 and defined it as "the science and engineering of making intelligent machines". The central goals of AI research are reasoning, knowledge, planning, learning, natural language processing (communication), perception and the ability to move and manipulate objects. In fact the multidisplinary AI field is considered to be rather interdisciplinary covering numerous number of sciences and professions, including computer science, psychology, linguistics, philosophy and neurosciences. The field was founded on the claim that a central intellectual property of humans, intelligence-the sapience of Homo Sapiens "can be so precisely described that a machine can be made to simulate it". This raises philosophical issues about the nature of the mind and the ethics of creating artificial beings endowed with human-like intelligence. Artificial Intelligence has been the subject of tremendous optimism but has also suffered stunning setbacks. The goal of this narrative is to review the potential use of AI approaches and their integration into pediatric cellular therapies and regenerative medicine. Emphasis is placed on recognition and application of AI techniques in the development of predictive models for personalized treatments with engineered stem cells, immune cells and regenerated tissues in adults and children. These intelligent machines could dissect the whole genome and isolate the immune particularities of individual patient's disease in a matter of minutes and create the treatment that is customized to patient's genetic specificity and immune system capability. AI techniques could be used for optimization of clinical trials of innovative stem cell and gene therapies in pediatric patients

REGEN: Ancestral Genome Reconstruction for Bacteria

OpenAIRE

Yang, Kuan; Heath, Lenwood S.; Setubal, João C.

2012-01-01

Ancestral genome reconstruction can be understood as a phylogenetic study with more details than a traditional phylogenetic tree reconstruction. We present a new computational system called REGEN for ancestral bacterial genome reconstruction at both the gene and replicon levels. REGEN reconstructs gene content, contiguous gene runs, and replicon structure for each ancestral genome. Along each branch of the phylogenetic tree, REGEN infers evolutionary events, including gene creation and deleti...

Hyperbaric oxygen therapy in a true regenerative environment, the regenerating limb of the axolotl

DEFF Research Database (Denmark)

Hansen, Kasper; Lauridsen, Henrik; Pedersen, Michael

2012-01-01

vertebrates such as the urodele amphibians (salamanders and newts), are excellent animal models for regenerative studies. The iconic Mexican axolotl (Ambystoma mexicanum) is capable of regenerating whole limbs, tail, jaw, and many inner organs, by dedifferentiation of cells to form a blastema (collection...

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting.

Science.gov (United States)

Trindade, Fábio; Leite-Moreira, Adelino; Ferreira-Martins, João; Ferreira, Rita; Falcão-Pires, Inês; Vitorino, Rui

2017-02-01

Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice.

Science.gov (United States)

D Agostino, M C; Frairia, R; Romeo, P; Amelio, E; Berta, L; Bosco, V; Gigliotti, S; Guerra, C; Messina, S; Messuri, L; Moretti, B; Notarnicola, A; Maccagnano, G; Russo, S; Saggini, R; Vulpiani, M C; Buselli, P

2016-01-01

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.

State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews

Directory of Open Access Journals (Sweden)

Mariangela Peruzzi

2015-01-01

Full Text Available Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients. Twenty-two (54% reviews focused on acute myocardial infarction (AMI, 19 (46% on chronic ischemic heart disease (IHD or heart failure (HF, 29 (71% on bone marrow-derived stem-cells (BMSC, and 36 (88% to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11, effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%], and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]. No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P=0.008 and showed more pronounced effect estimates (P=0.002. Higher citations were associated with journal impact factor (P=0.007, corresponding author from North America/Europe (P=0.022, and inclusion of nonrandomized trials (P=0.046. Conclusions. Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.

Translating the Essence of Dance: Rendering Meaning in Artistic Inquiry of the Creative Arts Therapies

Science.gov (United States)

Manders, Elizabeth; Chilton, Gioia

2013-01-01

The authors used artistic inquiry to study intersubjectivity in a weekly, stimulated creative arts therapy studio experience for one year. They found that the conversion of meaning from the meta-verbal, imaginal, aesthetic language of dance and visual art into verbal and textual discourse required complex translational processes. Personal…

Summary of: Regenerative endodontics.

Science.gov (United States)

Clark, Stephen J

2014-03-01

Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

Science.gov (United States)

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

Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review.

Science.gov (United States)

Nguyen, Patricia K; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C

2016-11-01

Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist. To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them. Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included. One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.

Gingiva as a new and the most accessible source of mesenchymal stem cells from the oral cavity to be used in regenerative therapies

Directory of Open Access Journals (Sweden)

Bartłomiej Górski

2016-08-01

Full Text Available Since the discovery of bone marrow mesenchymal stem cells (BMMSCs, many researchers have focused their attention on new sources of mesenchymal stem cells (MSCs. Consequently, MSCs that display self-renewal capacity, multidifferentiation potential and immunomodulatory properties have been isolated from human oral tissues, including tooth, periodontal ligament, and gingiva. Oral MSCs involve dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, periodontal ligament stem cells (PDLSCs, dental follicle stem cells (DFCs, stem cells from apical papilla (SCAP and gingival stem cells (GMSCs. Current research on oral stem cells is expanding at an unprecedented rate. That being the case, a plethora of in vitro differentiation assays, immunodeficient animal transplantations and preclinical trials have demonstrated that these cells exhibit strong potential for both regenerative dentistry and medicine. Oral MSCs have proved their capability to repair cornea, dental pulp, periodontal, bone, cartilage, tendon, neural, muscle and endothelial tissues without neoplasm formation as well as to treat inflammatory diseases and immune disorders. This article describes the current understanding of oral MSCs and their prospective applications in cell-based therapy, tissue engineering and regenerative medicine. Special attention is placed on GMSCs as they are easily accessible and may be obtained in a convenient and minimally invasive way.

Phenotypic characterization of the bone marrow stem cells used in regenerative cellular therapy

International Nuclear Information System (INIS)

Macias Abraham, Consuelo; Valle Perez, Lazaro O del; Baganet Cobas, Aymara

2011-01-01

Regenerative medicine is a novel therapeutic method with broad potential for the treatment of various illnesses, based on the use of bone marrow (BM) stem cells, whose phenotypic characterization is limited. The paper deals with the expression of different cell membrane markers in mononuclear BM cells from 14 patients who underwent autologous cell therapy, obtained by medullary puncture and mobilization to peripheral blood, with the purpose of characterizing the different types of cells present in that heterogeneous cellular population and identifying the adhesion molecules involved in their adhesion. A greater presence was observed of adherent stem cells from the marrow stroma in mononuclear cells obtained directly from the BM; a larger population of CD90 +c ells in mononuclear cells from CD34 -/ CD45 -p eripheral blood with a high expression of molecules CD44 and CD62L, which suggests a greater presence of mesenchymal stem cells (MSC) in mobilized cells from the marrow stroma. The higher levels of CD34 +c ells in peripheral blood stem cells with a low expression of molecules CD117 -a nd DR -s uggests the presence of hematopoietic stem cells, hemangioblasts and progenitor endothelial cells mobilized to peripheral circulation. It was found that mononuclear cells from both the BM and peripheral blood show a high presence of stem cells with expression of adhesion molecule CD44 (MMC marker), probably involved in their migration, settling and differentiation

Imperative role of dental pulp stem cells in regenerative therapies: A systematic review

Directory of Open Access Journals (Sweden)

Ramchandra Kabir

2014-01-01

Full Text Available Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase using keywords like "dental pulp stem cells", "regeneration", "medical applications", "tissue engineering". DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective.

Imperative role of dental pulp stem cells in regenerative therapies: a systematic review.

Science.gov (United States)

Kabir, Ramchandra; Gupta, Manish; Aggarwal, Avanti; Sharma, Deepak; Sarin, Anurag; Kola, Mohammed Zaheer

2014-01-01

Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like "dental pulp stem cells", "regeneration", "medical applications", "tissue engineering". DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective.

Gene and Cell Therapy for β-Thalassemia and Sickle Cell Disease with Induced Pluripotent Stem Cells (iPSCs): The Next Frontier.

Science.gov (United States)

Papapetrou, Eirini P

2017-01-01

In recent years, breakthroughs in human pluripotent stem cell (hPSC) research, namely cellular reprogramming and the emergence of sophisticated genetic engineering technologies, have opened new frontiers for cell and gene therapy. The prospect of using hPSCs, either autologous or histocompatible, as targets of genetic modification and their differentiated progeny as cell products for transplantation, presents a new paradigm of regenerative medicine of potential tremendous value for the treatment of blood disorders, including beta-thalassemia (BT) and sickle cell disease (SCD). Despite advances at a remarkable pace and great promise, many roadblocks remain before clinical translation can be realistically considered. Here we discuss the theoretical advantages of cell therapies utilizing hPSC derivatives, recent proof-of-principle studies and the main challenges towards realizing the potential of hPSC therapies in the clinic.

A review of the regenerative endodontic treatment procedure

Directory of Open Access Journals (Sweden)

Bin-Na Lee,

2015-08-01

Full Text Available Traditionally, apexification has been used to treat immature permanent teeth that have lost pulp vitality. This technique promotes the formation of an apical barrier to close the open apex so that the filling materials can be confined to the root canal. Because tissue regeneration cannot be achieved with apexification, a new technique called regenerative endodontic treatment was presented recently to treat immature permanent teeth. Regenerative endodontic treatment is a treatment procedure designed to replace damaged pulp tissue with viable tissue which restores the normal function of the pulp-dentin structure. After regenerative endodontic treatment, continued root development and hard tissue deposition on the dentinal wall can occur under ideal circumstances. However, it is difficult to predict the result of regenerative endodontic treatment. Therefore, the purpose of this study was to summarize multiple factors effects on the result of regenerative endodontic treatment in order to achieve more predictable results. In this study, we investigated the features of regenerative endodontic treatment in comparison with those of other pulp treatment procedures and analyzed the factors that have an effect on regenerative endodontic treatment.

[Evidence-based therapy for cartilage lesions in the knee - regenerative treatment options].

Science.gov (United States)

Proffen, B; von Keudell, A; Vavken, P

2012-06-01

The treatment of cartilage defects has seen a shift from replacement to regeneration in the last few years. The rationale behind this development is the improvement in the quality-of-care for the growing segment of young patients who are prone to arthroplasty complications because of their specific characteristics - young age, high level of activity, high demand for functionality. These days, two of the most popular regenerative treatments are microfracture and autologous chondrocyte implantation (ACI). Although these new options show promising results, no final algorithm for the treatment of cartilage lesions has been established as yet. The objective of this review is to describe and compare these two treatment options and to present an evidence-based treatment algorithm for focal cartilage defects. Microfracture is a cost-effective, arthroscopic one-stage procedure, in which by drilling of the subchondral plate, mesenchymal stem cells from the bone marrow migrate into the defect and rebuild the cartilage. ACI is a two-stage procedure in which first chondrocytes are harvested, expanded in cell culture and in a second open procedure reimplanted into the cartilage defect. Microfracture is usually used for focal cartilage defects osteophyte, and for the ACI patient, periosteal hypertrophy and the need for two procedures in ACI. Only a few studies provide detailed and evidence-based information on a comparative assessment. These studies, however, are showing widely similar clinical outcomes but better histological results for ACI, which are likely to translate into better long-term outcomes. Although evidence-based studies comparing microfracture and ACI have not found significant differences in the clinical outcome, the literature does show that choosing the treatment based on the size and characteristics of the osteochondral lesion might be beneficial. The American Association of Orthopedic Surgeons suggest that contained lesions < 4 cm2 should be treated by

Regenerative-filter-incinerator device

Energy Technology Data Exchange (ETDEWEB)

Rosebrock, T.L.

1977-10-18

A regenerative-filter-incinerator device, for use in the exhaust system of a diesel engine, includes a drum-like regenerative-heat exchanger-filter assembly rotatably mounted within a housing that is adapted to be installed directly in the exhaust gas stream discharged from a diesel engine as close to the engine as possible. The regenerative-heat exchanger-filter assembly provides an inner chamber which serves as a reaction chamber for the secondary combustion of exhaust gases including particulates discharged from the engine. The regenerative-heat exchanger-filter assembly includes separately rotatable heat exchange-filter elements pervious to radial flow of fluid therethrough and adapted to filter out particulates from the exhaust gases and to carry them into the reaction chamber. During engine operation, the reaction chamber is provided with a quantity of heat, as necessary, to effect secondary combustion of the exhaust gases and particulates by means of an auxiliary heat source and the heat generated within the reaction chamber is stored in the individual heat exchange-filter elements during the discharge of exhaust gases therethrough from the reaction chamber and this heat is then transferred to the inflowing volume of the exhaust gases so that, in effect, exhaust gas is discharged from the device at substantially the same temperature as it was during its inlet into the device from the engine.

Regenerative braking system of PM synchronous motor

Science.gov (United States)

Gao, Qian; Lv, Chengxing; Zhao, Na; Zang, Hechao; Jiang, Huilue; Zhang, Zhaowen; Zhang, Fengli

2018-04-01

Permanent-magnet synchronous motor is widely adopted in many fields with the advantage of a high efficiency and a high torque density. Regenerative Braking Systems (RBS) provide an efficient method to assist PMSM system achieve better fuel economy and lowering exhaust emissions. This paper describes the design and testing of the regenerative braking systems of PMSM. The mode of PWM duty has been adjusted to control regenerative braking of PMSM using energy controller for the port-controlled Hamiltonian model. The simulation analysis indicates that a smooth control could be realized and the highest efficiency and the smallest current ripple could be achieved by Regenerative Braking Systems.

Template mediated protein self-assembly as a valuable tool in regenerative therapy.

Science.gov (United States)

Kundu, B; Eltohamy, M; Yadavalli, V K; Reis, R L; Kim, H W

2018-04-11

The assembly of natural proteinaceous biopolymers into macro-scale architectures is of great importance in synthetic biology, soft-material science and regenerative therapy. The self-assembly of protein tends to be limited due to anisotropic interactions among protein molecules, poor solubility and stability. Here, we introduce a unique platform to self-immobilize diverse proteins (fibrous and globular, positively and negatively charged, low and high molecular weight) using silicon surfaces with pendant -NH 2 groups via a facile one step diffusion limited aggregation (DLA) method. All the experimental proteins (type I collagen, bovine serum albumin and cytochrome C) self-assemble into seaweed-like branched dendritic architectures via classical DLA in the absence of any electrolytes. The notable differences in branching architectures are due to dissimilarities in protein colloidal sub-units, which is typical for each protein type, along with the heterogeneous distribution of surface -NH 2 groups. Fractal analysis of assembled structures is used to explain the underlying route of fractal deposition; which concludes how proteins with different functionality can yield similar assembly. Further, the nano-micro-structured surfaces can be used to provide functional topographical cues to study cellular responses, as demonstrated using rat bone marrow stem cells. The results indicate that the immobilization of proteins via DLA does not affect functionality, instead serving as topographical cues to guide cell morphology. This indicates a promising design strategy at the tissue-material interface and is anticipated to guide future surface modifications. A cost-effective standard templating strategy is therefore proposed for fundamental and applied particle aggregation studies, which can be used at multiple length scales for biomaterial design and surface reformation.

Current overview on challenges in regenerative endodontics

Science.gov (United States)

Bansal, Ramta; Jain, Aditya; Mittal, Sunandan

2015-01-01

Introduction: Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment. Aim: The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice. Materials and Methods: A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were “regenerative endodontics,” “dental stem cells,” “growth factor regeneration,” “scaffolds,” and “challenges in regeneration.” This review article screened about 150 articles and then the relevant information was compiled. Results: Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes. Conclusion: Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth. PMID:25657518

Scanning the horizon for high value-add manufacturing science: Accelerating manufacturing readiness for the next generation of disruptive, high-value curative cell therapeutics.

Science.gov (United States)

Hourd, Paul; Williams, David J

2018-05-01

Since the regenerative medicine sector entered the second phase of its development (RegenMed 2.0) more than a decade ago, there is increasing recognition that current technology innovation trajectories will drive the next translational phase toward the production of disruptive, high-value curative cell and gene-based regenerative medicines. To identify the manufacturing science problems that must be addressed to permit translation of these next generation therapeutics. In this short report, a long lens look within the pluripotent stem cell therapeutic space, both embryonic and induced, is used to gain early insights on where critical technology and manufacturing challenges may emerge. This report offers a future perspective on the development and innovation that will be needed within manufacturing science to add value in the production and commercialization of the next generation of advanced cell therapies and precision medicines. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Aging and Adipose Tissue: Potential Interventions for Diabetes and Regenerative Medicine

Science.gov (United States)

Palmer, Allyson K.; Kirkland, James L.

2016-01-01

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. PMID:26924669

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance.

Science.gov (United States)

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. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Cell and biomolecule delivery for regenerative medicine

Science.gov (United States)

Smith, Ian O; Ma, Peter X

2010-01-01

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. PMID:27877317

Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advances.

Science.gov (United States)

Kawase, Tomoyuki

2015-05-01

Over the past decade, platelet-rich plasma (PRP), a platelet-concentrated plasma fraction, has been widely investigated and applied to regenerative medicine. The clinical utility of PRP is supported by evidence that PRP contains high concentrations of platelet-related growth factors and normal concentrations of plasma-derived fibrinogen, both of which contribute synergistically to the regenerative process. Additionally, its superior cost-efficacy versus conventional therapies is attractive to many clinicians. However, current disadvantages of PRP include a relatively complicated preparation procedure and variable operator-dependent efficacy. An additional disadvantage is the use of bovine thrombin, an animal-derived biological, as a coagulant. Many of these disadvantages are overcome by recent advances in preparation procedures and devices; for example, Joseph Choukroun simplified the platelet-rich fibrin preparation procedure and improved handling efficiency without the aid of animal-derived factors. With advancements in cell processing technology, there has been a general shift in cell therapy from autologous to allogeneic treatment; however, autologous PRP therapy will not easily be replaced by allogeneic treatment in the near future. Therefore, to provide more predictable regenerative therapy outcomes using autologous PRP, further investigations should address developing a standardized procedure for PRP preparation to augment its efficacy and potency, independent of donor variability. We would then propose that operators and clinicians prepare PRP according to the standardized protocol and to carefully evaluate the clinical scenario (i.e., recipient factors comprising skeletal defects) to determine which factor(s) should be added to PRP preparations. This careful approach will lead to improved clinical outcomes for patients.

Comparative energy analysis on a new regenerative Brayton cycle

International Nuclear Information System (INIS)

Goodarzi, M.

2016-01-01

Highlights: • New regenerative Brayton cycle has been introduced. • New cycle has higher thermal efficiency and lower exhausted heat per output power. • Regenerator may remain useful in the new cycle even at high pressure ratio. • New regenerative Brayton cycle is suggested for low pressure ratio operations. - Abstract: Gas turbines are frequently used for power generation. Brayton cycle is the basis for gas turbine operation and developing the alternative cycles. Regenerative Brayton cycle is a developed cycle for basic Brayton cycle with higher thermal efficiency at low to moderate pressure ratios. A new regenerative Brayton cycle has been introduced in the present study. Energy analysis has been conducted on ideal cycles to compare them from the first law of thermodynamics viewpoint. Comparative analyses showed that the new regenerative Brayton cycle has higher thermal efficiency than the original one at the same pressure ratio, and also lower heat absorption and exhausted heat per unite output power. Computed results show that new cycle improves thermal efficiency from 12% to 26% relative to the original regenerative Brayton cycle in the range of studied pressure ratios. Contrary to the original regenerative Brayton cycle, regenerator remains useful in the new regenerative Brayton cycle even at higher pressure ratio.

Translational Research for Occupational Therapy: Using SPRE in Hippotherapy for Children with Developmental Disabilities.

Science.gov (United States)

Weissman-Miller, Deborah; Miller, Rosalie J; Shotwell, Mary P

2017-01-01

Translational research is redefined in this paper using a combination of methods in statistics and data science to enhance the understanding of outcomes and practice in occupational therapy. These new methods are applied, using larger data and smaller single-subject data, to a study in hippotherapy for children with developmental disabilities (DD). The Centers for Disease Control and Prevention estimates DD affects nearly 10 million children, aged 2-19, where diagnoses may be comorbid. Hippotherapy is defined here as a treatment strategy in occupational therapy using equine movement to achieve functional outcomes. Semiparametric ratio estimator (SPRE), a single-subject statistical and small data science model, is used to derive a "change point" indicating where the participant adapts to treatment, from which predictions are made. Data analyzed here is from an institutional review board approved pilot study using the Hippotherapy Evaluation and Assessment Tool measure, where outcomes are given separately for each of four measured domains and the total scores of each participant. Analysis with SPRE, using statistical methods to predict a "change point" and data science graphical interpretations of data, shows the translational comparisons between results from larger mean values and the very different results from smaller values for each HEAT domain in terms of relationships and statistical probabilities.

Translational Research for Occupational Therapy: Using SPRE in Hippotherapy for Children with Developmental Disabilities

Science.gov (United States)

Miller, Rosalie J.; Shotwell, Mary P.

2017-01-01

Translational research is redefined in this paper using a combination of methods in statistics and data science to enhance the understanding of outcomes and practice in occupational therapy. These new methods are applied, using larger data and smaller single-subject data, to a study in hippotherapy for children with developmental disabilities (DD). The Centers for Disease Control and Prevention estimates DD affects nearly 10 million children, aged 2–19, where diagnoses may be comorbid. Hippotherapy is defined here as a treatment strategy in occupational therapy using equine movement to achieve functional outcomes. Semiparametric ratio estimator (SPRE), a single-subject statistical and small data science model, is used to derive a “change point” indicating where the participant adapts to treatment, from which predictions are made. Data analyzed here is from an institutional review board approved pilot study using the Hippotherapy Evaluation and Assessment Tool measure, where outcomes are given separately for each of four measured domains and the total scores of each participant. Analysis with SPRE, using statistical methods to predict a “change point” and data science graphical interpretations of data, shows the translational comparisons between results from larger mean values and the very different results from smaller values for each HEAT domain in terms of relationships and statistical probabilities. PMID:29097962

Translational Research for Occupational Therapy: Using SPRE in Hippotherapy for Children with Developmental Disabilities

Directory of Open Access Journals (Sweden)

Deborah Weissman-Miller

2017-01-01

Full Text Available Translational research is redefined in this paper using a combination of methods in statistics and data science to enhance the understanding of outcomes and practice in occupational therapy. These new methods are applied, using larger data and smaller single-subject data, to a study in hippotherapy for children with developmental disabilities (DD. The Centers for Disease Control and Prevention estimates DD affects nearly 10 million children, aged 2–19, where diagnoses may be comorbid. Hippotherapy is defined here as a treatment strategy in occupational therapy using equine movement to achieve functional outcomes. Semiparametric ratio estimator (SPRE, a single-subject statistical and small data science model, is used to derive a “change point” indicating where the participant adapts to treatment, from which predictions are made. Data analyzed here is from an institutional review board approved pilot study using the Hippotherapy Evaluation and Assessment Tool measure, where outcomes are given separately for each of four measured domains and the total scores of each participant. Analysis with SPRE, using statistical methods to predict a “change point” and data science graphical interpretations of data, shows the translational comparisons between results from larger mean values and the very different results from smaller values for each HEAT domain in terms of relationships and statistical probabilities.

Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

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Ting Gong

2016-01-01

Full Text Available Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration.

Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

Science.gov (United States)

Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

2016-01-01

Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

Microscale Regenerative Heat Exchanger

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Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

2006-01-01

The device described herein is designed primarily for use as a regenerative heat exchanger in a miniature Stirling engine or Stirling-cycle heat pump. A regenerative heat exchanger (sometimes called, simply, a "regenerator" in the Stirling-engine art) is basically a thermal capacitor: Its role in the Stirling cycle is to alternately accept heat from, then deliver heat to, an oscillating flow of a working fluid between compression and expansion volumes, without introducing an excessive pressure drop. These volumes are at different temperatures, and conduction of heat between these volumes is undesirable because it reduces the energy-conversion efficiency of the Stirling cycle.

Regenerative Braking System for Series Hybrid Electric City Bus

OpenAIRE

Zhang, Junzhi; Lu, Xin; Xue, Junliang; Li, Bos

2008-01-01

Regenerative Braking Systems (RBS) provide an efficient method to assist hybrid electric buses achieve better fuel economy while lowering exhaust emissions. This paper describes the design and testing of three regenerative braking systems, one of which is a series regenerative braking system and two of which are parallel regenerative braking systems. The existing friction based Adjustable Braking System (ABS) on the bus is integrated with each of the new braking systems in order to ensure bus...

Honey: an effective regenerative medicine product in wound management.

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Martinotti, Simona; Bucekova, Marcela; Majtan, Juraj; Ranzato, Elia

2018-05-10

Honey has successfully been used in treatment of a broad spectrum of injuries including burns and non-healing wounds. It acts as antibacterial and anti-biofilm agent with anti/pro-inflammatory properties. However, besides these traditional properties, recent evidence suggests that honey is also an immunomodulator in wound healing and contains several bee and plant-derived components that may speed up the wound healing and tissue regeneration process. Identifying their exact mechanism of action allows better understanding of honey healing properties and promotes its wider translation into clinical practice. This review will discuss the physiological basis for the use of honey in wound management, its current clinical uses, as well as the potential role of honey bioactive compounds in dermal regenerative medicine and tissue re-modelling. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Upcycling umbilical cords: bridging regenerative medicine with neonatology.

Science.gov (United States)

Moreira, Alvaro; Alayli, Yasmeen; Balgi, Saloni; Winter, Caitlyn; Kahlenberg, Samuel; Mustafa, Shamimunisa; Hornsby, Peter

2017-11-27

Preterm birth is a major health concern that affects 10% of all worldwide deliveries. Many preterm infants are discharged from the hospital with morbidities that lead to an increased risk for neurodevelopmental impairment, recurrent hospitalizations, and life-long conditions. Unfortunately, the treatment of these conditions is palliative rather than curative, which calls for novel and innovative strategies. Progress in regenerative medicine has offered therapeutic options for many of these conditions. Specifically, human umbilical cord mesenchymal stem cells (MSCs) and cord blood (UCB) cells have shown promise in treating adult-onset diseases. Unlike bone-marrow and embryonic derived stem cells, umbilical cord-derived cells are easily and humanely obtained, have low immunogenicity, and offer the potential of autologous therapy. While there are several studies to uphold the efficacy of umbilical cord MSCs in adult therapies, there remains an unmet need for the investigation of its use in treating neonates. The purpose of this review is to provide a summary of current information on the potential therapeutic benefits and clinical applicability of umbilical cord MSCs and UCB cells. Promising preclinical studies have now led to a research movement that is focusing on cell-based therapies for preterm infants.

Cryopreserved Dental Pulp Tissues of Exfoliated Deciduous Teeth Is a Feasible Stem Cell Resource for Regenerative Medicine

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Yamaza, Haruyoshi; Akiyama, Kentaro; Hoshino, Yoshihiro; Song, Guangtai; Kukita, Toshio; Nonaka, Kazuaki; Shi, Songtao; Yamaza, Takayoshi

2012-01-01

Human exfoliated deciduous teeth have been considered to be a promising source for regenerative therapy because they contain unique postnatal stem cells from human exfoliated deciduous teeth (SHED) with self-renewal capacity, multipotency and immunomodulatory function. However preservation technique of deciduous teeth has not been developed. This study aimed to evaluate that cryopreserved dental pulp tissues of human exfoliated deciduous teeth is a retrievable and practical SHED source for cell-based therapy. SHED isolated from the cryopreserved deciduous pulp tissues for over 2 years (25–30 months) (SHED-Cryo) owned similar stem cell properties including clonogenicity, self-renew, stem cell marker expression, multipotency, in vivo tissue regenerative capacity and in vitro immunomodulatory function to SHED isolated from the fresh tissues (SHED-Fresh). To examine the therapeutic efficacy of SHED-Cryo on immune diseases, SHED-Cryo were intravenously transplanted into systemic lupus erythematosus (SLE) model MRL/lpr mice. Systemic SHED-Cryo-transplantation improved SLE-like disorders including short lifespan, elevated autoantibody levels and nephritis-like renal dysfunction. SHED-Cryo amended increased interleukin 17-secreting helper T cells in MRL/lpr mice systemically and locally. SHED-Cryo-transplantation was also able to recover osteoporosis bone reduction in long bones of MRL/lpr mice. Furthermore, SHED-Cryo-mediated tissue engineering induced bone regeneration in critical calvarial bone-defect sites of immunocompromised mice. The therapeutic efficacy of SHED-Cryo transplantation on immune and skeletal disorders was similar to that of SHED-Fresh. These data suggest that cryopreservation of dental pulp tissues of deciduous teeth provide a suitable and desirable approach for stem cell-based immune therapy and tissue engineering in regenerative medicine. PMID:23251621

An overview of periodontal regenerative procedures for the general dental practitioner

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M. Siaili

2018-01-01

Full Text Available The complete regeneration of the periodontal tissues following periodontal disease remains an unmet challenge, and has presented clinicians with a remarkably difficult clinical challenge to solve given the extensive research in this area and our current understanding of the biology of the periodontal tissues. In particular as clinicians we look for treatments that will improve the predictability of the procedure, improve the magnitude of the effect of treatment, and perhaps most importantly in the long term would extend the indications for treatment beyond the need for single enclosed bony defects to allow for suprabony regeneration, preferably with beneficial effects on the gingival soft tissues. A rapid development in both innovative methods and products for the correction of periodontal deficiencies have been reported during the last three decades. For example, guided tissue regeneration with or without the use of bone supplements has been a well-proven treatment modality for the reconstruction of bony defects prior to the tissue engineering era. Active biomaterials have been subsequently introduced to the periodontal community with supporting dental literature suggesting that certain factors should be taken into consideration when undertaking periodontal regenerative procedures. These factors as well as a number of other translational research issues will need to be addressed, and ultimately it is vital that we do not extrapolate results from pre-clinical and animal studies without conducting extensive randomized clinical trials to substantiate outcomes from these procedures. Whatever the outcomes, the pursuit of regeneration of the periodontal tissues remains a goal worth pursuing for our patients. The aim of the review, therefore is to update clinicians on the recent advances in both materials and techniques in periodontal regenerative procedures and to highlight the importance of both patient factors and the technical aspects of

VEGFR-2 expression in HCC, dysplastic and regenerative liver nodules, and correlation with pre-biopsy Dynamic Contrast Enhanced CT

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Thaiss, W.M., E-mail: wolfgang.thaiss@med.uni-tuebingen.de [Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen (Germany); Kaufmann, S., E-mail: sascha.kaufmann@med.uni-tuebingen.de [Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen (Germany); Kloth, C., E-mail: christopher.kloth@med.uni-tuebingen.de [Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen (Germany); Nikolaou, K., E-mail: konstantin.nikolaou@med.uni-tuebingen.de [Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen (Germany); Bösmüller, H., E-mail: hans.boesmueller@med.uni-tuebingen.de [Eberhard Karls University, Department of Pathology, Liebermeisterstraße 8, D-72076 Tuebingen (Germany); Horger, M., E-mail: Marius.Horger@med.uni-tuebingen.de [Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen (Germany)

2016-11-15

Highlights: • VEGFR-2-expression levels vary between HCC, dysplastic and regenerative liver nodules. • Perfusion parameters vary between these groups in blood flow, blood volume and HPI. • Strong correlations were observed between perfusion parameters and VEGFR-2-expression. • The results might influence diagnosis and therapy of anti-vascular therapeutic regimes. - Abstract: Purpose: To evaluate whether VEGFR-2-expression in hepatocellular carcinoma (HCC), dysplastic (DLN) and regenerative liver nodules (RLN) correlates with pre-histology, in vivo Dynamic Contrast Enhanced-Computed Tomography (DCE-CT) data as VEGFR-2-expression affects prognosis and therapeutic options. Materials and methods: 34 patients (63.6 ± 8.9 years, 7 females) underwent liver biopsy or surgery due to suspected HCC or dysplastic nodules after DCE-CT between 2009 and 2015 with no previous chemo- or interventional therapy. Immunohistochemistry staining for VEGFR-2 was performed using Immunoreactive-Remmele-Stegner-Score (IRS) for quantification. A 128-row CT-scanner was used for DCE-CT with assessment of perfusion parameters blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal venous perfusion (PVP), and hepatic perfusion index (HPI). Results: Histology confirmed HCC (n = 10), DLN (n = 7) and RLN (n = 34). Mean IRS for VEGFR-2 in HCCs was 9.1 ± 3.0, 7.3 ± 1.6 for DLN and 5.2 ± 2.8 for RLN (p = 0.0004 for HCC vs. RLN). Perfusion values varied significantly between all three groups for BF and HPI (p < 0.001 and p < 0.0001) and for BV in HCC vs. RLN (p < 0.0001) and DLN vs. RLN (p = 0.0019). Strong correlations between VEGFR-2-IRS and perfusion parameters were observed for BF in HCC (r = 0.88, p < 0.01) and HPI in HCC and DLN (r = 0.85, p < 0.04; r = 0.9, p < 0.01). Conclusion: Immunostaining revealed different VEGFR-2-expression levels in HCC, dysplastic and regenerative liver nodules. Perfusion markers blood flow, blood volume and hepatic perfusion index

Design of An Energy Efficient Hydraulic Regenerative circuit

Science.gov (United States)

Ramesh, S.; Ashok, S. Denis; Nagaraj, Shanmukha; Adithyakumar, C. R.; Reddy, M. Lohith Kumar; Naulakha, Niranjan Kumar

2018-02-01

Increasing cost and power demand, leads to evaluation of new method to increase through productivity and help to solve the power demands. Many researchers have break through to increase the efficiency of a hydraulic power pack, one of the promising methods is the concept of regenerative. The objective of this research work is to increase the efficiency of a hydraulic circuit by introducing a concept of regenerative circuit. A Regenerative circuit is a system that is used to speed up the extension stroke of the double acting single rod hydraulic cylinder. The output is connected to the input in the directional control value. By this concept, increase in velocity of the piston and decrease the cycle time. For the research, a basic hydraulic circuit and a regenerative circuit are designated and compared both with their results. The analysis was based on their time taken for extension and retraction of the piston. From the detailed analysis of both the hydraulic circuits, it is found that the efficiency by introducing hydraulic regenerative circuit increased by is 5.3%. The obtained results conclude that, implementing hydraulic regenerative circuit in a hydraulic power pack decreases power consumption, reduces cycle time and increases productivity in a longer run.

A One Health overview, facilitating advances in comparative medicine and translational research.

Science.gov (United States)

Stroud, Cheryl; Dmitriev, Igor; Kashentseva, Elena; Bryan, Jeffrey N; Curiel, David T; Rindt, Hans; Reinero, Carol; Henry, Carolyn J; Bergman, Philip J; Mason, Nicola J; Gnanandarajah, Josephine S; Engiles, Julie B; Gray, Falon; Laughlin, Danielle; Gaurnier-Hausser, Anita; Wallecha, Anu; Huebner, Margie; Paterson, Yvonne; O'Connor, Daniel; Treml, Laura S; Stannard, James P; Cook, James L; Jacobs, Marc; Wyckoff, Gerald J; Likins, Lee; Sabbagh, Ubadah; Skaff, Andrew; Guloy, Amado S; Hays, Harlen D; LeBlanc, Amy K; Coates, Joan R; Katz, Martin L; Lyons, Leslie A; Johnson, Gayle C; Johnson, Gary S; O'Brien, Dennis P; Duan, Dongsheng; Calvet, James P; Gandolfi, Barbara; Baron, David A; Weiss, Mark L; Webster, Debra A; Karanu, Francis N; Robb, Edward J; Harman, Robert J

2016-08-01

kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman.

Tissue-engineering-based Strategies for Regenerative Endodontics

Science.gov (United States)

Albuquerque, M.T.P.; Valera, M.C.; Nakashima, M.; Nör, J.E.; Bottino, M.C.

2014-01-01

Stemming from in vitro and in vivo pre-clinical and human models, tissue-engineering-based strategies continue to demonstrate great potential for the regeneration of the pulp-dentin complex, particularly in necrotic, immature permanent teeth. Nanofibrous scaffolds, which closely resemble the native extracellular matrix, have been successfully synthesized by various techniques, including but not limited to electrospinning. A common goal in scaffold synthesis has been the notion of promoting cell guidance through the careful design and use of a collection of biochemical and physical cues capable of governing and stimulating specific events at the cellular and tissue levels. The latest advances in processing technologies allow for the fabrication of scaffolds where selected bioactive molecules can be delivered locally, thus increasing the possibilities for clinical success. Though electrospun scaffolds have not yet been tested in vivo in either human or animal pulpless models in immature permanent teeth, recent studies have highlighted their regenerative potential both from an in vitro and in vivo (i.e., subcutaneous model) standpoint. Possible applications for these bioactive scaffolds continue to evolve, with significant prospects related to the regeneration of both dentin and pulp tissue and, more recently, to root canal disinfection. Nonetheless, no single implantable scaffold can consistently guide the coordinated growth and development of the multiple tissue types involved in the functional regeneration of the pulp-dentin complex. The purpose of this review is to provide a comprehensive perspective on the latest discoveries related to the use of scaffolds and/or stem cells in regenerative endodontics. The authors focused this review on bioactive nanofibrous scaffolds, injectable scaffolds and stem cells, and pre-clinical findings using stem-cell-based strategies. These topics are discussed in detail in an attempt to provide future direction and to shed light on

Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

Directory of Open Access Journals (Sweden)

Coventry BJ

2012-05-01

therapy. This aspect has been somewhat obscured and has been "lost in translation" to date.Keywords: chemotherapy, immunotherapy, immune response, common pathways, translational research, oscillation, regulatory T-cells, immune modulation, complete responses

A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy

Directory of Open Access Journals (Sweden)

Miki Ando

2015-10-01

Full Text Available The discovery of induced pluripotent stem cells (iPSCs has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation. To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9 into iPSCs. Activation of iC9 with a specific chemical inducer of dimerization (CID initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs. We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killing activity. iC9-expressing rejCTLs exert antitumor effects in vivo. The system efficiently and safely induces apoptosis in these rejCTLs. These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy.

Regenerative medicine and responsible research and innovation: proposals for a responsible acceleration to the clinic.

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Webster, Andrew

2017-10-01

This paper asks how regenerative medicine can be examined through the 'responsible research and innovation' (RRI) approach which has been developed over the past decade. It describes the drivers to the development of RRI, and then argues for the need to understand innovation itself through drawing on social science analysis rooted in science and technology studies. The paper then identifies a number of highly specific challenges faced by the regenerative medicine field and the implications these have for value creation. It offers a number of examples of how a combined RRI/science and technology studies perspective can identify priority areas for policy and concludes by arguing for a 'responsible acceleration', more likely to foster readiness at a time when much of the policy domain is pushing for ever-rapid access to cell therapies.

Aarhus Regenerative Orthopaedics Symposium (AROS)

DEFF Research Database (Denmark)

Foldager, Casper B.; Bendtsen, Michael; Berg, Lise C.

2016-01-01

to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal......, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem. © 2017 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation....

Clinical translation of photobiomodulation therapy using evidences from precision molecular pathway analyses (Conference Presentation)

Science.gov (United States)

Arany, Praveen

2017-02-01

Can `light' be a Drug? To satisfy this definition as a pharmaceutical agent, light must be absorbed and change bodily function. Much evidence from our understanding of our visual cycle and Vitamin D metabolism have all noted this phenomenon. Advances in optophotonic technologies along with a better understanding of light-tissue interactions, especially in in vivo optical imaging and optogenetics, are spearheading the popularity of biophotonics in biology and medicine. The use of lasers and light devices at high doses in dermatology, ophthalmology, oncology and dentistry are now considered mainstream for certain clinical applications such as surgery, skin rejuvenation, ocular and soft tissue recontouring, anti-tumor and anti-microbial photodynamic therapy. In contrast, therapeutic use of low dose biophotonics devices is called Low Level Light / Laser Therapy (LLLT), now termed Photobiomodulation (PBM) Therapy. This therapy is defined as a non-thermal use of non-ionizing forms of electromagnetic radiation to alleviate pain, inflammation, modulating the immune responses and promoting wound healing and tissue regeneration. Surprisingly, despite vast volumes of scientific literature from both clinical and laboratory studies noting the phenomenological evidences for this innovative therapy, limited mechanistic insights have prevented the development of rigorous, reproducible clinical protocols. This presentation will outline our current efforts at ongoing efforts in our group to assess molecular pathways and precisely define clinical treatment variables to enable clinical translation with PBM therapies.

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

Science.gov (United States)

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. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

A survey of dental residents' expectations for regenerative endodontics.

Science.gov (United States)

Manguno, Christine; Murray, Peter E; Howard, Cameron; Madras, Jonathan; Mangan, Stephen; Namerow, Kenneth N

2012-02-01

The objective was to survey a group of dental residents regarding their expectations for using regenerative endodontic procedures as part of future dental treatments. After institutional review board approval, the opinions of 32 dentists who were having postgraduate residency training to become specialists in a dental school were surveyed. The survey had 40 questions about professional status, ethical beliefs, judgment, and clinical practice. It was found that 83.9% of dentists had no continuing education or training in stem cells or regenerative endodontic procedures. Results showed that 96.8% of dentists are willing to receive training to be able to provide regenerative endodontic procedures for their patients. Of the total group, 49.1% of dentists already use membranes, scaffolds, or bioactive materials to provide dental treatment. It was determined that 47.3% of dentists agree that the costs of regenerative procedures should be comparable with current treatments. It was also found that 55.1% of dentists were unsure whether regenerative procedures would be successful. Dentists are supportive of using regenerative endodontic procedures in their dental practice, and they are willing to undergo extra training and to buy new technology to provide new procedures. Nevertheless, dentists also need more evidence for the effectiveness and safety of regenerative treatments before they will be recommended for most patients. Copyright © 2012. Published by Elsevier Inc.

Cell therapy for spinal cord injury informed by electromagnetic waves.

Science.gov (United States)

Finnegan, Jack; Ye, Hui

2016-10-01

Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

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

Directory of Open Access Journals (Sweden)

Zheng Chen

2015-06-01

Full Text Available 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.

Translational and regulatory challenges for exon skipping therapies.

Science.gov (United States)

Aartsma-Rus, Annemieke; Ferlini, Alessandra; Goemans, Nathalie; Pasmooij, Anna M G; Wells, Dominic J; Bushby, Katerine; Vroom, Elizabeth; Balabanov, Pavel

2014-10-01

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.

How Regenerative Medicine Stakeholders Adapt to Ever-Changing Technology and Regulatory Challenges? Snapshots from the World TERMIS Industry Symposium (September 10, 2015, Boston).

Science.gov (United States)

Bayon, Yves; Van Dyke, Mark; Buelher, Robert; Tubo, Ross; Bertram, Tim; Malfroy-Camine, Bernard; Rathman, Michelle; Ronfard, Vincent

2017-04-01

Regenerative medicine (RM) is a fascinating area of research and innovation. The huge potential of the field has been fairly underexploited so far. Both TERMIS-AM and TERMIS-EU Industry Committees are committed to mentoring and training young entrepreneurs for more successful commercial translation of upstream research. With this objective in mind, the two entities jointly organized an industry symposium during the past TERMIS World Congress (Boston, September 8-11, 2015) and invited senior managers of the RM industry for lectures and panel discussions. One of the two sessions of the symposium-How to overcome obstacles encountered when bringing products to the commercial phase?-aimed to share the inside, real experiences of leaders from TEI Biosciences (an Integra Company), Vericel (formerly Aastrom; acquirer of Genzyme Regenerative Medicine assets), RegenMedTX (formerly Tengion), Mindset Rx, ViThera Pharmaceuticals, and L'Oreal Research & Innovation. The symposium provided practical recommendations for RM product development, for remaining critical and objective when reviewing progress, for keeping solutions simple, and for remaining relevant and persistent.

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

Science.gov (United States)

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.

Fetal skeletal muscle progenitors have regenerative capacity after intramuscular engraftment in dystrophin deficient mice.

Directory of Open Access Journals (Sweden)

Hiroshi Sakai

Full Text Available Muscle satellite cells (SCs are stem cells that reside in skeletal muscles and contribute to regeneration upon muscle injury. SCs arise from skeletal muscle progenitors expressing transcription factors Pax3 and/or Pax7 during embryogenesis in mice. However, it is unclear whether these fetal progenitors possess regenerative ability when transplanted in adult muscle. Here we address this question by investigating whether fetal skeletal muscle progenitors (FMPs isolated from Pax3(GFP/+ embryos have the capacity to regenerate muscle after engraftment into Dystrophin-deficient mice, a model of Duchenne muscular dystrophy. The capacity of FMPs to engraft and enter the myogenic program in regenerating muscle was compared with that of SCs derived from adult Pax3(GFP/+ mice. Transplanted FMPs contributed to the reconstitution of damaged myofibers in Dystrophin-deficient mice. However, despite FMPs and SCs having similar myogenic ability in culture, the regenerative ability of FMPs was less than that of SCs in vivo. FMPs that had activated MyoD engrafted more efficiently to regenerate myofibers than MyoD-negative FMPs. Transcriptome and surface marker analyses of these cells suggest the importance of myogenic priming for the efficient myogenic engraftment. Our findings suggest the regenerative capability of FMPs in the context of muscle repair and cell therapy for degenerative muscle disease.

Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges.

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Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta

2009-08-01

Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.

Regenerative endodontics--Creating new horizons.

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Dhillon, Harnoor; Kaushik, Mamta; Sharma, Roshni

2016-05-01

Trauma to the dental pulp, physical or microbiologic, can lead to inflammation of the pulp followed by necrosis. The current treatment modality for such cases is non-surgical root canal treatment. The damaged tissue is extirpated and the root canal system prepared. It is then obturated with an inert material such a gutta percha. In spite of advances in techniques and materials, 10%-15% of the cases may end in failure of treatment. Regenerative endodontics combines principles of endodontics, cell biology, and tissue engineering to provide an ideal treatment for inflamed and necrotic pulp. It utilizes mesenchymal stem cells, growth factors, and organ tissue culture to provide treatment. Potential treatment modalities include induction of blood clot for pulp revascularization, scaffold aided regeneration, and pulp implantation. Although in its infancy, successful treatment of damaged pulp tissue has been performed using principles of regenerative endodontics. This field is dynamic and exciting with the ability to shape the future of endodontics. This article highlights the fundamental concepts, protocol for treatment, and possible avenues for research in regenerative endodontics. © 2015 Wiley Periodicals, Inc.

The dissolution kinetics of magnetite under regenerative conditions

International Nuclear Information System (INIS)

Ranganathan, S.

2004-01-01

Dissolution studies of magnetite were carried out under regenerative conditions in dilute chemical decontamination formulations. During regeneration of the formulation, the H + from the strong acid cation exchange resin gets released and the metal is absorbed on the resin. The efficiency of the regenerative process depends on the stability constants of the complexes involved and the selectivity on the ion exchange column. The regenerative condition helps to maintain a constant chelating agent concentration and pH during the dissolution experiment. Such a condition is ideal for obtaining data on the dissolution behaviour of the corrosion products with special application to actual reactor decontamination. The ethylenediaminetetraacetic acid (EDTA) based formulation used was found to be ineffective due to the high stability constant of Fe(III)-EDTA complex, which is not easily cleaved by the cation exchange resin. Hence, knowledge of the kinetics of magnetite dissolution under regenerative condition is of primary importance. The 2,6-pyridinedicarboxylic acid formulation is found to be better for the dissolution of Fe 3 O 4 in both static and regenerative modes in the presence of reductants than nitrilotriacetic acid and EDTA. (orig.)

The dissolution kinetics of magnetite under regenerative conditions

Energy Technology Data Exchange (ETDEWEB)

Ranganathan, S. [New Brunswick Univ., Frederiction (Canada). Dept. of Chemical Engineering; Raghavan, P.S.; Gopalan, R.; Srinivasan, M.P.; Narasimhan, S.V. [Water and Steam Chemistry Lab. of Bhabha Atomic Research Centre (BARC) (India)

2004-07-01

Dissolution studies of magnetite were carried out under regenerative conditions in dilute chemical decontamination formulations. During regeneration of the formulation, the H{sup +} from the strong acid cation exchange resin gets released and the metal is absorbed on the resin. The efficiency of the regenerative process depends on the stability constants of the complexes involved and the selectivity on the ion exchange column. The regenerative condition helps to maintain a constant chelating agent concentration and pH during the dissolution experiment. Such a condition is ideal for obtaining data on the dissolution behaviour of the corrosion products with special application to actual reactor decontamination. The ethylenediaminetetraacetic acid (EDTA) based formulation used was found to be ineffective due to the high stability constant of Fe(III)-EDTA complex, which is not easily cleaved by the cation exchange resin. Hence, knowledge of the kinetics of magnetite dissolution under regenerative condition is of primary importance. The 2,6-pyridinedicarboxylic acid formulation is found to be better for the dissolution of Fe{sub 3}O{sub 4} in both static and regenerative modes in the presence of reductants than nitrilotriacetic acid and EDTA. (orig.)

Retreatment of failed regenerative endodontic of orthodontically treated immature permanent maxillary central incisor: a case report

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Musaed Fahad Al-Tammami

2017-02-01

Full Text Available A revascularization procedure was shown to be the best alternative therapy for immature teeth with necrotic pulp and apical infection. A 12 year old female with a history of trauma to her upper central incisor and a sinus tract was referred for endodontic treatment. She was an active orthodontic patient and had undergone regenerative endodontic treatment for the past 2 years. Clinical examination revealed no response to sensibility, percussion, and palpation tests. The preoperative radiograph showed an open apex and apical rarefaction. The case was diagnosed as previously treated tooth with asymptomatic apical periodontitis. Regenerative endodontic retreatment was performed, and the case was followed for 3 years. Clinical, radiographic, and cone-beam computed tomography follow-up examination revealed an asymptomatic tooth, with evidence of periapical healing and root maturation.

Regenerative Hydride Heat Pump

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Jones, Jack A.

1992-01-01

Hydride heat pump features regenerative heating and single circulation loop. Counterflow heat exchangers accommodate different temperatures of FeTi and LaNi4.7Al0.3 subloops. Heating scheme increases efficiency.

Combined hydraulic and regenerative braking system

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Venkataperumal, R.R.; Mericle, G.E.

1979-08-09

A combined hydraulic and regenerative braking system and method for an electric vehicle is disclosed. The braking system is responsive to the applied hydraulic pressure in a brake line to control the braking of the vehicle to be completely hydraulic up to a first level of brake line pressure, to be partially hydraulic at a constant braking force and partially regenerative at a linearly increasing braking force from the first level of applied brake line pressure to a higher second level of brake line pressure, to be partially hydraulic at a linearly increasing braking force and partially regenerative at a linearly decreasing braking force from the second level of applied line pressure to a third and higher level of applied line pressure, and to be completely hydraulic at a linearly increasing braking force from the third level to all higher applied levels of line pressure.

Regenerative agriculture: merging farming and natural resource conservation profitably.

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LaCanne, Claire E; Lundgren, Jonathan G

2018-01-01

Most cropland in the United States is characterized by large monocultures, whose productivity is maintained through a strong reliance on costly tillage, external fertilizers, and pesticides (Schipanski et al., 2016). Despite this, farmers have developed a regenerative model of farm production that promotes soil health and biodiversity, while producing nutrient-dense farm products profitably. Little work has focused on the relative costs and benefits of novel regenerative farming operations, which necessitates studying in situ , farmer-defined best management practices. Here, we evaluate the relative effects of regenerative and conventional corn production systems on pest management services, soil conservation, and farmer profitability and productivity throughout the Northern Plains of the United States. Regenerative farming systems provided greater ecosystem services and profitability for farmers than an input-intensive model of corn production. Pests were 10-fold more abundant in insecticide-treated corn fields than on insecticide-free regenerative farms, indicating that farmers who proactively design pest-resilient food systems outperform farmers that react to pests chemically. Regenerative fields had 29% lower grain production but 78% higher profits over traditional corn production systems. Profit was positively correlated with the particulate organic matter of the soil, not yield. These results provide the basis for dialogue on ecologically based farming systems that could be used to simultaneously produce food while conserving our natural resource base: two factors that are pitted against one another in simplified food production systems. To attain this requires a systems-level shift on the farm; simply applying individual regenerative practices within the current production model will not likely produce the documented results.

Advanced strategies for end-stage heart failure: combining regenerative approaches with LVAD, a new horizon?

Directory of Open Access Journals (Sweden)

Cheyenne eTseng

2015-04-01

Full Text Available Despite the improved treatment of cardiovascular diseases the population with end-stage heart failure is progressively growing. The scarcity of the gold standard therapy, heart transplantation, demands novel therapeutic approaches. For patients awaiting transplantation ventricular assist devices have been of great benefit on survival. To allow explantation of the assist device and obviate heart transplantation, sufficient and durable myocardial recovery is necessary. However, explant rates so far are low. Combining mechanical circulatory support with regenerative therapies such as cell(-based therapy and biomaterials might give rise to improved long-term results. Although synergistic effects are suggested with mechanical support and stem cell therapy, evidence in both preclinical and clinical setting is lacking. This review focuses on advanced and innovative strategies for the treatment of end-stage heart failure and furthermore appraises clinical experience with combined strategies.

The process of translation and linguistic validation of the Functional Assessment of Cancer Therapy-Brain quality of life instrument from English to Malayalam: The challenges faced

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Durgapoorna Menon

2017-01-01

Full Text Available Aim: Both brain tumors and their treatments have a major negative impact on the quality of life (QoL. EORTC BN20 and Functional Assessment of Cancer Therapy-Brain (FACT-BR are the most commonly used tools to assess QoL. The FACT-BR is a 23-item questionnaire, especially about the psychosocial aspects of QoL. This paper describes the challenges we faced during the process of translation and validation of the FACT-BR into Malayalam. Methods: We first screened the patients to ensure their mental status was satisfactory and that they could communicate well in both languages. According to the Functional Assessment of Chronic Illness Therapy methodology, there were two forward translations from English to Malayalam by two independent translators, a reconciliation of the two forward translations, a back-translation into English, a review/finalization by a fifth translator, proofreading, and then testing on a small cohort of patients. Results: The whole process of translation was fraught with small and large hurdles – from small technical issues to the gaps in sociocultural norms. The sub item BR 7, due to the lack of an exact equivalent word, had issues that persisted up to the validation phase. The postquestionnaire debriefing interviews confirmed that the translations were well understood and conceptually equivalent to the original English one. Conclusions: Translation of the FACT-BR into Malayalam nearly completely reproduced the concepts of the original English questionnaire, as proved in the subsequent validation process.

Genetic engineering for skeletal regenerative medicine.

Science.gov (United States)

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.

Stem cell therapy clinical research: A regulatory conundrum for academia.

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Nagpal, Anjali; Juttner, Chris; Hamilton-Bruce, Monica Anne; Rolan, Paul; Koblar, Simon A

2017-12-01

The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Autonomous Operation of Super-Regenerative Receiver in BAN

NARCIS (Netherlands)

Kalyanasundaram, P.; Huang, L.; Dolmans, G.; Imamura, K.

2012-01-01

Super-regenerative receiver is one of the potential candidates to achieve ultra low power wireless communication in body area network (BAN). The main limitations of the super-regenerative receiver include the difficulty in choosing a good quench waveform to optimize its sensitivity and selectivity,

Adaptive controller for regenerative and friction braking system

Science.gov (United States)

Davis, Roy I.

1990-01-01

A regenerative and friction braking system for a vehicle having one or more roadwheels driven by an electric traction motor includes a driver responsive device for producing a brake demand signal having a magnitude corresponding to the level of braking force selected by the driver and friction and regenerative brakes operatively connected with the roadwheels of the vehicle. A system according to this invention further includes control means for operating the friction and regenerative braking subsystems so that maximum brake torques sustainable by the roadwheels of the vehicle without skidding or slipping will not be exceeded.

Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head

Science.gov (United States)

2012-01-01

Avascular necrosis (AVN) of the femoral head is a debilitating disease of multifactorial genesis, predominately affects young patients, and often leads to the development of secondary osteoarthritis. The evolving field of regenerative medicine offers promising treatment strategies using cells, biomaterial scaffolds, and bioactive factors, which might improve clinical outcome. Early stages of AVN with preserved structural integrity of the subchondral plate are accessible to retrograde surgical procedures, such as core decompression to reduce the intraosseous pressure and to induce bone remodeling. The additive application of concentrated bone marrow aspirates, ex vivo expanded mesenchymal stem cells, and osteogenic or angiogenic growth factors (or both) holds great potential to improve bone regeneration. In contrast, advanced stages of AVN with collapsed subchondral bone require an osteochondral reconstruction to preserve the physiological joint function. Analogously to strategies for osteochondral reconstruction in the knee, anterograde surgical techniques, such as osteochondral transplantation (mosaicplasty), matrix-based autologous chondrocyte implantation, or the use of acellular scaffolds alone, might preserve joint function and reduce the need for hip replacement. This review summarizes recent experimental accomplishments and initial clinical findings in the field of regenerative medicine which apply cells, growth factors, and matrices to address the clinical problem of AVN. PMID:22356811

Regenerative Medicine for Periodontal and Peri-implant Diseases.

Science.gov (United States)

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. © International & American Associations for Dental Research 2015.

Silibinin inhibits translation initiation: implications for anticancer therapy.

Science.gov (United States)

Lin, Chen-Ju; Sukarieh, Rami; Pelletier, Jerry

2009-06-01

Silibinin is a nontoxic flavonoid reported to have anticancer properties. In this study, we show that silibinin exhibits antiproliferative activity on MCF-7 breast cancer cells. Exposure to silibinin leads to a concentration-dependent decrease in global protein synthesis associated with reduced levels of eukaryotic initiation factor 4F complex. Moreover, polysome profile analysis of silibinin-treated cells shows a decrease in polysome content and translation of cyclin D1 mRNA. Silibinin exerts its effects on translation initiation by inhibiting the mammalian target of rapamycin signaling pathway by acting upstream of TSC2. Our results show that silibinin blocks mammalian target of rapamycin signaling with a concomitant reduction in translation initiation, thus providing a possible molecular mechanism of how silibinin can inhibit growth of transformed cells.

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

Science.gov (United States)

Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

2015-01-01

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

An Intelligent Regenerative Braking Strategy for Electric Vehicles

Directory of Open Access Journals (Sweden)

Zhibin Song

2011-09-01

Full Text Available Regenerative braking is an effective approach for electric vehicles (EVs to extend their driving range. A fuzzy-logic-based regenerative braking strategy (RBS integrated with series regenerative braking is developed in this paper to advance the level of energy-savings. From the viewpoint of securing car stability in braking operations, the braking force distribution between the front and rear wheels so as to accord with the ideal distribution curve are considered to prevent vehicles from experiencing wheel lock and slip phenomena during braking. Then, a fuzzy RBS using the driver’s braking force command, vehicle speed, battery SOC, battery temperature are designed to determine the distribution between friction braking force and regenerative braking force to improve the energy recuperation efficiency. The experimental results on an “LF620” prototype EV validated the feasibility and effectiveness of regenerative braking and showed that the proposed fuzzy RBS was endowed with good control performance. The maximum driving range of LF620 EV was improved by 25.7% compared with non-RBS conditions.

Evaluation strategy of regenerative braking energy for supercapacitor vehicle.

Science.gov (United States)

Zou, Zhongyue; Cao, Junyi; Cao, Binggang; Chen, Wen

2015-03-01

In order to improve the efficiency of energy conversion and increase the driving range of electric vehicles, the regenerative energy captured during braking process is stored in the energy storage devices and then will be re-used. Due to the high power density of supercapacitors, they are employed to withstand high current in the short time and essentially capture more regenerative energy. The measuring methods for regenerative energy should be investigated to estimate the energy conversion efficiency and performance of electric vehicles. Based on the analysis of the regenerative braking energy system of a supercapacitor vehicle, an evaluation system for energy recovery in the braking process is established using USB portable data-acquisition devices. Experiments under various braking conditions are carried out. The results verify the higher efficiency of energy regeneration system using supercapacitors and the effectiveness of the proposed measurement method. It is also demonstrated that the maximum regenerative energy conversion efficiency can reach to 88%. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Induced pluripotent stem cells and their implication for regenerative medicine.

Science.gov (United States)

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.

Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine.

Science.gov (United States)

Wu, Xiuwen; Ren, Jianan; Li, Jieshou

2012-05-01

The use of tissue-engineering techniques such as stem-cell therapy to renew injured tissues is a promising strategy in regenerative medicine. As a cell-delivery vehicle, fibrin glues (FG) facilitate cell attachment, growth and differentiation and, ultimately, tissue formation and organization by its three-dimensional structure. Numerous studies have provided evidence that stromal cells derived from bone marrow (bone marrow stromal cells; BMSC) and adipose tissue (adipose-derived stromal cells; ADSC) contain a population of adult multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells that can differentiate into several lineages. By combining MSC with FG, the implantation could take advantage of the mutual benefits. Researchers and physicians have pinned their hopes on stem cells for developing novel approaches in regenerative medicine. This review focuses on the therapeutic potential of MSC with FG in bone defect reconstruction, cartilage and tendon injury repair, ligament, heart and nerve regeneration, and, furthermore, wound healing.

Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds.

Science.gov (United States)

Wu, Tsai-Jung; Tzeng, Yan-Kai; Chang, Wei-Wei; Cheng, Chi-An; Kuo, Yung; Chien, Chin-Hsiang; Chang, Huan-Cheng; Yu, John

2013-09-01

Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(-)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

Strategic Plans to Promote Head and Neck Cancer Translational Research Within the Radiation Therapy Oncology Group: A Report From the Translational Research Program

International Nuclear Information System (INIS)

Chung, Christine H.; Wong, Stuart; Ang, K. Kian; Hammond, Elizabeth H.; Dicker, Adam P.; Harari, Paul M.; Le, Quynh-Thu

2007-01-01

Head and neck cancer is the fifth most common cancer in the United States, with an overall survival rate of approximately 40-50%. In an effort to improve patient outcomes, research efforts designed to maximize benefit and reduce toxicities of therapy are in progress. Basic research in cancer biology has accelerated this endeavor and provided preclinical data and technology to support clinically relevant advances in early detection, prognostic and predictive biomarkers. Recent completion of the Human Genome Project has promoted the rapid development of novel 'omics' technologies that allow more broad based study from a systems biology perspective. However, clinically relevant application of resultant gene signatures to clinical trials within cooperative groups has advanced slowly. In light of the large numbers of variables intrinsic to biomarker studies, validation of preliminary data for clinical implementation presents a significant challenge and may only be realized with large trials that involve significant patient numbers. The Radiation Therapy Oncology Group (RTOG) Head and Neck Cancer Translational Research Program recognizes this problem and brings together three unique features to facilitate this research: (1) availability of large numbers of clinical specimens from homogeneously treated patients through multi-institutional clinical trials; (2) a team of physicians, scientists, and staff focused on patient-oriented head-and-neck cancer research with the common goal of improving cancer care; and (3) a funding mechanism through the RTOG Seed Grant Program. In this position paper we outline strategic plans to further promote translational research within the framework of the RTOG

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

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Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

Gene therapy for cartilage and bone tissue engineering

CERN Document Server

Hu, Yu-Chen

2014-01-01

"Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

Knowledge Translation to Optimize Adult Inpatient Glycemic Management with Basal Bolus Insulin Therapy and Improve Patient Outcomes.

Science.gov (United States)

Helmle, Karmon E; Chacko, Sunita; Chan, Trevor; Drake, Alison; Edwards, Alun L; Moore, Glenda E; Philp, Leta C; Popeski, Naomi; Roedler, Rhonda L; Rogers, Edwin J R; Zimmermann, Gabrielle L; McKeen, Julie

2017-12-27

To develop and evaluate a Basal Bolus Insulin Therapy (BBIT) Knowledge Translation toolkit to address barriers to adoption of established best practice with BBIT in the care of adult inpatients. This study was conducted in 2 phases and focused on the hospitalist provider group across 4 acute care facilities in Calgary. Phase 1 involved a qualitative evaluation of provider and site specific barriers and facilitators, which were mapped to validated interventions using behaviour change theory. This informed the co-development and optimization of the BBIT Knowledge Translation toolkit, with each tool targeting a specific barrier to improved diabetes care practice, including BBIT ordering. In Phase 2, the BBIT Knowledge Translation toolkit was implemented and evaluated, focusing on BBIT ordering frequency, as well as secondary outcomes of hyperglycemia (patient-days with BG >14.0 mmol/L), hypoglycemia (patient-days with BG Knowledge Translation toolkit resulted in a significant 13% absolute increase in BBIT ordering. Hyperglycemic patient-days were significantly reduced, with no increase in hypoglycemia. There was a significant, absolute 14% reduction in length of stay. The implementation of an evidence-informed, multifaceted BBIT Knowledge Translation toolkit effectively reduced a deeply entrenched in-patient diabetes care gap. The resulting sustained practice change improved patient clinical and system resource utilization outcomes. This systemic approach to implementation will guide further scale and spread of glycemic optimization initiatives. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Clinical considerations for regenerative endodontic procedures.

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Geisler, Todd M

2012-07-01

The management of a tooth with incomplete root maturation and a necrotic pulp is an endodontic and a restorative challenge. Apexification procedures alone leave the tooth in a weakened state and at risk for reinfection. Regenerative endodontic procedures potentially offer advantages, including the possibility of hard tissue deposition and continued root development. Case studies have reported regeneration of human pulplike tissues in vivo, but there is no protocol that reliably regenerates pulplike tissue. This article summarizes historical, current, and future regenerative treatment approaches. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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. © 2013 Elsevier Inc. All rights reserved.

Challenging the FDA's authority to regulate autologous adult stem cells for therapeutic use: Celltex therapeutics' partnership with RNL Bio, substantial medical risks, and the implications of United States v. Regenerative Sciences.

Science.gov (United States)

Drabiak-Syed, Katherine

2013-01-01

This Article examines the convergence of three corporations that have attempted to capitalize on translating emerging research into clinical procedures by manufacturing and facilitating the process for patients to obtain mesenchymal stem cell (MSC) injections. Although the Food and Drug Administration (FDA) has asserted its authority to regulate somatic cell therapy products like MSCs under the Public Health Service Act and the Food, Drug, and Cosmetic Act, some manufacturers have attempted to circumvent FDA regulation through various mechanisms and argue that their products do not fall within the definition of a biological product or drug. However, scientific knowledge of using MSCs for clinical therapy remains in its infancy, and MSCs pose a number of serious risks to patients. This Article focuses on the development of Celltex, a company based in Sugar Land, Texas that manufactures and facilitates the injection of autologous MSCs; RNL Bio, a company that licenses its operations technology to Celltex; and Regenerative Sciences, a company based in Broomfield, Colorado that was recently involved in litigation with the FDA. Corporate circumvention of intended regulatory oversight exposes patients to potentially inefficacious products that could contribute to serious medical injuries such as viruses, myocardial infarction, cancer, or death.

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Directory of Open Access Journals (Sweden)

Kenneth Maiese

2016-01-01

Full Text Available Throughout the globe, diabetes mellitus (DM is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1 and mTOR Complex 2 (mTORC2 and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K, protein kinase B (Akt, AMP activated protein kinase (AMPK, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae (SIRT1, Wnt1 inducible signaling pathway protein 1 (WISP1, and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Center for Neuroscience & Regenerative Medicine

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Federal Laboratory Consortium — The Center for Neuroscience and Regenerative Medicine (CNRM) was established as a collaborative intramural federal program involving the U.S. Department of Defense...

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

NARCIS (Netherlands)

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C; Niesters, Bert

2008-01-01

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

Stem cell bioprinting for applications in regenerative medicine.

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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. © 2016 New York Academy of Sciences.

A high-power compact regenerative amplifier FEL

International Nuclear Information System (INIS)

Nguyen, D.C.; Sheffield, R.L.; Fortgang, C.M.; Kinross-Wright, J.M.; Ebrahim, N.A.; Goldstein, J.C.

1997-01-01

The Regenerative Amplifier FEL (RAFEL) is a new FEL approach aimed at achieving the highest optical power from a compact rf-linac FEL. The key idea is to feed back a small fraction ( 5 in single pass) wiggler to enable the FEL to reach saturation in a few passes. This paper summarizes the design of a high-power compact regenerative amplifier FEL and describes the first experimental demonstration of the RAFEL concept

Early Orthodontic Tooth Movement into Regenerative Bony Defects: A Case Report.

Science.gov (United States)

Tsai, Hui-Chen; Yao, Chung-Chen Jane; Wong, Man-Ying

Early orthodontic tooth movement following regenerative surgery is controversial. In this case, during protraction of the maxillary right first premolar to substitute for the long-term missing maxillary right canine, Bio-Oss and Bio-Gide were used for lateral ridge augmentation at the area of the maxillary right lateral incisor and to cover the denuded surface at the buccal side of the first premolar. Orthodontic tooth movement (OTM) commenced 2 weeks after regenerative surgery. After 8 months, new bone formation was observed on the root surface of the first premolar during implant surgery. A cone beam computed tomography scan taken 1.5 years postsurgery revealed good maintenance of regenerative bone at the same site. This satisfactory outcome of early OTM following regenerative surgery suggests biomechanical stimulation may not jeopardize the regenerative effect.

Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments

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Bizunesh M. Borena

2015-04-01

Full Text Available Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called “restitutio ad integrum”. Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies.

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.

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Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

2017-10-05

Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation." Original articles and critical reviews on the topics were selected. Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

Age-old wisdom concerning cell-based therapies with added knowledge in the stem cell era: our perspectives

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Preethy S

2013-04-01

Full Text Available Senthilkumar Preethy,1,2 Sudhakar John,1 Jegatheesan Saravana Ganesh,1 Thangavelu Srinivasan,1 Hiroshi Terunuma,3 Masaru Iwasaki,4 Samuel J Abraham1,4 1Nichi-In Centre for Regenerative Medicine, 2Hope Foundation Trust, Chennai, India; 3Biotherapy Institute of Japan, Tokyo, 4Yamanashi University School of Medicine, Chuo, Japan Abstract: Among the various strategies providing a cure for illness, cell-based therapies have caught the attention of the world with the advent of the "stem cell" era. Our inherent understanding indicates that stem cells have been in existence since the birth of multicellular organisms. However, the formal discovery of stem cells in the last century, followed by their intricate and extensive analysis, has led to clinical and translational efforts with the aim of using them in the treatment of conditions which don't have a definitive therapeutic strategy, has fueled our interest and expectations. Technological advances in our ability to study their cellular components in depth, along with surface markers and other finer constituents, that were unknown until last century, have improved our understanding, leading to several novel applications. This has created a need to establish guidelines, and in that process, there are expressed understandings and views which describe cell therapy along lines similar to that of biologic products, drugs, and devices. However, the age-old wisdom of using cells as tools for curing illness should not be misled by recent knowledge, to make cell therapy using highly complex stem cells equal to factory-synthesized and reproducible chemical compounds, drugs, or devices. This article analyses the differences between these two entities from various perspectives. Keywords: cell transplantation, drugs, regenerative medicine, stem cells

Regenerative Endodontic Treatment with Orthodontic Treatment in a Tooth with Dens Evaginatus: A Case Report with a 4-year Follow-up.

Science.gov (United States)

Natera, Marianella; Mukherjee, Padma M

2018-06-01

Dens evaginatus is a developmental tooth anomaly in which an extra cusp or tubercle protrudes on the occlusal surface of the tooth along with some pulpal tissue. Because of the fragile nature of the protrusion, these teeth are often at risk of pulpal exposure. When this occurs in an immature tooth, regenerative endodontic treatment may be a good treatment approach to promote root formation. There is limited literature that documents the occurrence of orthodontic treatment in teeth that have undergone regenerative endodontic therapy using triple antibiotic paste. Here we present a case of an immature premolar tooth with dens evaginatus that was diagnosed with pulp necrosis and chronic apical abscess. The tooth was treated with regenerative endodontic treatment; after which, the patient received orthodontic treatment with fixed appliances for 2 years. The tooth responded favorably to the regenerative endodontic treatment and orthodontic tooth movement. Clinically and radiographically, all the follow-up examinations revealed an asymptomatic tooth with evidence of periapical healing with stunted root development. The tooth remained asymptomatic even after 4 years. The regenerative endodontic procedure (REP) was successful in treating an immature permanent premolar with pulp necrosis and apical periodontitis with dens evaginatus. In this case, the tooth treated with an REP responded to orthodontic treatment similar to the nonendodontically treated teeth. Further studies are recommended to clarify the precise effects of orthodontic treatment on teeth treated with an REP. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Giant hepatic regenerative nodules in Alagille syndrome

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Rapp, Jordan B. [Lewis Katz School of Medicine at Temple University, Department of Radiology, Temple University Hospital, Philadelphia, PA (United States); Bellah, Richard D.; Anupindi, Sudha A. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Maya, Carolina [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Pawel, Bruce R. [University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); The Children' s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Philadelphia, PA (United States)

2017-02-15

Children with Alagille syndrome undergo surveillance radiologic examinations as they are at risk for developing cirrhosis and hepatocellular carcinoma. There is limited literature on the imaging of liver masses in Alagille syndrome. We report the ultrasound (US) and magnetic resonance imaging (MRI) appearances of incidental benign giant hepatic regenerative nodules in this population. To describe the imaging findings of giant regenerative nodules in patients with Alagille syndrome. A retrospective search of the hospital database was performed to find all cases of hepatic masses in patients with Alagille syndrome during a 10-year period. Imaging, clinical charts, laboratory data and available pathology were reviewed and analyzed and summarized for each patient. Twenty of 45 patients with confirmed Alagille syndrome had imaging studies. Of those, we identified six with giant focal liver masses. All six patients had large central hepatic masses that were remarkably similar on US and MRI, in addition to having features of cirrhosis. In each case, the mass was located in hepatic segment VIII and imaging showed the mass splaying the main portal venous branches at the hepatic hilum, as well as smaller portal and hepatic venous branches coursing through them. On MRI, signal intensity of the mass was isointense to liver on T1-weighted sequences in four of six patients, but hyperintense on T1 in two of six patients. In all six cases, the mass was hypointense on T2- weighted sequences. The mass post-contrast was isointense to adjacent liver in all phases in five the cases. Five out of six patients had pathological correlation demonstrating preserved ductal architecture confirming the final diagnosis of a regenerative nodule. Giant hepatic regenerative nodules with characteristic US and MR features can occur in patients with Alagille syndrome with underlying cirrhosis. Recognizing these lesions as benign giant hepatic regenerative nodules should, thereby, mitigate any need for

Giant hepatic regenerative nodules in Alagille syndrome

International Nuclear Information System (INIS)

Rapp, Jordan B.; Bellah, Richard D.; Anupindi, Sudha A.; Maya, Carolina; Pawel, Bruce R.

2017-01-01

Children with Alagille syndrome undergo surveillance radiologic examinations as they are at risk for developing cirrhosis and hepatocellular carcinoma. There is limited literature on the imaging of liver masses in Alagille syndrome. We report the ultrasound (US) and magnetic resonance imaging (MRI) appearances of incidental benign giant hepatic regenerative nodules in this population. To describe the imaging findings of giant regenerative nodules in patients with Alagille syndrome. A retrospective search of the hospital database was performed to find all cases of hepatic masses in patients with Alagille syndrome during a 10-year period. Imaging, clinical charts, laboratory data and available pathology were reviewed and analyzed and summarized for each patient. Twenty of 45 patients with confirmed Alagille syndrome had imaging studies. Of those, we identified six with giant focal liver masses. All six patients had large central hepatic masses that were remarkably similar on US and MRI, in addition to having features of cirrhosis. In each case, the mass was located in hepatic segment VIII and imaging showed the mass splaying the main portal venous branches at the hepatic hilum, as well as smaller portal and hepatic venous branches coursing through them. On MRI, signal intensity of the mass was isointense to liver on T1-weighted sequences in four of six patients, but hyperintense on T1 in two of six patients. In all six cases, the mass was hypointense on T2- weighted sequences. The mass post-contrast was isointense to adjacent liver in all phases in five the cases. Five out of six patients had pathological correlation demonstrating preserved ductal architecture confirming the final diagnosis of a regenerative nodule. Giant hepatic regenerative nodules with characteristic US and MR features can occur in patients with Alagille syndrome with underlying cirrhosis. Recognizing these lesions as benign giant hepatic regenerative nodules should, thereby, mitigate any need for

Micro-Scale Regenerative Heat Exchanger

Science.gov (United States)

Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

2004-01-01

A micro-scale regenerative heat exchanger has been designed, optimized and fabricated for use in a micro-Stirling device. Novel design and fabrication techniques enabled the minimization of axial heat conduction losses and pressure drop, while maximizing thermal regenerative performance. The fabricated prototype is comprised of ten separate assembled layers of alternating metal-dielectric composite. Each layer is offset to minimize conduction losses and maximize heat transfer by boundary layer disruption. A grating pattern of 100 micron square non-contiguous flow passages were formed with a nominal 20 micron wall thickness, and an overall assembled ten-layer thickness of 900 microns. Application of the micro heat exchanger is envisioned in the areas of micro-refrigerators/coolers, micropower devices, and micro-fluidic devices.

Erich Regener and the ionisation maximum of the atmosphere

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Carlson, P.; Watson, A. A.

2014-12-01

In the 1930s the German physicist Erich Regener (1881-1955) did important work on the measurement of the rate of production of ionisation deep under water and in the atmosphere. Along with one of his students, Georg Pfotzer, he discovered the altitude at which the production of ionisation in the atmosphere reaches a maximum, often, but misleadingly, called the Pfotzer maximum. Regener was one of the first to estimate the energy density of cosmic rays, an estimate that was used by Baade and Zwicky to bolster their postulate that supernovae might be their source. Yet Regener's name is less recognised by present-day cosmic ray physicists than it should be, largely because in 1937 he was forced to take early retirement by the National Socialists as his wife had Jewish ancestors. In this paper we briefly review his work on cosmic rays and recommend an alternative naming of the ionisation maximum. The influence that Regener had on the field through his son, his son-in-law, his grandsons and his students, and through his links with Rutherford's group in Cambridge, is discussed in an appendix. Regener was nominated for the Nobel Prize in Physics by Schrödinger in 1938. He died in 1955 at the age of 73.

Electrolyte for batteries with regenerative solid electrolyte interface

Science.gov (United States)

Xiao, Jie; Lu, Dongping; Shao, Yuyan; Bennett, Wendy D.; Graff, Gordon L.; Liu, Jun; Zhang, Ji-Guang

2017-08-01

An energy storage device comprising: an anode; and a solute-containing electrolyte composition wherein the solute concentration in the electrolyte composition is sufficiently high to form a regenerative solid electrolyte interface layer on a surface of the anode only during charging of the energy storage device, wherein the regenerative layer comprises at least one solute or solvated solute from the electrolyte composition.

Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

Science.gov (United States)

Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

2018-03-16

RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

Hurdles in tissue engineering/regenerative medicine product commercialization: a pilot survey of governmental funding agencies and the financial industry.

Science.gov (United States)

Bertram, Timothy A; Tentoff, Edward; Johnson, Peter C; Tawil, Bill; Van Dyke, Mark; Hellman, Kiki B

2012-11-01

The Tissue Engineering and Regenerative Medicine International Society of the Americas (TERMIS-AM) Industry Committee conducted a semiquantitative opinion survey in 2010 to delineate potential hurdles to commercialization perceived by the TERMIS constituency groups that participate in the stream of technology commercialization (academia, start-up companies, development-stage companies, and established companies). A significant hurdle identified consistently by each group was access to capital for advancing potential technologies into development pathways leading to commercialization. A follow-on survey was developed by the TERMIS-AM Industry Committee to evaluate the financial industry's perspectives on investing in regenerative medical technologies. The survey, composed of 15 questions, was developed and provided to 37 investment organizations in one of three sectors (governmental, private, and public investors). The survey was anonymous and confidential with sector designation the only identifying feature of each respondent's organization. Approximately 80% of the survey was composed of respondents from the public (n=14) and private (n=15) sectors. Each respondent represents one investment organization with the potential of multiple participants participating to form the organization's response. The remaining organizations represented governmental agencies (n=8). Results from this survey indicate that a high percentage ($2MM into regenerative medical companies at the different stages of a company's life cycle. Investors recognized major hurdles to this emerging industry, including regulatory pathway, clinical translation, and reimbursement of these new products. Investments in regenerative technologies have been cyclical over the past 10-15 years, but investors recognized a 1-5-year investment period before the exit via Merger and Acquisition (M&A). Investors considered musculoskeletal products and their top technology choice with companies in the clinical stage

Translational research in medicine

Directory of Open Access Journals (Sweden)

Bakir Mehić

2011-05-01

��t continue to be regarded as independent disciplines. Integrated training in translational research methods is needed for clinicians, guideline writers, grant awarding bodies, and policy makers, in order to redress current biases in funding and research publications, in order to reflect better the balance of research efforts which are necessary for better assessment of complex evidence-bases, to integrate effective and sensitive interventions with supporting environmental changes, and to encourage continuous improvement of evidence based public policies.[5]There are three major obstacles to effective translational medicine. The first is the challenge of translating basic science discoveries into clinical studies. The second hurdle is the translation of clinical studies into medical practice and health care policy.[6] A third obstacle to effective translational medicine is also philosophical. It is a fact that the available standard therapies for most common diseases are less efficacious than they are believed by the Public to be and significant funds are allocated to maintain this “placebo” effect through standard care. Proportionately, very little is spent to identify truly effective therapies. Finally, it may be a mistake to think that basic science, without observations from the clinic and without epidemiological findings of possible associations between different noxes and disease, will efficiently produce the novel therapies that we are eager to test.To pursue the promotion of translational research, the Editorial Board strongly supports basic scientific work and such that is a combination of basic research and clinical praxis.

Platelet concentrates: Bioengineering dentistry′s regenerative dreams

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Sushma Naag

2015-01-01

Full Text Available Technological advances in the fields of medicine and allied sciences had given much needed momentum into the field of molecular biology and regenerative medicine. They indeed provided a boost to innovate new yields for both hard tissue and soft tissue regeneration in dentistry. One among them is the use of platelet concentrates (platelet rich plasma [PRP], platelet rich fibrin [PRF]. Autologous concentrate of blood platelets with a suspension of growth factors offers an enhanced healing of hard and soft tissues. It is an auxiliary benefit for an operator to be aware of platelet concentrates and its healing properties for delivering unsurpassed oral health care to patients. The current article outlines the principles, objectives and clinical insight to the regenerative potential of platelet concentrates in various fields of dentistry. The search words of the PubMed data base were PRF and other permutations of keywords such as "PRP dentistry", PRF dentistry, PRF regenerative dentistry.

Intestinal Stem Cells to Advance Drug Development, Precision, and Regenerative Medicine: A Paradigm Shift in Translational Research.

Science.gov (United States)

Mochel, Jonathan P; Jergens, Albert E; Kingsbury, Dawn; Kim, Hyun Jung; Martín, Martín G; Allenspach, Karin

2017-12-12

Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at lower costs compared with live animal studies. Importantly, because they are derived from individuals with different genotypes, environmental risk factors and drug sensitivity profiles, organoids are a highly relevant screening system for personalized therapy in both human and veterinary medicine. Lastly, and in the context of patient-specific congenital diseases, orthotopic transplantation of engineered organoids could repair and/or replace damaged epithelial tissues reported in various GI diseases, such as inflammatory bowel disease, cystic fibrosis, and tuft enteropathy. Ongoing translational research on organoids derived from dogs with naturally occurring digestive disorders has the potential to improve the predictability of preclinical models used for optimizing the therapeutic management of severe chronic enteropathies in human patients.

Stem cell therapy in spinal trauma: Does it have scientific validity?

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Harvinder Singh Chhabra

2015-01-01

Full Text Available Stem cell-based interventions aim to use special regenerative cells (stem cells to facilitate neuronal function beyond the site of the injury. Many studies involving animal models of spinal cord injury (SCI suggest that certain stem cell-based therapies may restore function after SCI. Currently, in case of spinal cord injuries, new discoveries with clinical implications have been continuously made in basic stem cell research, and stem cell-based approaches are advancing rapidly toward application in patients. There is a huge base of preclinical evidence in vitro and in animal models which suggests the safety and clinical efficacy of cellular therapies after SCI. Despite this, data from clinical studies is not very encouraging and at times confounding. Here, we have attempted to cover preclinical and clinical evidence base dealing with safety, feasibility and efficacy of cell based interventions after SCI. The limitations of preclinical data and the reasons underlying its failure to translate in a clinical setting are also discussed. Based on the evidence base, it is suggested that a multifactorial approach is required to address this situation. Need for standardized, stringently designed multi-centric clinical trials for obtaining validated proof of evidence is also highlighted.

Taking Brief Strategic Family Therapy from Bench to Trench: Evidence Generation Across Translational Phases.

Science.gov (United States)

Horigian, Viviana E; Anderson, Austen R; Szapocznik, José

2016-09-01

In this article, we review the research evidence generated over 40 years on Brief Strategic Family Therapy illustrating the NIH stages of intervention development and highlighting the translational process. Basic research (Stage 0) led to the discovery of the characteristics of the population and the nature of the problems that needed to be addressed. This step informed the selection of an intervention model that addressed the problems presented by the population, but in a fashion that was congruent with the population's culture, defined in terms of its value orientations. From this basic research, an intervention that integrated structural and strategic elements was selected and refined through testing (Stage I). The second stage of translation (Stage II) included efficacy trials of a specialized engagement module that responded to challenges to the provision of services. It also included several other efficacy trials that documented the effects of the intervention, mostly in research settings or with research therapists. Stages III/IV in the translational process led to the testing of the effectiveness of the intervention in real-world settings with community therapists and some oversight from the developer. This work revealed that an implementation/organizational intervention was required to achieve fidelity and sustainability of the intervention in real-world settings. The work is currently in Stage V in which new model development led to an implementation intervention that can ensure fidelity and sustainability. Future research will evaluate the effectiveness of the current implementation model in increasing adoption, fidelity, and long-term sustainability in real-world settings. © 2016 Family Process Institute.

A Comprehensive Review of the Techniques on Regenerative Shock Absorber Systems

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Ran Zhang

2018-05-01

Full Text Available In this paper, the current technologies of the regenerative shock absorber systems have been categorized and evaluated. Three drive modes of the regenerative shock absorber systems, namely the direct drive mode, the indirect drive mode and hybrid drive mode are reviewed for their readiness to be implemented. The damping performances of the three different modes are listed and compared. Electrical circuit and control algorithms have also been evaluated to maximize the power output and to deliver the premium ride comfort and handling performance. Different types of parameterized road excitations have been applied to vehicle suspension systems to investigate the performance of the regenerative shock absorbers. The potential of incorporating nonlinearity into the regenerative shock absorber design analysis is discussed. The research gaps for the comparison of the different drive modes and the nonlinearity analysis of the regenerative shock absorbers are identified and, the corresponding research questions have been proposed for future work.

Public-private partnerships in translational medicine: concepts and practical examples.

Science.gov (United States)

Luijten, Peter R; van Dongen, Guus A M S; Moonen, Chrit T; Storm, Gert; Crommelin, Daan J A

2012-07-20

The way forward in multidisciplinary research according to former NIH's director Elias Zerhouni is to engage in predictive, personalized, preemptive and participatory medicine. For the creation of the optimal innovation climate that would allow for such a strategy, public-private partnerships have been widely proposed as an important instrument. Public-private partnerships have become an important instrument to expedite translational research in medicine. The Netherlands have initiated three large public-private partnerships in the life sciences and health area to facilitate the translation of valuable basic scientific concepts to new products and services in medicine. The focus of these partnerships has been on drug development, improved diagnosis and regenerative medicine. The Dutch model of public-private partnership forms the blueprint of a much larger European initiative called EATRIS. This paper will provide practical examples of public-private partnerships initiated to expedite the translation of new technology for drug development towards the clinic. Three specific technologies are in focus: companion diagnostics using nuclear medicine, the use of ultra high field MRI to generate sensitive surrogate endpoints based on endogenous contrast, and MRI guidance for High Intensity Focused Ultrasound mediated drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease.

Science.gov (United States)

Hickson, LaTonya J; Eirin, Alfonso; Lerman, Lilach O

2016-04-01

Chronic kidney disease (CKD) is a global health care burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including proangiogenic, anti-inflammatory, and antifibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This Review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Perivascular cells for regenerative medicine

NARCIS (Netherlands)

M. Crisan (Mihaela); M. Corselli (Mirko); W.C. Chen (William); B. Péault (Bruno)

2012-01-01

textabstractMesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We

The role of the Istituto Superiore di Sanità as the competent authority for Phase I trials in the translation of advanced therapies

Directory of Open Access Journals (Sweden)

Patrizia Popoli

2011-01-01

Full Text Available Advanced therapy medicinal products (ATMP can offer new, effective therapeutic options for the treatment of severe illnesses, including cancer, neurodegenerative and cardiovascular diseases. Translation of advanced therapies to the clinic has been slow despite significant academic research from academia and foundations. The implementation of 2001/20 Directive in Italy established that the development of an ATMP should follow the GXP rules - good manufacturing practice (GMP for production, good laboratory practice (GLP for non clinical safety studies and good clinical practice (GCP for clinical trials. The high costs of GCP application and the needs for GMP facilities are perceived as the most important bottlenecks for the development of ATMP. Here it is pointed out that a strategic cooperation between different actors (academia, industry and experts in regulatory issues is strongly needed. In particular, it is highlighted that the Istituto Superiore di Sanità, as the competent authority for the authorization of Phase I clinical trials, has a specific responsibility in fostering the translation of safe and effective therapies for human diseases.

The role of the Istituto Superiore di Sanità as the competent authority for Phase I trials in the translation of advanced therapies.

Science.gov (United States)

Popoli, Patrizia; Cometa, Maria Francesca; Fabi, Fulvia; Meneguz, Annarita

2011-01-01

Advanced therapy medicinal products (ATMP) can offer new, effective therapeutic options for the treatment of severe illnesses, including cancer, neurodegenerative and cardiovascular diseases. Translation of advanced therapies to the clinic has been slow despite significant academic research from academia and foundations. The implementation of 2001/20 Directive in Italy established that the development of an ATMP should follow the GXP rules - good manufacturing practice (GMP) for production, good laboratory practice (GLP) for non clinical safety studies and good clinical practice (GCP) for clinical trials. The high costs of GCP application and the needs for GMP facilities are perceived as the most important bottlenecks for the development of ATMP. Here it is pointed out that a strategic cooperation between different actors (academia, industry and experts in regulatory issues) is strongly needed. In particular, it is highlighted that the Istituto Superiore di Sanità, as the competent authority for the authorization of Phase I clinical trials, has a specific responsibility in fostering the translation of safe and effective therapies for human diseases.

Therapeutic Potential, Challenges and Future Perspective of Cancer Stem Cells in Translational Oncology: A Critical Review.

Science.gov (United States)

Shukla, Gaurav; Khera, Harvinder Kour; Srivastava, Amit Kumar; Khare, Piush; Patidar, Rahul; Saxena, Rajiv

2017-01-01

Stem cell research is a rapidly developing field that offers effective treatment for a variety of malignant and non-malignant diseases. Stem cell is a regenerative medicine associated with the replacement, repair, and restoration of injured tissue. Stem cell research is a promising field having maximum therapeutic potential. Cancer stem cells (CSCs) are the cells within the tumor that posses capacity of selfrenewal and have a root cause for the failure of traditional therapies leading to re-occurrence of cancer. CSCs have been identified in blood, breast, brain, and colon cancer. Traditional therapies target only fast growing tumor mass, but not slow-dividing cancer stem cells. It has been shown that embryonic pathways such as Wnt, Hedgehog and Notch, control self-renewal capacity and involved in cancer stem cell maintenance. Targeting of these pathways may be effective in eradicating cancer stem cells and preventing chemotherapy and radiotherapy resistance. Targeting CSCs has become one of the most effective approaches to improve the cancer survival by eradicating the main root cause of cancer. The present review will address, in brief, the importance of cancer stem cells in targeting cancer as better and effective treatment along with a concluding outlook on the scope and challenges in the implication of cancer stem cells in translational oncology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Science.gov (United States)

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. © 2015 AlphaMed Press.

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men.

Science.gov (United States)

Srivastava, Rohit K; Bulte, Jeff W M; Walczak, Piotr; Janowski, Miroslaw

2018-05-01

Neurological disorders are a major threat to public health. Stem cell-based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre-clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000-fold larger volume of the human brain compared to mice. Human GPs transplanted into the mouse brain migrate extensively and can induce global cell replacement, but a similar extent of migration in the human brain would only allow for local rather than global cell replacement. We review here the mechanisms that govern cell migration, which could potentially be exploited to enhance the migratory properties of GPs through cell engineering pre-transplantation. We furthermore discuss the (dis)advantages of the various cell delivery routes that are available, with particular emphasis on intra-arterial injection as the most suitable route for achieving global cell distribution in the larger brain. Now that therapeutic success has proven to be feasible in small animal models, future efforts will need to be directed to enhance global cell delivery and migration to make bench-to-bedside translation a reality. © 2017 Wiley Periodicals, Inc.

Reflective Self-Regenerative Systems Architecture Study

National Research Council Canada - National Science Library

Pu, Carlton; Blough, Douglas

2006-01-01

In this study, we develop the Reflective Self-Regenerative Systems (RSRS) architecture in detail, describing the internal structure of each component and the mutual invocations among the components...

Optimal thermoeconomic performance of an irreversible regenerative ferromagnetic Ericsson refrigeration cycle

International Nuclear Information System (INIS)

Xu, Zhichao; Guo, Juncheng; Lin, Guoxing; Chen, Jincan

2016-01-01

On the basis of the Langevin theory of classical statistical mechanics, the magnetization, entropy, and iso-field heat capacity of ferromagnetic materials are analyzed and their mathematical expressions are derived. An irreversible regenerative Ericsson refrigeration cycle by using a ferromagnetic material as the working substance is established, in which finite heat capacity rates of low and high temperature reservoirs, non-perfect regenerative heat of the refrigeration cycle, additional regenerative heat loss, etc. are taken into account. Based on the regenerative refrigeration cycle model, a thermoeconomic function is introduced as one objective function and optimized with respect to the temperatures of the working substance in the two iso-thermal processes. By means of numerical calculation, the effects of the effective factor of the heat exchangers in high/low temperature reservoir sides, efficiency of the regenerator, heat capacity rate of the low temperature reservoir, and applied magnetic field on the optimal thermoeconomic function as well as the corresponding cooling rate and coefficient of performance are revealed. The results obtained in this paper can provide some theoretical guidance for the optimal design of actual regenerative magnetic refrigerator cycle. - Highlights: • Thermodynamic performance of ferromagnetic material is analyzed. • An irreversible regenerative ferromagnetic Ericsson refrigeration cycle is set up. • The thermoeconomic objective function is introduced and optimized. • Impacts of the thermoeconomic and other parameters are discussed.

Regenerative braking systems with torsional springs made of carbon nanotube yarn

International Nuclear Information System (INIS)

Liu, S; Martin, C; Livermore, C; Lashmore, D; Schauer, M

2014-01-01

The demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as an energy-storing actuator for regenerative braking systems. Originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing until failure. The maximum extractable energy density is measured to be as high as 6.13 kJ/kg. The tests also reveal structural reorganization and hysteresis in the torsional loading curves. A regenerative braking system is built to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yam's twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking system are up to 4.69 kJ/kg and 1.21 kW/kg, respectively. A slightly lower energy density of up to 1.23 kJ/kg and a 0.29 kW/kg mean power density are measured for the CNT yarns in a more complex system that mimics a unidirectional rotating regenerative braking mechanism. The lower energy densities for CNT yarns in the regenerative braking systems as compared with the yarns themselves reflect the frictional losses of the regenerative systems

Regenerative braking systems with torsional springs made of carbon nanotube yarn

Science.gov (United States)

Liu, S.; Martin, C.; Lashmore, D.; Schauer, M.; Livermore, C.

2014-11-01

The demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as an energy-storing actuator for regenerative braking systems. Originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing until failure. The maximum extractable energy density is measured to be as high as 6.13 kJ/kg. The tests also reveal structural reorganization and hysteresis in the torsional loading curves. A regenerative braking system is built to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yam's twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking system are up to 4.69 kJ/kg and 1.21 kW/kg, respectively. A slightly lower energy density of up to 1.23 kJ/kg and a 0.29 kW/kg mean power density are measured for the CNT yarns in a more complex system that mimics a unidirectional rotating regenerative braking mechanism. The lower energy densities for CNT yarns in the regenerative braking systems as compared with the yarns themselves reflect the frictional losses of the regenerative systems.

Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis

Directory of Open Access Journals (Sweden)

Michael G. Poulos

2015-11-01

Full Text Available Hematopoietic stem cells (HSCs inhabit distinct microenvironments within the adult bone marrow (BM, which govern the delicate balance between HSC quiescence, self-renewal, and differentiation. Previous reports have proposed that HSCs localize to the vascular niche, comprised of endothelium and tightly associated perivascular cells. Herein, we examine the capacity of BM endothelial cells (BMECs to support ex vivo and in vivo hematopoiesis. We demonstrate that AKT1-activated BMECs (BMEC-Akt1 have a unique transcription factor/cytokine profile that supports functional HSCs in lieu of complex serum and cytokine supplementation. Additionally, transplantation of BMEC-Akt1 cells enhanced regenerative hematopoiesis following myeloablative irradiation. These data demonstrate that BMEC-Akt1 cultures can be used as a platform for the discovery of pro-HSC factors and justify the utility of BMECs as a cellular therapy. This technical advance may lead to the development of therapies designed to decrease pancytopenias associated with myeloablative regimens used to treat a wide array of disease states.

Regenerative Intelligent Brake Control for Electric Motorcycles

Directory of Open Access Journals (Sweden)

Juan Jesús Castillo Aguilar

2017-10-01

Full Text Available Vehicle models whose propulsion system is based on electric motors are increasing in number within the automobile industry. They will soon become a reliable alternative to vehicles with conventional propulsion systems. The main advantages of this type of vehicles are the non-emission of polluting gases and noise and the effectiveness of electric motors compared to combustion engines. Some of the disadvantages that electric vehicle manufacturers still have to solve are their low autonomy due to inefficient energy storage systems, vehicle cost, which is still too high, and reducing the recharging time. Current regenerative systems in motorcycles are designed with a low fixed maximum regeneration rate in order not to cause the rear wheel to slip when braking with the regenerative brake no matter what the road condition is. These types of systems do not make use of all the available regeneration power, since more importance is placed on safety when braking. An optimized regenerative braking strategy for two-wheeled vehicles is described is this work. This system is designed to recover the maximum energy in braking processes while maintaining the vehicle’s stability. In order to develop the previously described regenerative control, tyre forces, vehicle speed and road adhesion are obtained by means of an estimation algorithm. A based-on-fuzzy-logic algorithm is programmed to carry out an optimized control with this information. This system recuperates maximum braking power without compromising the rear wheel slip and safety. Simulations show that the system optimizes energy regeneration on every surface compared to a constant regeneration strategy.

Characteristics, applications and prospects of mesenchymal stem cells in cell therapy.

Science.gov (United States)

Guadix, Juan A; Zugaza, José L; Gálvez-Martín, Patricia

2017-05-10

Recent advances in the field of cell therapy and regenerative medicine describe mesenchymal stem cells (MSCs) as potential biological products due to their ability to self-renew and differentiate. MSCs are multipotent adult cells with immunomodulatory and regenerative properties, and, given their therapeutic potential, they are being widely studied in order to evaluate their viability, safety and efficacy. In this review, we describe the main characteristics and cellular sources of MSCs, in addition to providing an overview of their properties and current clinical applications, as well offering updated information on the regulatory aspects that define them as somatic cell therapy products. Cell therapy based on MSCs is offered nowadays as a pharmacological alternative, although there are still challenges to be addressed in this regard. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Fuzzy logic electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, Susan R.

1994-01-01

An regenerative antiskid braking and traction control system using fuzzy logic for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensor and determining if regenerative antiskid braking control, requiring hydraulic braking control, and requiring traction control are required. The processor then employs fuzzy logic based on the determined vehicle state and provides command signals to a motor controller to control operation of the electric traction motor and to the brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative braking control, hydraulic braking control, and traction control.

Striated Muscle Function, Regeneration, and Repair

Science.gov (United States)

Shadrin, I.Y.; Khodabukus, A.; Bursac, N.

2016-01-01

As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice. PMID:27271751

Stem Cell Banking for Regenerative and Personalized Medicine

Directory of Open Access Journals (Sweden)

David T. Harris

2014-02-01

Full Text Available 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.

Stem Cell Banking for Regenerative and Personalized Medicine

Science.gov (United States)

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

Improving the Translation of Animal Ischemic Stroke Studies to Humans

OpenAIRE

Jickling, Glen C; Sharp, Frank R

2014-01-01

Despite testing more than 1026 therapeutic strategies in models ischemic stroke and 114 therapies in human ischemic stroke, only one agent tissue plasminogen activator has successfully been translated to clinical practice as a treatment for acute stroke. Though disappointing, this immense body of work has led to a rethinking of animal stroke models and how to better translate therapies to patients with ischemic stroke. Several recommendations have been made, including the STAIR recommendation...

Human resource development contributes to the creation of outstanding regenerative medicine products

Directory of Open Access Journals (Sweden)

Fusako Nishigaki

2017-12-01

Full Text Available Regenerative medicine is currently the focus of global attention. Countries all around the world are actively working to create new regenerative treatment modalities through pioneering research and novel technologies. This is wonderful news for patients who could not be treated with existing medical options. New venture businesses and companies are being established in regenerative medicine and their rapid industrialization is anticipated. However, to ensure high-quality products, human resources qualified in research and development and the manufacturing of these products are essential. The Forum for Innovative Regenerative Medicine (FIRM conducted a questionnaire of its industry members to examine the training and hiring of people in research and development, product creation, manufacturing, and more. Regenerative medicine is a brand new field; thus, many different businesses will need to cooperate together. People with a broad range of technical skills, abilities, and knowledge will be in demand, with various levels of expertise, from basic to advanced.

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.

Science.gov (United States)

Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J; Rafii, Shahin; Ding, Bi-Sen

2017-08-30

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NOX4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 4] synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs ( Hgf iΔEC/iΔEC ) aberrantly up-regulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in Hgf iΔEC/iΔEC mice recapitulated the phenotype of human and mouse liver and lung fibrosis. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Regenerative endodontics as a tissue engineering approach: past, current and future.

Science.gov (United States)

Malhotra, Neeraj; Mala, Kundabala

2012-12-01

With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)(2) in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence-based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth). © 2012 The Authors. Australian Endodontic Journal © 2012 Australian Society of Endodontology.

Bioprinting in Regenerative Medicine

Directory of Open Access Journals (Sweden)

Manuela Monti

2016-02-01

Full Text Available Prof. Turksen is a very well known scientist in the stem cell biology field and he is also internationally known for his fundamental studies on claudin-6. In addition to his research activity he is editor for the Stem Cell Biology and Regenerative Medicine series (Humana Press and editor-in-chief of Stem Cell Reviews and Reports.....

Fuzzy logic electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, S.R.

1994-10-25

An regenerative antiskid braking and traction control system using fuzzy logic for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensor and determining if regenerative antiskid braking control, requiring hydraulic braking control, and requiring traction control are required. The processor then employs fuzzy logic based on the determined vehicle state and provides command signals to a motor controller to control operation of the electric traction motor and to the brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative braking control, hydraulic braking control, and traction control. 123 figs.

Induced pluripotent stem cells for regenerative medicine.

Science.gov (United States)

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.

Stem Cells and Engineered Scaffolds for Regenerative Wound Healing

Directory of Open Access Journals (Sweden)

Biraja C. Dash

2018-03-01

Full Text Available The normal wound healing process involves a well-organized cascade of biological pathways and any failure in this process leads to wounds becoming chronic. Non-healing wounds are a burden on healthcare systems and set to increase with aging population and growing incidences of obesity and diabetes. Stem cell-based therapies have the potential to heal chronic wounds but have so far seen little success in the clinic. Current research has been focused on using polymeric biomaterial systems that can act as a niche for these stem cells to improve their survival and paracrine activity that would eventually promote wound healing. Furthermore, different modification strategies have been developed to improve stem cell survival and differentiation, ultimately promoting regenerative wound healing. This review focuses on advanced polymeric scaffolds that have been used to deliver stem cells and have been tested for their efficiency in preclinical animal models of wounds.

Stem Cells and Engineered Scaffolds for Regenerative Wound Healing.

Science.gov (United States)

Dash, Biraja C; Xu, Zhenzhen; Lin, Lawrence; Koo, Andrew; Ndon, Sifon; Berthiaume, Francois; Dardik, Alan; Hsia, Henry

2018-03-09

The normal wound healing process involves a well-organized cascade of biological pathways and any failure in this process leads to wounds becoming chronic. Non-healing wounds are a burden on healthcare systems and set to increase with aging population and growing incidences of obesity and diabetes. Stem cell-based therapies have the potential to heal chronic wounds but have so far seen little success in the clinic. Current research has been focused on using polymeric biomaterial systems that can act as a niche for these stem cells to improve their survival and paracrine activity that would eventually promote wound healing. Furthermore, different modification strategies have been developed to improve stem cell survival and differentiation, ultimately promoting regenerative wound healing. This review focuses on advanced polymeric scaffolds that have been used to deliver stem cells and have been tested for their efficiency in preclinical animal models of wounds.

Regenerative engineering

CERN Document Server

Laurencin, Cato T

2013-01-01

Regenerative Engineering: The Future of Medicine Saadiq F. El-Amin III , MD , PhD; Joylene W.L. Thomas, MD ; Ugonna N. Ihekweazu, MD ; Mia D. Woods, MS; and Ashim Gupta, MSCell Biology Gloria Gronowicz, PhD and Karen Sagomonyants, DMDStem Cells and Tissue Regeneration Kristen Martins-Taylor, PhD; Xiaofang Wang, MD , PhD; Xue-Jun Li, PhD; and Ren-He Xu, MD , PhDIntroduction to Materials Science Sangamesh G. Kumbar, PhD and Cato T. Laurencin, MD , PhDBiomaterials A. Jon Goldberg, PhD and Liisa T. Kuhn, PhDIn Vitro Assessment of Cell-Biomaterial Interactions Yong Wang, PhDHost Response to Biomate

Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine.

Science.gov (United States)

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.

SPE (tm) regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications

Science.gov (United States)

Mcelroy, J. F.

1990-01-01

Viewgraphs on SPE regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications are presented. Topics covered include: hydrogen-oxygen regenerative fuel cell energy storage system; electrochemical cell reactions; SPE cell voltage stability; passive water removal SPE fuel cell; fuel cell performance; SPE water electrolyzers; hydrophobic oxygen phase separator; hydrophilic/electrochemical hydrogen phase separator; and unitized regenerative fuel cell.

Electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, S.R.

1995-09-12

An antiskid braking and traction control system for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes one or more sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensors and determining if regenerative antiskid braking control, requiring hydraulic braking control, or requiring traction control are required. The processor then employs a control strategy based on the determined vehicle state and provides command signals to a motor controller to control the operation of the electric traction motor and to a brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative antiskid braking control, hydraulic braking control, and traction control. 10 figs.

Electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, Susan R.

1995-01-01

An antiskid braking and traction control system for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes one or more sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensors and determining if regenerative antiskid braking control, requiring hydrualic braking control, or requiring traction control are required. The processor then employs a control strategy based on the determined vehicle state and provides command signals to a motor controller to control the operation of the electric traction motor and to a brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative antiskid braking control, hydraulic braking control, and traction control.

Regenerative strategies for the treatment of knee joint disabilities

CERN Document Server

Reis, Rui

2017-01-01

This book presents regenerative strategies for the treatment of knee joint disabilities. The book is composed of four main sections totaling 19 chapters which review the current knowledge on the clinical management and preclinical regenerative strategies. It examines the role of different natural-based biomaterials as scaffolds and implants for addressing different tissue lesions in the knee joint. Section one provides an updated and comprehensive discussion on articular cartilage tissue regeneration. Section two focuses on the important contributions for bone and osteochondral tissue engineering. Section three overview the recent advances on meniscus repair/regeneration strategies. Finally, section four further discusses the current strategies for treatment of ligament lesions. Each chapter is prepared by world know expert on their fields, so we do firmly believe that the proposed book will be a reference in the area of biomaterials for regenerative medicine.

Radiation Therapy - Multiple Languages

Science.gov (United States)

... W XYZ List of All Topics All Radiation Therapy - Multiple Languages To use the sharing features on this page, ... Information Translations Vietnamese (Tiếng Việt) Expand Section Radiation Therapy - Tiếng Việt (Vietnamese) ... Health Information Translations Characters not displaying correctly on this page? See language display issues . Return to the MedlinePlus Health Information ...

Stem Cells Derived from Amniotic Fluid: A Potential Pluripotent-Like Cell Source for Cellular Therapy?

Science.gov (United States)

Ramasamy, Thamil Selvee; Velaithan, Vithya; Yeow, Yelena; Sarkar, Fazlul H

2018-01-01

Regenerative medicine aims to provide therapeutic treatment for disease or injury, and cell-based therapy is a newer therapeutic approach different from conventional medicine. Ethical issues that rose by the utilisation of human embryonic stem cells (hESC) and the limited capacity of adult stem cells, however, hinder the application of these stem cells in regenerative medicine. Recently, isolation and characterisation of c-kit positive cells from human amniotic fluid, which possess intermediate characteristics between hESCs and adult stem cells, provided a new approach towards realising their promise for fetal and adult regenerative medicine. Despite the number of studies that have been initiated to characterize their molecular signature, research on developing approaches to maintain and enhance their regenerative potential is urgently needed and must be developed. Thus, this review is focused on understanding their potential uses and factors influencing their pluripotent status in vitro. In short, this cell source could be an ideal cellular resource for pluripotent cells for potential applications in allogeneic cellular replacement therapies, fetal tissue engineering, pharmaceutical screening, and in disease modelling. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design and experiment study of a semi-active energy-regenerative suspension system

International Nuclear Information System (INIS)

Shi, Dehua; Chen, Long; Wang, Ruochen; Jiang, Haobin; Shen, Yujie

2015-01-01

A new kind of semi-active energy-regenerative suspension system is proposed to recover suspension vibration energy, as well as to reduce the suspension cost and demands for the motor-rated capacity. The system consists of an energy-regenerative damper and a DC-DC converter-based energy-regenerative circuit. The energy-regenerative damper is composed of an electromagnetic linear motor and an adjustable shock absorber with three regulating levels. The linear motor just works as the generator to harvest the suspension vibration energy. The circuit can be used to improve the system’s energy-regenerative performance and to continuously regulate the motor’s electromagnetic damping force. Therefore, although the motor works as a generator and damps the isolation without an external power source, the motor damping force is controllable. The damping characteristics of the system are studied based on a two degrees of freedom vehicle vibration model. By further analyzing the circuit operation characteristics under different working modes, the double-loop controller is designed to track the desired damping force. The external-loop is a fuzzy controller that offers the desired equivalent damping. The inner-loop controller, on one hand, is used to generate the pulse number and the frequency to control the angle and the rotational speed of the step motor; on the other hand, the inner-loop is used to offer the duty cycle of the energy-regenerative circuit. Simulations and experiments are conducted to validate such a new suspension system. The results show that the semi-active energy-regenerative suspension can improve vehicle ride comfort with the controllable damping characteristics of the linear motor. Meanwhile, it also ensures energy regeneration. (paper)

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

Science.gov (United States)

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.

Embryonic stem cell therapy of heart failure in genetic cardiomyopathy.

Science.gov (United States)

Yamada, Satsuki; Nelson, Timothy J; Crespo-Diaz, Ruben J; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

2008-10-01

Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K(+) (K(ATP)) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional K(ATP) channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is

Regenerative feedback resonant circuit

Science.gov (United States)

Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

2014-09-02

A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

The Ovonic regenerative fuel cell, a fundamentally new approach

International Nuclear Information System (INIS)

Ovshinsky, S.R.; Venkatesan, S.; Corrigan, D.A.

2004-01-01

The Ovonic Regenerative Fuel Cell utilizes Ovonic metal hydride materials in place of traditional noble metal catalysts in the hydrogen fuel electrode. This provides unique features including the ability to capture and utilize regenerative braking energy at high efficiency and the ability to operate for a significant period upon interruption of the hydrogen fuel supply. Additionally, this novel fuel cell does not use high price components, such as platinum catalysts, microporous membranes, and graphite bipolar plates, used in PEM fuel cells. Proof of concept has been demonstrated in full-size multicell prototypes delivering about 100 W power. The Ovonic Regenerative Fuel Cell is yet another component of ECD Ovonic technology contributing to the emerging hydrogen economy which already includes Uni-Solar PV solar cells, Ovonic solid-state hydrogen storage devices, and Ovonic nickel-metal hydride batteries from Cobasys, a joint venture between ECD Ovonics and ChevronTexaco. (author)

Carbon nanotube torsional springs for regenerative braking systems

Science.gov (United States)

Liu, Sanwei; Martin, Corbin; Lashmore, David; Schauer, Mark; Livermore, Carol

2015-10-01

The modeling and demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as energy-storing actuators for regenerative braking systems. An originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing incrementally until failure. The measured average extractable energy density values are 2.9 kJ kg-1  ±  1.2 kJ kg-1 and 3.4 kJ kg-1  ±  0.4 kJ kg-1 for 1-ply CNT yarns and 2-ply CNT yarns, respectively. Additionally, a regenerative braking system is demonstrated to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yarn’s twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking setup are on average 3.3 kJ kg-1 and 0.67 kW kg-1, respectively, with maximum measured values of up to 4.7 kJ kg-1 and 1.2 kW kg-1, respectively. A slightly lower energy density of up to 1.2 kJ kg-1 and a 0.29 kW kg-1 mean power density are measured for CNT yarns in a more complex setup that mimics a unidirectional rotating regenerative braking mechanism.

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

Science.gov (United States)

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

Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

Science.gov (United States)

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.

Recent advances in regenerative medicine to treat enteric neuropathies: use of human cells.

Science.gov (United States)

Stamp, L A; Young, H M

2017-01-01

As current options for treating most enteric neuropathies are either non-effective or associated with significant ongoing problems, cell therapy is a potential attractive possibility to treat congenital and acquired neuropathies. Studies using animal models have shown that following transplantation of enteric neural progenitors into the bowel of recipients, the transplanted cells migrate, proliferate, and generate neurons that are electrically active and receive synaptic inputs. Recent studies have transplanted human enteric neural progenitors into the mouse colon and shown engraftment. In this article, we summarize the significance of these recent advances and discuss priorities for future research that might lead to the use of regenerative medicine to treat enteric neuropathies in the clinic. © 2016 John Wiley & Sons Ltd.

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

Science.gov (United States)

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.

Regenerative Engineering and Bionic Limbs.

Science.gov (United States)

James, Roshan; Laurencin, Cato T

2015-03-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

Advances in using MRI probes and sensors for in vivo cell tracking as applied to regenerative medicine.

Science.gov (United States)

Srivastava, Amit K; Kadayakkara, Deepak K; Bar-Shir, Amnon; Gilad, Assaf A; McMahon, Michael T; Bulte, Jeff W M

2015-04-01

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. © 2015. Published by The Company of Biologists Ltd.

Scaffold translation: barriers between concept and clinic.

Science.gov (United States)

Hollister, Scott J; Murphy, William L

2011-12-01

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges. © Mary Ann Liebert, Inc.

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier

Science.gov (United States)

Tan, Aaron; Chawla, Reema; Natasha, G; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R.; Seifalian, Alexander M.

2015-01-01

Summary The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. PMID:26422652

LOX/Methane Regeneratively-Cooled Rocket Engine Development

Data.gov (United States)

National Aeronautics and Space Administration — The purpose of this project is to advance the technologies required to build a subcritical regeneratively cooled liquid oxygen/methane rocket combustion chamber for...

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

Directory of Open Access Journals (Sweden)

Xiao L

2014-12-01

Full Text Available Li Xiao,1 Masanori Nasu2 1Department of Pharmacology, 2Research Center, The Nippon Dental University, Tokyo, Japan Abstract: 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.Keywords: oral mesenchymal stem cells, oral

[Progress in stem cells and regenerative medicine].

Science.gov (United States)

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.

The imperative for regenerative agriculture.

Science.gov (United States)

Rhodes, Christopher J

2017-03-01

A review is made of the current state of agriculture, emphasising issues of soil erosion and dependence on fossil fuels, in regard to achieving food security for a relentlessly enlarging global population. Soil has been described as "the fragile, living skin of the Earth", and yet both its aliveness and fragility have all too often been ignored in the expansion of agriculture across the face of the globe. Since it is a pivotal component in a global nexus of soil-water-air-energy, how we treat the soil can impact massively on climate change - with either beneficial or detrimental consequences, depending on whether the soil is preserved or degraded. Regenerative agriculture has at its core the intention to improve the health of soil or to restore highly degraded soil, which symbiotically enhances the quality of water, vegetation and land-productivity. By using methods of regenerative agriculture, it is possible not only to increase the amount of soil organic carbon (SOC) in existing soils, but to build new soil. This has the effect of drawing down carbon from the atmosphere, while simultaneously improving soil structure and soil health, soil fertility and crop yields, water retention and aquifer recharge - thus ameliorating both flooding and drought, and also the erosion of further soil, since runoff is reduced. Since food production on a more local scale is found to preserve the soil and its quality, urban food production should be seen as a significant potential contributor to regenerative agriculture in the future, so long as the methods employed are themselves 'regenerative'. If localisation is to become a dominant strategy for dealing with a vastly reduced use of fossil fuels, and preserving soil quality - with increased food production in towns and cities - it will be necessary to incorporate integrated ('systems') design approaches such as permaculture and the circular economy (which minimise and repurpose 'waste') within the existing urban infrastructure. In

Carbon nanotube torsional springs for regenerative braking systems

International Nuclear Information System (INIS)

Liu, Sanwei; Martin, Corbin; Livermore, Carol; Lashmore, David; Schauer, Mark

2015-01-01

The modeling and demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as energy-storing actuators for regenerative braking systems. An originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing incrementally until failure. The measured average extractable energy density values are 2.9 kJ kg −1   ±  1.2 kJ kg −1 and 3.4 kJ kg −1   ±  0.4 kJ kg −1 for 1-ply CNT yarns and 2-ply CNT yarns, respectively. Additionally, a regenerative braking system is demonstrated to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yarn’s twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking setup are on average 3.3 kJ kg −1 and 0.67 kW kg −1 , respectively, with maximum measured values of up to 4.7 kJ kg −1 and 1.2 kW kg −1 , respectively. A slightly lower energy density of up to 1.2 kJ kg −1 and a 0.29 kW kg −1 mean power density are measured for CNT yarns in a more complex setup that mimics a unidirectional rotating regenerative braking mechanism. (paper)

New evaluation methodology of regenerative braking contribution to energy efficiency improvement of electric vehicles

International Nuclear Information System (INIS)

Qiu, Chengqun; Wang, Guolin

2016-01-01

Highlights: • Two different contribution ratio evaluation parameters according to the deceleration braking process are proposed. • Methodologies for calculating the contribution made by regenerative brake to improve vehicle energy efficiency are proposed. • Road test results imply that the proposed parameters are effective. - Abstract: Comprehensive research is conducted on the design and control of a regenerative braking system for electric vehicles. The mechanism and evaluation methods of contribution brought by regenerative braking to improve electric vehicle’s energy efficiency are discussed and analyzed by the energy flow. Methodologies for calculating the contribution made by regenerative brake are proposed. Additionally a new regenerative braking control strategy called “serial 2 control strategy” is introduced. Moreover, two control strategies called “parallel control strategy” and “serial 1 control strategy” are proposed as the comparative control strategy. Furthermore, two different contribution ratio evaluation parameters according to the deceleration braking process are proposed. Finally, road tests are carried out under China typical city regenerative driving cycle standard with three different control strategies. The serial 2 control strategy offers considerably higher regeneration efficiency than the parallel strategy and serial 1 strategy.

Regenerative medicine provides alternative strategies for the treatment of anal incontinence.

Science.gov (United States)

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.

Converging technologies: shaping the future of medicine

Directory of Open Access Journals (Sweden)

Iraj nabipour

2015-01-01

Full Text Available The miniaturization and virtualization processes drive converging technologies from interactions between the NBIC (Nano, Bio, Info, and Cogno technologies. The converging technologies stimulate innovation, promote research and development in different fields and produce revolutionary progresses in medicine. These technologies enable us to create contacts between brains and machines, the growth in molecular nanotechnology, the construction of respirocytes, chromallocytes, clottocytes, nanorobotic phagocytes, and nanobots. Nanobots would enter the nucleus of a cell and extract all of the genetic material and replace it with a synthetically produced copy of the original that has been manufactured in a laboratory to contain only non-defective base-pairs. It is predicted that “the regenerative medicine”, as a megatrend, will have an enormous effect on medical technologies and clinical sciences. Regenerative medicine is an application field of converging technologies in translational medicine. It attempts to translate the results of tissue engineering to construct 3D tissues and organs. Regenerative medicine is also an exciting field for induced pluripotent stem cell (iPSC and promises to bring about a paradigm shift to health care. Accumulating evidence indicates that converging technologies will offer great potentials for regenerative medicine to create innovative treatments for diseases that the traditional therapies have not been effective yet.

Stem Cells and Herbal Acupuncture Therapy

Directory of Open Access Journals (Sweden)

Ki Rok Kwon

2005-12-01

Full Text Available Stem cell therapy implies the birth of regenerative medicine. Regenerative medicine signify treatment through regeneration of cells which was impossible by existing medicine. Stem cell is classified into embryonic stem cell and adult stem cell and they have distinctive benefits and limitations. Researches on stem cell are already under active progression and is expected to be commercially available in the near future. One may not relate the stem cell treatment with Oriental medicine, but can be interpreted as the fundamental treatment action of Oriental medicine is being investigated in more concrete manner. When it comes to difficult to cure diseases, there is no boundary between eastern and western medicine, and one must be ready to face and overcome changes lying ahead.

Vibration control of an energy regenerative seat suspension with variable external resistance

Science.gov (United States)

Ning, Donghong; Sun, Shuaishuai; Du, Haiping; Li, Weihua; Zhang, Nong

2018-06-01

In this paper, an energy regenerative seat suspension with a variable external resistance is proposed and built, and a semi-active controller for its vibration control is also designed and validated. The energy regenerative seat suspension is built with a three-phase generator and a gear reducer, which are installed in the scissors structure centre of the seat suspension, and the vibration energy is directly harvested from the rotary movement of suspension's scissors structure. The electromagnetic torque of the semi-active seat suspension actuator is controlled by an external variable resistor. An integrated model including the seat suspension's kinematics and the generator is built and proven to match the test result very well. A simplified experimental phenomenon model is also built based on the test results for the controller design. A state feedback H∞ controller is proposed for the regenerative seat suspension's semi-active vibration control. The proposed regenerative seat suspension and its controller are validated with both simulations and experiments. A well-tuned passive seat suspension is applied to evaluate the regenerative seat's performance. Based on ISO 2631-1, the frequency-weighted root mean square (FW-RMS) acceleration of the proposed seat suspension has a 22.84% reduction when compared with the passive one, which indicates the improvement of ride comfort. At the same time, the generated RMS power is 1.21 W. The proposed regenerative seat suspension can greatly improve the driver's ride comfort and has the potential to be developed to a self-powered semi-active system.

Mechanical cues in orofacial tissue engineering and regenerative medicine.

Science.gov (United States)

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.

Regenerative memory in time-delayed neuromorphic photonic resonators

Science.gov (United States)

Romeira, B.; Avó, R.; Figueiredo, José M. L.; Barland, S.; Javaloyes, J.

2016-01-01

We investigate a photonic regenerative memory based upon a neuromorphic oscillator with a delayed self-feedback (autaptic) connection. We disclose the existence of a unique temporal response characteristic of localized structures enabling an ideal support for bits in an optical buffer memory for storage and reshaping of data information. We link our experimental implementation, based upon a nanoscale nonlinear resonant tunneling diode driving a laser, to the paradigm of neuronal activity, the FitzHugh-Nagumo model with delayed feedback. This proof-of-concept photonic regenerative memory might constitute a building block for a new class of neuron-inspired photonic memories that can handle high bit-rate optical signals.

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier.

Science.gov (United States)

Tan, Aaron; Chawla, Reema; G, Natasha; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R; Seifalian, Alexander M

2016-01-01

The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

Challenges and rewards on the road to translational systems biology in acute illness: four case reports from interdisciplinary teams.

Science.gov (United States)

An, Gary; Hunt, C Anthony; Clermont, Gilles; Neugebauer, Edmund; Vodovotz, Yoram

2007-06-01

Translational systems biology approaches can be distinguished from mainstream systems biology in that their goal is to drive novel therapies and streamline clinical trials in critical illness. One systems biology approach, dynamic mathematical modeling (DMM), is increasingly used in dealing with the complexity of the inflammatory response and organ dysfunction. The use of DMM often requires a broadening of research methods and a multidisciplinary team approach that includes bioscientists, mathematicians, engineers, and computer scientists. However, the development of these groups must overcome domain-specific barriers to communication and understanding. We present 4 case studies of successful translational, interdisciplinary systems biology efforts, which differ by organizational level from an individual to an entire research community. Case 1 is a single investigator involved in DMM of the acute inflammatory response at Cook County Hospital, in which extensive translational progress was made using agent-based models of inflammation and organ damage. Case 2 is a community-level effort from the University of Witten-Herdecke in Cologne, whose efforts have led to the formation of the Society for Complexity in Acute Illness. Case 3 is an institution-based group, the Biosystems Group at the University of California, San Francisco, whose work has included a focus on a common lexicon for DMM. Case 4 is an institution-based, transdisciplinary research group (the Center for Inflammation and Regenerative Modeling at the University of Pittsburgh), whose modeling work has led to internal education efforts, grant support, and commercialization. A transdisciplinary approach, which involves team interaction in an iterative fashion to address ambiguity and is supported by educational initiatives, is likely to be necessary for DMM in acute illness. Communitywide organizations such as the Society of Complexity in Acute Illness must strive to facilitate the implementation of DMM in

Stem Cell Tracking Technologies for Neurological Regenerative Medicine Purposes

Directory of Open Access Journals (Sweden)

Yongtao Zheng

2017-01-01

Full Text Available The growing field of stem cell therapy is moving toward clinical trials in a variety of applications, particularly for neurological diseases. However, this translation of cell therapies into humans has prompted a need to create innovative and breakthrough methods for stem cell tracing, to explore the migration routes and its reciprocity with microenvironment targets in the body, to monitor and track the outcome after stem cell transplantation therapy, and to track the distribution and cell viability of transplanted cells noninvasively and longitudinally. Recently, a larger number of cell tracking methods in vivo were developed and applied in animals and humans, including magnetic resonance imaging, nuclear medicine imaging, and optical imaging. This review has been intended to summarize the current use of those imaging tools in tracking stem cells, detailing their main features and drawbacks, including image resolution, tissue penetrating depth, and biosafety aspects. Finally, we address that multimodality imaging method will be a more potential tracking tool in the future clinical application.

Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

Science.gov (United States)

Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

Translation of the Speech Therapy Programs in the Logomon Assisted Therapy System

Directory of Open Access Journals (Sweden)

SCHIPOR, D. M.

2010-05-01

Full Text Available This interdisciplinary research was developed with a view to create and implement an intelligent informatics system for the treatment of dyslalic disorders, specific to the Romanian language (CBTS system - computer-based speech therapy, as a complementary speech therapy method, customised and client-oriented. The rules of the logotherapeutic guide have been expressed in pseudocode programs in order to allow a greater flexibility in expressing the logotherapeutic procedures in an informatics system. The pseudocode logopedic programs comprise the succession of stages of the therapeutic program from a speech therapy perspective, and based on what the expert system can achieve. The LOGOMON system is conceived in order to assist the physical therapist and the child during the entire therapeutic period, recording the main data related to the child, which proved to be useful in diagnosis and treatment. The experimental validation of the system proved that assisted therapy contributes to the improvement of classical therapy, to obtaining optimal results in correcting the dyslalic person's speech.

Advanced regenerative heat recovery system

Science.gov (United States)

Prasad, A.; Jasti, J. K.

1982-02-01

A regenerative heat recovery system was designed and fabricated to deliver 1500 scfm preheated air to a maximum temperature of 1600 F. Since this system is operating at 2000 F, the internal parts were designed to be fabricated with ceramic materials. This system is also designed to be adaptable to an internal metallic structure to operate in the range of 1100 to 1500 F. A test facility was designed and fabricated to test this system. The test facility is equipped to impose a pressure differential of up to 27 inches of water column in between preheated air and flue gas lines for checking possible leakage through the seals. The preliminary tests conducted on the advanced regenerative heat recovery system indicate the thermal effectiveness in the range of 60% to 70%. Bench scale studies were conducted on various ceramic and gasket materials to identify the proper material to be used in high temperature applications. A market survey was conducted to identify the application areas for this heat recovery system. A cost/benefit analysis showed a payback period of less than one and a half years.

Nonlinear Modeling and Coordinate Optimization of a Semi-Active Energy Regenerative Suspension with an Electro-Hydraulic Actuator

Directory of Open Access Journals (Sweden)

Farong Kou

2018-01-01

Full Text Available In order to coordinate the damping performance and energy regenerative performance of energy regenerative suspension, this paper proposes a structure of a vehicle semi-active energy regenerative suspension with an electro-hydraulic actuator (EHA. In light of the proposed concept, a specific energy regenerative scheme is designed and a mechanical properties test is carried out. Based on the test results, the parameter identification for the system model is conducted using a recursive least squares algorithm. On the basis of the system principle, the nonlinear model of the semi-active energy regenerative suspension with an EHA is built. Meanwhile, linear-quadratic-Gaussian control strategy of the system is designed. Then, the influence of the main parameters of the EHA on the damping performance and energy regenerative performance of the suspension is analyzed. Finally, the main parameters of the EHA are optimized via the genetic algorithm. The test results show that when a sinusoidal is input at the frequency of 2 Hz and the amplitude of 30 mm, the spring mass acceleration root meam square value of the optimized EHA semi-active energy regenerative suspension is reduced by 22.23% and the energy regenerative power RMS value is increased by 40.51%, which means that while meeting the requirements of vehicle ride comfort and driving safety, the energy regenerative performance is improved significantly.

Thermo-economic optimization of Regenerative Organic Rankine Cycle for waste heat recovery applications

International Nuclear Information System (INIS)

Imran, Muhammad; Park, Byung Sik; Kim, Hyouck Ju; Lee, Dong Hyun; Usman, Muhammad; Heo, Manki

2014-01-01

Highlights: • Thermo-economic optimization of regenerative ORC is performed. • Optimization is performed using multi objective genetic algorithm. • Objective function is maximum cycle efficiency and minimum specific investment. • Evaporation pressure, pinch point and superheat are decision variables. • Sensitivity analysis is performed to investigate effect of decision variables. - Abstract: Organic Rankine Cycle (ORC) is low grade and waste heat conversion technology. The current article deal with the thermo-economic optimization of basic ORC and regenerative ORC for waste heat recovery applications under constant heat source condition. Thermal efficiency and specific investment cost of basic ORC, single stage regenerative and double stage regenerative ORC has been optimized by using Non-dominated Sorting Genetic Algorithm-II (NSGA-II). Maximum thermal efficiency and minimum specific investment cost were selected as objective functions and relative increase in thermal efficiency and cost has been analyzed taking the basic ORC as base case. The constraint set consist of evaporation pressure, superheat, pinch point temperature difference in evaporator and condenser. The optimization was performed for five different working fluids. The optimization result show that R245fa is best working under considered conditions and basic ORC has low specific investment cost and thermal efficiency compared to regenerative ORC. R245fa is low boiling organic fluid, which has high degree of thermal stability and compatible with common construction materials of ORC. The average increase in thermal efficiency from basic ORC to single stage regenerative ORC was 1.01% with an additional cost of 187 $/kW while from basic ORC to double stage regenerative ORC was 1.45% with an average increase in cost of 297 $/kW. The sensitivity analysis was also performed to investigate the effect of operating conditions which show that evaporation pressure has promising effect on thermal

Device for processing regenerative wastes of ion exchange resin

International Nuclear Information System (INIS)

Kuroda, Osamu; Ebara, Katsuya; Shindo, Toshikazu; Takahashi, Sankichi

1986-01-01

Purpose: To facilitate the operation and maintenance of a processing device by dividing radioactive wastes produced in the regenerative process of ion exchange resin into a regenerated usable recovery liquid and wastes. Constitution: Sulfuric acid is recovered by a diffusion dialysis method from wastes containing sulfuric acid that are generated in the regenerative process of cation-exchange resin and also caustic soda is recovered by the diffusion dialysis method from wastes containing caustic soda that are generated in the regenerative process of anion-exchange resin. The sulfuric acid and caustic soda thus recovered are used for the regeneration of ion-exchange resin. A concentrator is provided for concentrating the sulfuric acid and caustic soda water solution to concentration suitable for the regeneration of these ion-exchange resins. Also provided is a recovery device for recovering water generated from the concentrator. This device is of so simple a constitution that its operation and maintenance can be performed very easily, thereby greatly reducing the quantity of waste liquid required to be stored in drums. (Takahashi, M.)

Regenerative Medicine Applications in Wound Care.

Science.gov (United States)

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

2017-01-01

During the last two decades, a number of studies have been carried out on the application of regenerative medicine in the field of dermatology. The aim of this research was to critically review the application of regenerative medicine in the field of dermatology. The next aim was to look in depth to see whether regenerative medicine strategies have a place in the future of wound healing in a clinical setting. More specifically, to see if these strategies would apply for burns and non-healing diabetic wounds. Billions of dollars have been spent worldwide on research in wound treatment and skin regeneration. Although a high number of clinical trials show promising results, there is still no commercially available treatment for use. In addition, the outcome data from the clinical trials, taking place throughout the world, are not published in a standardized manner. Standardization within clinical trials is required for: protocols, outcome, endpoint values, and length of follow-up. The lack of standardization makes it much more difficult to compare the data collected and the different types of treatment. Despite several promising results from research and early phase clinical studies, the treatment for wounds as well as skin regeneration is still considered as an unmet clinical need. However, in the past three years, more promising research has been approaching clinical trials; this could be the solution that clinicians have been waiting for. This is a multibillion dollar industry for which there should be enough incentive for researchers and industry to seek the solution. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adipose-derived mesenchymal stem cells and regenerative medicine.

Science.gov (United States)

Konno, Masamitsu; Hamabe, Atsushi; Hasegawa, Shinichiro; Ogawa, Hisataka; Fukusumi, Takahito; Nishikawa, Shimpei; Ohta, Katsuya; Kano, Yoshihiro; Ozaki, Miyuki; Noguchi, Yuko; Sakai, Daisuke; Kudoh, Toshihiro; Kawamoto, Koichi; Eguchi, Hidetoshi; Satoh, Taroh; Tanemura, Masahiro; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

2013-04-01

Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Regenerative Endodontic Treatment of a Maxillary Mature Premolar

Directory of Open Access Journals (Sweden)

Qingan Xu

2018-01-01

Full Text Available Regenerative endodontic treatment was performed on a mature maxillary premolar diagnosed as chronic pulpitis. The root canals were chemomechanically prepared and placed intracanal medicaments at the first appointment. Then 2 weeks later, a blood clot was created in the canals, over which mineral trioxide aggregate was placed. At 6-month follow-up, cementum-like tissue seemed to be formed in the root canal along with nearly recovered pulp vitality. At 12-month recall, the radiographic results revealed evidence of root wall thickening. At 30-month recall, no periapical lesion was found. This case report indicates that regenerative endodontic treatment for the mature premolar is feasible. More cases are needed for further validation.

NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.

Science.gov (United States)

Palmieri, C; Cleator, S; Kilburn, L S; Kim, S B; Ahn, S-H; Beresford, M; Gong, G; Mansi, J; Mallon, E; Reed, S; Mousa, K; Fallowfield, L; Cheang, M; Morden, J; Page, K; Guttery, D S; Rghebi, B; Primrose, L; Shaw, J A; Thompson, A M; Bliss, J M; Coombes, R C

2014-12-01

Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE₁₀₀C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

Maximum Safety Regenerative Power Tracking for DC Traction Power Systems

Directory of Open Access Journals (Sweden)

Guifu Du

2017-02-01

Full Text Available Direct current (DC traction power systems are widely used in metro transport systems, with running rails usually being used as return conductors. When traction current flows through the running rails, a potential voltage known as “rail potential” is generated between the rails and ground. Currently, abnormal rises of rail potential exist in many railway lines during the operation of railway systems. Excessively high rail potentials pose a threat to human life and to devices connected to the rails. In this paper, the effect of regenerative power distribution on rail potential is analyzed. Maximum safety regenerative power tracking is proposed for the control of maximum absolute rail potential and energy consumption during the operation of DC traction power systems. The dwell time of multiple trains at each station and the trigger voltage of the regenerative energy absorbing device (READ are optimized based on an improved particle swarm optimization (PSO algorithm to manage the distribution of regenerative power. In this way, the maximum absolute rail potential and energy consumption of DC traction power systems can be reduced. The operation data of Guangzhou Metro Line 2 are used in the simulations, and the results show that the scheme can reduce the maximum absolute rail potential and energy consumption effectively and guarantee the safety in energy saving of DC traction power systems.

Developing translational medicine professionals : The Marie Skłodowska-Curie action model

NARCIS (Netherlands)

Petrelli, Alessandra; Prakken, Berent J.; Rosenblum, Norman D.

2016-01-01

End goal of translational medicine is to combine disciplines and expertise to eventually promote improvement of the global healthcare system by delivering effective therapies to individuals and society. Well-trained experts of the translational medicine process endowed with profound knowledge of

Cell Therapy in Dermatology

Science.gov (United States)

Petrof, Gabriela; Abdul-Wahab, Alya; McGrath, John A.

2014-01-01

Harnessing the regenerative capacity of keratinocytes and fibroblasts from human skin has created new opportunities to develop cell-based therapies for patients. Cultured cells and bioengineered skin products are being used to treat patients with inherited and acquired skin disorders associated with defective skin, and further clinical trials of new products are in progress. The capacity of extracutaneous sources of cells such as bone marrow is also being investigated for its plasticity in regenerating skin, and new strategies, such as the derivation of inducible pluripotent stem cells, also hold great promise for future cell therapies in dermatology. This article reviews some of the preclinical and clinical studies and future directions relating to cell therapy in dermatology, particularly for inherited skin diseases associated with fragile skin and poor wound healing. PMID:24890834

An animal model to study regenerative endodontics.

Science.gov (United States)

Torabinejad, Mahmoud; Corr, Robert; Buhrley, Matthew; Wright, Kenneth; Shabahang, Shahrokh

2011-02-01

A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days. Copyright © 2011. Published by Elsevier Inc.

Regenerative surgical therapy for peri-implantitis using deproteinized bovine bone mineral with 10% collagen, enamel matrix derivative and Doxycycline-A prospective 3-year cohort study.

Science.gov (United States)

Mercado, Faustino; Hamlet, Stephen; Ivanovski, Saso

2018-05-16

There is limited evidence regarding the long-term efficacy of regenerative treatment for peri-implantitis. The aim of this study was to evaluate a combination therapy of deproteinized bovine bone mineral with 10% collagen (DBBMC), enamel matrix derivative (EMD) and Doxycycline in the regeneration of bone defects associated with peri-implantitis. Thirty patients diagnosed with peri-implantitis (BoP/suppuration, probing depth greater than 4 mm, minimum radiographic bone loss of 20%, at least 2 years in function) were enrolled in the study. Clinical measurements included probing depths, recession, radiographic bone fill, gingival inflammation and bleeding on probing/suppuration. Following surgical access and debridement, the implant surfaces were decontaminated with 24% EDTA for 2 min, and the bone defects were filled with a combined mixture of DBBMC, EMD and Doxycycline powder. The defects were covered with connective tissue grafts where necessary. Clinical measurements were recorded after 12, 24 and 36 months. The mean probing depth and bone loss at the initial visit was 8.9 mm (±1.9) and 6.92 mm (±1.26), respectively. Both mean probing depth and bone loss reduced significantly from baseline to 3.55 mm (±0.50) and 2.85 mm (±0.73) at 12 months, 3.50 (±0.50) and 2.62 mm (±0.80) at 24 months and 3.50 mm (±0.50) and 2.60 mm (±0.73) at 36 months. 56.6% of the implants were considered successfully treated (according to Successful Treatment Outcome Criterion: PD 10%, no BoP/suppuration, no recession >0.5 mm for anterior implants and >1.5 mm for posterior implants) after 36 months. Regenerative treatment of peri-implantitis using a combined mixture of DBBMC, EMD and Doxycycline achieved promising results. The benefits of this protocol incorporating EMD should be tested in randomized clinical trials. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regenerative laser system

International Nuclear Information System (INIS)

Biancardi, F.R.; Landerman, A.; Melikian, G.

1975-01-01

Regenerative apparatus for exhausting the working medium from the optical cavity of a laser and for supplying preheated diluent to the reaction chamber of a laser is disclosed. In an aftercooler thermal energy is exchanged between the working medium exhausted from the optical cavity and a cryogenic coolant which is subsequently utilized as the motive fluid for an ejector and as a diluent in the production of laser gas. Highly toxic and corrosive gases are condensed out of the working medium as the cryogenic coolant is evaporated and superheated. A preheater transfers additional heat to the diluent before the diluent enters the reaction chamber. (U.S.)

Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report

International Nuclear Information System (INIS)

Portas, M.; Coppola, A.; Mansilla, E.; Drago, H.; Dubner, D.; Radl, A.; Di Giorgio, M.

2016-01-01

Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial micro-vessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radio-pathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radio-pathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy. (authors)

Design control for clinical translation of 3D printed modular scaffolds.

Science.gov (United States)

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach

Stem cells and the future of regenerative medicine

National Research Council Canada - National Science Library

National Research Council, Committee on the Biological and Biomedical Applications of Stem Cell Research; Commission on Life Sciences; National Research Council; Board on Life Sciences; Board on Neuroscience and Behavioral Health; Division on Earth and Life Studies; Institute of Medicine

2002-01-01

.... Stem Cells and the Future of Regenerative Medicine provides a deeper exploration of the biological, ethical, and funding questions prompted by the therapeutic potential of undifferentiated human cells...

The Impact of Machine Translation and Computer-aided Translation on Translators

Science.gov (United States)

Peng, Hao

2018-03-01

Under the context of globalization, communications between countries and cultures are becoming increasingly frequent, which make it imperative to use some techniques to help translate. This paper is to explore the influence of computer-aided translation on translators, which is derived from the field of the computer-aided translation (CAT) and machine translation (MT). Followed by an introduction to the development of machine and computer-aided translation, it then depicts the technologies practicable to translators, which are trying to analyze the demand of designing the computer-aided translation so far in translation practice, and optimize the designation of computer-aided translation techniques, and analyze its operability in translation. The findings underline the advantages and disadvantages of MT and CAT tools, and the serviceability and future development of MT and CAT technologies. Finally, this thesis probes into the impact of these new technologies on translators in hope that more translators and translation researchers can learn to use such tools to improve their productivity.

Optimization of the alignment sensitivity and energy stability of the NIF regenerative amplifier cavity

International Nuclear Information System (INIS)

Hopps, N. W.

1998-01-01

The work to improve the energy stability of the regenerative amplifier ('regen') for the National Ignition Facility is described. This includes a fast feed-forward system, designed to regulate the output energy of the regen by monitoring how quickly a pulse builds up over many round trips. Shot-to-shot energy fluctuations of all elements prior to (and including) the regen may be compensated for in this way, at the expense of a loss of approximately 50%. Also included is a detailed study into the alignment sensitivity of the regen cavity, with the goal of quantifying the effect of misalignment on the output energy. This is done by calculating the displacement of the eigenmode by augmenting the cavity ABCD matrix with the misalignment matrix elements, E, F. In this way, cavity misalignment issues due to thermal loading of the gain medium are investigated. Alternative cavity designs, which reduce the alignment sensitivity and therefore the energy drift over periods of continuous operation, are considered. Alterations to the amplifier head design are also considered

Adaptation and validation of the REGEN expert system for the Central Appalachians

Science.gov (United States)

Lance A. Vickers; Thomas R. Fox; David L. Loftis; David A. Boucugnani

2011-01-01

REGEN is an expert system that predicts future species composition at the onset of stem exclusion using preharvest stand conditions. To extend coverage into hardwood stands of the Central Appalachians, we developed REGEN knowledge bases for four site qualities (xeric, subxeric, submesic, mesic) based on relevant literature and expert opinion. Data were collected from...

Predicting Forest Regeneration in the Central Appalachians Using the REGEN Expert System

Science.gov (United States)

Lance A. Vickers; Thomas R. Fox; David L. Loftis; David A. Boucugnani

2011-01-01

REGEN is an expert system designed by David Loftis to predict the future species composition of dominant and codominant stems in forest stands at the onset of stem exclusion following a proposed harvest. REGEN predictions are generated using competitive rankings for advance reproduction along with other existing stand conditions. These parameters are contained within...

Enhanced Regenerative Braking Strategies for Electric Vehicles: Dynamic Performance and Potential Analysis

Directory of Open Access Journals (Sweden)

Boyi Xiao

2017-11-01

Full Text Available A regenerative braking system and hydraulic braking system are used in conjunction in the majority of electric vehicles worldwide. We propose a new regenerative braking distribution strategy that is based on multi-input fuzzy control logic while considering the influences of the battery’s state of charge, the brake strength and the motor speed. To verify the braking performance and recovery economy, this strategy was applied to a battery electric vehicle model and compared with two other improved regenerative braking strategies. The performance simulation was performed using standard driving cycles (NEDC, LA92, and JP1015 and a real-world-based urban cycle in China. The tested braking strategies satisfied the general safety requirements of Europe (as specified in ECE-13H, and the emergency braking scenario and economic potential were tested. The simulation results demonstrated the differences in the braking force distribution performance of these three regenerative braking strategies, the feasibility of the braking methods for the proposed driving cycles and the energy economic potential of the three strategies.

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine.

Science.gov (United States)

Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C; Nolta, Jan A; Athanasiou, Kyriacos A

2015-10-01

analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use. ©AlphaMed Press.

Regenerative endodontics: a true paradigm shift or a bandwagon about to be derailed?

Science.gov (United States)

Nazzal, H; Duggal, M S

2017-02-01

Regenerative endodontic techniques (RETs) have been hailed as a paradigm shift for the management of traumatised non-vital immature permanent anterior teeth. In this article the aim was to critically appraise the literature with regards to the outcome of regenerative endodontics on root development. Critical review of the literature where regenerative endodontic techniques have been used in the management of immature non-vital teeth with continuation of root development as the main outcome reported. Most studies published were in the form of case reports and series with very few randomised controlled trials with a high risk of bias. Continuation of root development following the use of RET has been shown to be unpredictable at best with lower success in those teeth losing vitality as a result of dental trauma. Despite the high success of regenerative endodontics in terms of periodontal healing including resolution of clinical and radiographic signs and symptoms of infection, continuation of root development remains an unpredictable outcome. The use of a blood clot as a scaffold in regenerative endodontics should be reviewed carefully as that might offer an environment for repair rather than regeneration. In addition, preservation of structures, such as Hertwig's epithelial root sheath, may have an important bearing on the success of this approach and should be further investigated.

Use of Tablet Computers to Promote Physical Therapy Students' Engagement in Knowledge Translation During Clinical Experiences

Science.gov (United States)

Loeb, Kathryn; Barbosa, Sabrina; Jiang, Fei; Lee, Karin T.

2016-01-01

Background and Purpose: Physical therapists strive to integrate research into daily practice. The tablet computer is a potentially transformational tool for accessing information within the clinical practice environment. The purpose of this study was to measure and describe patterns of tablet computer use among physical therapy students during clinical rotation experiences. Methods: Doctor of physical therapy students (n = 13 users) tracked their use of tablet computers (iPad), loaded with commercially available apps, during 16 clinical experiences (6-16 weeks in duration). Results: The tablets were used on 70% of 691 clinic days, averaging 1.3 uses per day. Information seeking represented 48% of uses; 33% of those were foreground searches for research articles and syntheses and 66% were for background medical information. Other common uses included patient education (19%), medical record documentation (13%), and professional communication (9%). The most frequently used app was Safari, the preloaded web browser (representing 281 [36.5%] incidents of use). Users accessed 56 total apps to support clinical practice. Discussion and Conclusions: Physical therapy students successfully integrated use of a tablet computer into their clinical experiences including regular activities of information seeking. Our findings suggest that the tablet computer represents a potentially transformational tool for promoting knowledge translation in the clinical practice environment. Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A127). PMID:26945431

Translation Theory 'Translated'

DEFF Research Database (Denmark)

Wæraas, Arild; Nielsen, Jeppe

2016-01-01

Translation theory has proved to be a versatile analytical lens used by scholars working from different traditions. On the basis of a systematic literature review, this study adds to our understanding of the ‘translations’ of translation theory by identifying the distinguishing features of the most...... common theoretical approaches to translation within the organization and management discipline: actor-network theory, knowledge-based theory, and Scandinavian institutionalism. Although each of these approaches already has borne much fruit in research, the literature is diverse and somewhat fragmented......, but also overlapping. We discuss the ways in which the three versions of translation theory may be combined and enrich each other so as to inform future research, thereby offering a more complete understanding of translation in and across organizational settings....

Binary translation using peephole translation rules

Science.gov (United States)

Bansal, Sorav; Aiken, Alex

2010-05-04

An efficient binary translator uses peephole translation rules to directly translate executable code from one instruction set to another. In a preferred embodiment, the translation rules are generated using superoptimization techniques that enable the translator to automatically learn translation rules for translating code from the source to target instruction set architecture.

Nanotechnologies in regenerative medicine

Czech Academy of Sciences Publication Activity Database

Kubinová, Šárka; Syková, Eva

2010-01-01

Roč. 19, 3-4 (2010), s. 144-156 ISSN 1364-5706 R&D Projects: GA AV ČR IAA500390902; GA MŠk(CZ) LC554; GA AV ČR KAN201110651 Grant - others:GA ČR(CZ) 1M0538; GA ČR(CZ) GA203/09/1242; GA AV ČR(CZ) KAN200520804; EC FP6 project ENIMET(XE) LSHM-CT-2005-019063 Program:1M; GA; KA Institutional research plan: CEZ:AV0Z50390703 Keywords : Nanotechnology * regenerative medicine * nanofibers Subject RIV: FH - Neurology Impact factor: 1.051, year: 2010

Regenerative medicine in Europe: global competition and innovation governance.

Science.gov (United States)

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.

Liability versus innovation: the legal case for regenerative medicine.

Science.gov (United States)

Keren-Paz, Tsachi; El Haj, Alicia J

2014-10-01

Medical innovation occupies a position somewhere between standard practice and clinical research, but innovation is primarily intended to benefit an individual patient where standard treatment fails. Medical innovations in the area of regenerative medicine have the potential to completely transform medical practice, but rely upon some major revision to the nature of treatments beyond drug-based therapies. There is considerable investment in scientific and clinical research, but further attention could be paid to legal barriers to medical innovation imposed by the threat of medical malpractice. We survey in this article the legal framework for making determinations of medical malpractice in general, and highlight the issues specific to innovative treatments. In essence, liability could be imposed for failing to adequately inform the patient about the innovative nature of the suggested therapy or based on the fact that the risks outweighed the benefits. As for the latter, we examine whether liability is likely to be based merely on deviating from existing practice or on an examination on the merits of the treatments' risks and benefits. The facts that some risks are unforeseeable and some benefits are external to the patient complicate negligence determinations. The first fact relates to the problem of judging adverse events in hindsight; the second, to the obligation to make decisions based on the patient's best interest and avoid conflict of interests. In addition, we evaluate the relationship between the obligations to secure the patient's informed consent and to avoid clinical negligence. We identify the need for further research to examine the significance of the putative anti-innovation bias that current liability regimen has, and to examine whether a move to strict liability might avoid such bias, while being fair to patients who contribute for the advancement of medical knowledge by participating in innovative therapies.

Regenerative Snubber For GTO-Commutated SCR Inverter

Science.gov (United States)

Rippel, Wally E.; Edwards, Dean B.

1992-01-01

Proposed regenerative snubbing circuit substituted for dissipative snubbing circuit in inverter based on silicon controlled rectifiers (SCR's) commutated by gate-turn-off thyristor (GTO). Intended to reduce loss of power that occurs in dissipative snubber. Principal criteria in design: low cost, simplicity, and reliability.

On friction braking demand with regenerative braking

NARCIS (Netherlands)

Walker, A.M.; Lampérth, M.U.; Wilkins, S.

2002-01-01

Developments in Hybrid Electric and pure Electric Vehicles are intended to improve the operational efficiency of road vehicles. Regenerative braking, which has long been established in rail vehicles, is integral to efficiency improvement, with up to 30% of overall traction energy demand satisfied by

A novel regenerative shock absorber with a speed doubling mechanism and its Monte Carlo simulation

Science.gov (United States)

Zhang, Ran; Wang, Xu; Liu, Zhenwei

2018-03-01

A novel regenerative shock absorber has been designed and fabricated. The novelty of the presented work is the application of the double speed regenerative shock absorber that utilizes the rack and pinion mechanism to increase the magnet speed with respect to the coils for higher power output. The simulation models with parameters identified from finite element analysis and the experiments are developed. The proposed regenerative shock absorber is compared with the regenerative shock absorber without the rack and pinion mechanism, when they are integrated into the same quarter vehicle suspension system. The sinusoidal wave road profile displacement excitation and the random road profile displacement excitation with peak amplitude of 0.035 m are applied as the inputs in the frequency range of 0-25 Hz. It is found that with the sinusoidal and random road profile displacement input, the proposed innovative design can increase the output power by 4 times comparing to the baseline design. The proposed double speed regenerative shock absorber also presents to be more sensitive to the road profile irregularity than the single speed regenerative shock absorber as suggested by Monte Carlo simulation. Lastly the coil mass and amplification factor are studied for sensitivity analysis and performance optimization, which provides a general design method of the regenerative shock absorbers. It shows that for the system power output, the proposed design becomes more sensitive to either the coil mass or amplification factor depending on the amount of the coil mass. With the specifically selected combination of the coil mass and amplification factor, the optimized energy harvesting performance can be achieved.

Artificial organs versus regenerative medicine: is it true?

Science.gov (United States)

Nosé, Yukihiko; Okubo, Hisashi

2003-09-01

Individuals engaged in the fields of artificial kidney and artificial heart have often mistakenly stated that "the era of artificial organs is over; regenerative medicine is the future." Contrarily, we do not believe artificial organs and regenerative medicine are different medical technologies. As a matter of fact, artificial organs developed during the last 50 years have been used as a bridge to regeneration. The only difference between regenerative medicine and artificial organs is that artificial organs for the bridge to regeneration promote tissue regeneration in situ, instead of outside the body (for example, vascular prostheses, neuroprostheses, bladder substitutes, skin prostheses, bone prostheses, cartilage prostheses, ligament prostheses, etc.). All of these artificial organs are successful because tissue regeneration over a man-made prosthesis is established inside the patient's body (artificial organs to support regeneration). Another usage of the group of artificial organs for the bridge to regeneration is to sustain the functions of the patient's diseased organs during the regeneration process of the body's healthy tissues and/or organs. This particular group includes artificial kidney, hepatic assist, respiratory assist, and circulatory assist. Proof of regeneration of these healthy tissues and/or organs is demonstrated in the short-term recovery of end-stage organ failure patients (artificial organs for bridge to regeneration). A third group of artificial organs for the bridge to regeneration accelerates the regenerating process of the patient's healthy tissues and organs. This group includes neurostimulators, artificial blood (red cells) blood oxygenators, and plasmapheresis devices, including hemodiafiltrators. So-called "therapeutic artificial organs" fall into this category (artificial organs to accelerate regeneration). Thus, almost all of today's artificial organs are useful in the bridge to regeneration of healthy natural tissues and organs

Resolution of temporomandibular joint dysfunction (TMJD) by correcting a lateral head translation posture following previous failed traditional chiropractic therapy: a CBP® case report.

Science.gov (United States)

Jaeger, Jason O; Oakley, Paul A; Moore, Robert R; Ruggeroli, Edward P; Harrison, Deed E

2018-01-01

[Purpose] To present the case of the resolution of right temporomandibular joint dysfunction (TMJD) following the correction of a right lateral head translation posture. [Subject and Methods] A 24 year old female reported facial pain and jaw clicking in the right TMJ. Radiography revealed a 19 mm right head (shift) translation posture. TMJ vibration analysis showed characteristic abnormalities for the right TMJ. The patient was treated with CBP ® technique mirror image ® left sided exercises, and traction methods as well as spinal manipulative therapy (SMT). [Results] After 36 treatments over a 12-week time period, a complete correction of the lateral head posture was achieved corresponding with a complete resolution of jaw pain and clicking. TMJ vibration analysis demonstrated normal right side TMJ characteristics following treatment. [Conclusion] Abnormal head/neck postures, such as lateral head translation, may be an unrealized source of TMJD and may be explained through the 'regional interdependence' model or by how seemingly unrelated anatomy may be associated with a primary complaint.

Quo Vadis medycyno regeneracyjna?: Quo Vadis Regenerative Medicine?

Science.gov (United States)

Ratajczak, Mariusz Z; Suszyńska, Malwina

2013-07-01

There are presented the most important sources of pluripotent stem cells for potential application in the regenerative medicine. This review summarizes also advantages and disadvantages for potential application of these cells in clinical medicine.

Machine Translation and Other Translation Technologies.

Science.gov (United States)

Melby, Alan

1996-01-01

Examines the application of linguistic theory to machine translation and translator tools, discusses the use of machine translation and translator tools in the real world of translation, and addresses the impact of translation technology on conceptions of language and other issues. Findings indicate that the human mind is flexible and linguistic…

[Ethical aspects of regenerative medicine, with special reference to embryonic stem cells and therapeutic cloning].

Science.gov (United States)

Imura, Hiroo

2003-03-01

Regenerative medicine is expected to be new therapeutic means for treating incurable diseases but requires serious bioethical consideration. Embryonic stem(ES) cells, that are pleuripotent cells suitable to regenerative medicine, can be used in Japan for investigative use under a strict control by guide-lines. On the other hand, use of embryo produced by nuclear transfer has not been allowed in Japan and further serious consideration is required. Some other ethical aspects of regenerative medicine are also discussed.

REGENERATIVE DESIGN PRACTICES IN NIGERIA: A CASE ...

African Journals Online (AJOL)

User

2017-07-01

Jul 1, 2017 ... a view to effectively implement the concept within the study area. ... REGENERATIVE DESIGN PRACTICES IN NIGERIA: A CASE STUDY OF NGOZIKA HOUSING .... could mean greater acceptance of new development by the public and .... human/environment relations based on the Cartesian separation of ...

Ultrastructural study of the chromatoid body in planarian regenerative cells

Energy Technology Data Exchange (ETDEWEB)

Hori, I. (Kanazawa Medical Univ., Ishikawa (Japan))

1982-04-01

The present paper deals with the ultrastructural changes of chromatoid bodies in planarian regenerative cells under normal and experimental conditions. A close relationship was usually observed between chromatoid bodies and pore regions of the nuclear envelope in these cells. The chromatoid bodies continued to decrease in size during cytodifferentiation of regenerative cells, though they did not disappear entirely throughout the regeneration processes. Cytochemistry and (/sup 3/H)uridine autoradiography have shown that the chromatoid body contains RNA. The typical morphological effect of actinomycin D became apparent in three organelles, i.e., nucleolus, polysome and chromatoid body. Ultrastructural changes in nucleoli were observed to occur after actinomycin treatment (20 ..mu..g/ml). The exposure to a higher dose of actinomycin (50 ..mu..g/ml) caused a decay of chromatoid bodies while nuclear envelopes retained numerous pores. Both the nucleoli and the chromatoid bodies disappeared in the sequential stages. Within the cytoplasm of such cells disintegration of a polysomal pattern was correlated with the disappearance of chromatoid bodies. The significance of the planarian chromatoid body is discussed in relation to differentiation of the regenerative cells.

Feasibility of Exploiting Celution^ System in Autologous Cell Therapy in Dokkyo Medical University Hospital:Safety and Reproducibility

OpenAIRE

Ken-ichi, Inoue; Hiroshi, Nomura; Ryoichi, Sohma; Kazumi, Akimoto; Naohiko, Kobayashi; Takao, Kamai; Tomonori, Yamanishi; Isao, Taguchi; Hiroki, Asato; Teruo, Inoue; Tomoyuki, Mitsumori; Hideki, Iwaguro; Ken-ichiro, Yoshida; Research Support Center, Dokkyo Medical University School Of Medicine:Center For Regenerative Medicine, Dokkyo Medical University School Of Medicine; Center For Regenerative Medicine, Dokkyo Medical University School Of Medicine:Department Of Plastic And Reconstructive Surgery, Dokkyo Medical University School Of Medicine

2014-01-01

In 2012, we established the Center for Regenerative Medicine in Dokkyo Medical University Hospital, and are now preparing the necessary equipment and preclinical evidence for cell therapy. Liposuction is a commonly used procedure in plastic surgery and the lipoaspirate is discarded as a medical waste. However, the lipoaspirate is known to contain abundant mesenchymal stem cells, and thus, it is currently one of the most feasible options of regenerative medicine. Several ongoing clinical trial...

Error-rate performance analysis of opportunistic regenerative relaying

KAUST Repository

Tourki, Kamel; Yang, Hongchuan; Alouini, Mohamed-Slim

2011-01-01

In this paper, we investigate an opportunistic relaying scheme where the selected relay assists the source-destination (direct) communication. In our study, we consider a regenerative opportunistic relaying scheme in which the direct path can

A Grading System To Evaluate Objectively the Strength of Pre-Clinical Data of Acute Neuroprotective Therapies for Clinical Translation in Spinal Cord Injury

Science.gov (United States)

Okon, Elena B.; Tsai, Eve; Beattie, Michael S.; Bresnahan, Jacqueline C.; Magnuson, David K.; Reier, Paul J.; McTigue, Dana M.; Popovich, Phillip G.; Blight, Andrew R.; Oudega, Martin; Guest, James D.; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

2011-01-01

Abstract The past three decades have seen an explosion of research interest in spinal cord injury (SCI) and the development of hundreds of potential therapies that have demonstrated some promise in pre-clinical experimental animal models. A growing number of these treatments are seeking to be translated into human clinical trials. Conducting such a clinical trial, however, is extremely costly, not only for the time and money required to execute it, but also for the limited resources that will then no longer be available to evaluate other promising therapies. The decision about what therapies have sufficient pre-clinical evidence of efficacy to justify testing in humans is therefore of utmost importance. Here, we have developed a scoring system for objectively grading the body of pre-clinical literature on neuroprotective treatments for acute SCI. The components of the system include an evaluation of a number of factors that are thought to be important in considering the “robustness” of a therapy's efficacy, including the animal species and injury models that have been used to test it, the time window of efficacy, the types of functional improvements effected by it, and whether efficacy has been independently replicated. The selection of these factors was based on the results of a questionnaire that was performed within the SCI research community. A modified Delphi consensus-building exercise was then conducted with experts in pre-clinical SCI research to refine the criteria and decide upon how to score them. Finally, the grading system was applied to a series of potential neuroprotective treatments for acute SCI. This represents a systematic approach to developing an objective method of evaluating the extent to which the pre-clinical literature supports the translation of a particular experimental treatment into human trials. PMID:20507235

Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.

Science.gov (United States)

Nafissi, Nafiseh; Foldvari, Marianna

2015-01-01

Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

NEUROPROTECTIVE THERAPIES IN GLAUCOMA: II. GENETIC NANOTECHNOLOGY TOOLS

Directory of Open Access Journals (Sweden)

Nafiseh eNafissi

2015-10-01

Full Text Available Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The field of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

Optimization of delivery strategies for cardiac cell therapy in ischemic heart disease

NARCIS (Netherlands)

van der Spoel, T.I.G.

2012-01-01

Cardiac cell therapy has been proposed as an alternative treatment option for patients after acute myocardial infarction (MI). Irrespective of the chosen regenerative strategy, it is essential to deliver sufficient number of cells to the infarcted myocardium to become effective which is important

Regenerative Potential of Ependymal Cells for Spinal Cord Injuries Over Time

Directory of Open Access Journals (Sweden)

Xiaofei Li

2016-11-01

Full Text Available Stem cells have a high therapeutic potential for the treatment of spinal cord injury (SCI. We have shown previously that endogenous stem cell potential is confined to ependymal cells in the adult spinal cord which could be targeted for non-invasive SCI therapy. However, ependymal cells are an understudied cell population. Taking advantage of transgenic lines, we characterize the appearance and potential of ependymal cells during development. We show that spinal cord stem cell potential in vitro is contained within these cells by birth. Moreover, juvenile cultures generate more neurospheres and more oligodendrocytes than adult ones. Interestingly, juvenile ependymal cells in vivo contribute to glial scar formation after severe but not mild SCI, due to a more effective sealing of the lesion by other glial cells. This study highlights the importance of the age-dependent potential of stem cells and post-SCI environment in order to utilize ependymal cell's regenerative potential.

Regenerative Payload for GSAT-3 & Advanced Communication ...

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Regenerative Payload for GSAT-3 & Advanced Communication Series Satellite. GSAT-4. 8 Ka -Band Spot Beams; 8 Narrow Band (64Kbps) Channels/ Beam; 1 Wide Band (2Mbps) Channel/ Beam;; 64 Kbps Signaling Channel; On-Board Switch Matrix; 8 Channel ...

Translational Control in Plasmodium and Toxoplasma Parasites

Science.gov (United States)

Joyce, Bradley R.; Sullivan, William J.; Nussenzweig, Victor

2013-01-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis. PMID:23243065

Translational control in Plasmodium and toxoplasma parasites.

Science.gov (United States)

Zhang, Min; Joyce, Bradley R; Sullivan, William J; Nussenzweig, Victor

2013-02-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.

New frontier in regenerative medicine: site-specific gene correction in patient-specific induced pluripotent stem cells.

Science.gov (United States)

Garate, Zita; Davis, Brian R; Quintana-Bustamante, Oscar; Segovia, Jose C

2013-06-01

Advances in cell and gene therapy are opening up new avenues for regenerative medicine. Because of their acquired pluripotency, human induced pluripotent stem cells (hiPSCs) are a promising source of autologous cells for regenerative medicine. They show unlimited self-renewal while retaining the ability, in principle, to differentiate into any cell type of the human body. Since Yamanaka and colleagues first reported the generation of hiPSCs in 2007, significant efforts have been made to understand the reprogramming process and to generate hiPSCs with potential for clinical use. On the other hand, the development of gene-editing platforms to increase homologous recombination efficiency, namely DNA nucleases (zinc finger nucleases, TAL effector nucleases, and meganucleases), is making the application of locus-specific gene therapy in human cells an achievable goal. The generation of patient-specific hiPSC, together with gene correction by homologous recombination, will potentially allow for their clinical application in the near future. In fact, reports have shown targeted gene correction through DNA-Nucleases in patient-specific hiPSCs. Various technologies have been described to reprogram patient cells and to correct these patient hiPSCs. However, no approach has been clearly more efficient and safer than the others. In addition, there are still significant challenges for the clinical application of these technologies, such as inefficient differentiation protocols, genetic instability resulting from the reprogramming process and hiPSC culture itself, the efficacy and specificity of the engineered DNA nucleases, and the overall homologous recombination efficiency. To summarize advances in the generation of gene corrected patient-specific hiPSCs, this review focuses on the available technological platforms, including their strengths and limitations regarding future therapeutic use of gene-corrected hiPSCs.

Regenerative adsorbent heat pump

Science.gov (United States)

Jones, Jack A. (Inventor)

1991-01-01

A regenerative adsorbent heat pump process and system is provided which can regenerate a high percentage of the sensible heat of the system and at least a portion of the heat of adsorption. A series of at least four compressors containing an adsorbent is provided. A large amount of heat is transferred from compressor to compressor so that heat is regenerated. The process and system are useful for air conditioning rooms, providing room heat in the winter or for hot water heating throughout the year, and, in general, for pumping heat from a lower temperature to a higher temperature.

Highly Efficient, Durable Regenerative Solid Oxide Stack, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Precision Combustion, Inc. (PCI) proposes to develop a highly efficient regenerative solid oxide stack design. Novel structural elements allow direct internal...

Performance enhancement of a solar still using cotton regenerative medium

Directory of Open Access Journals (Sweden)

Thirumalai Gopal Sakthivel

2017-01-01

Full Text Available This paper presents the performance of a single slope solar still using cotton cloth regenerative medium. The performance was evaluated under the metrological conditions of Chennai city in India during the summer months of 2016. Two single-slope solar stills are fabricated with an effective area of 0.5 m2 with various thicknesses (2, 4, 6, and 8 mm of cotton cloth were used for the performance comparison. The results showed, the solar still with 6 mm thick cotton assisted regenerative solar still has about 28% improved productivity when compared to conventional solar still.

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

Science.gov (United States)

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. © FASEB.

Mechanism analysis and evaluation methodology of regenerative braking contribution to energy efficiency improvement of electrified vehicles

International Nuclear Information System (INIS)

Lv, Chen; Zhang, Junzhi; Li, Yutong; Yuan, Ye

2015-01-01

Highlights: • The energy flow of an electric vehicle with regenerative brake is analyzed. • Methodology for measuring the regen brake contribution is discussed. • Evaluation parameters of regen brake contribution are proposed. • Vehicle tests are carried out on chassis dynamometer. • Test results verify the evaluation method and parameters proposed. - Abstract: This article discusses the mechanism and evaluation methods of contribution brought by regenerative braking to electric vehicle’s energy efficiency improvement. The energy flow of an electric vehicle considering the braking energy regeneration was analyzed. Then, methodologies for measuring the contribution made by regenerative brake to vehicle energy efficiency improvement were introduced. Based on the energy flow analyzed, two different evaluation parameters were proposed. Vehicle tests were carried out on chassis dynamometer under typical driving cycles with three different control strategies. The experimental results the difference between the proposed two evaluation parameters, and demonstrated the feasibility and effectiveness of the evaluation methodologies proposed

Active Magnetic Regenerative Liquefier

Energy Technology Data Exchange (ETDEWEB)

Barclay, John A. [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Oseen-Send, Kathryn [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ferguson, Luke [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Pouresfandiary, Jamshid [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Cousins, Anand [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ralph, Heather [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Hampto, Tom [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States)

2016-01-12

This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

Development of a computer code for a regenerative Rankine cycle analysis

International Nuclear Information System (INIS)

Wi, Myung Hwan; Kim, Seong O; Choi, Seok Ki; Kim, Jin Hwan

2005-01-01

A regenerative Rankine cycle can increase the thermal efficiency of a steam system without increasing the steam pressure and temperature. The regenerative process involves heating the feedwater on its return trip to the steam generator by extracting steam at various stages of the turbine and transferring the energy to the feedwater via a feedwater heater. Some real plants use more than five feedwater heaters to enhance the cycle efficiency. However, the optimum number of feedwater heaters required is determined by balancing the efficiency improvement against the capital investment for a given cycle. In the present study, the computer code, TAOPCS, for the thermodynamic analysis of a regenerative steam cycle was developed to optimally design and accurately analyze the behavior of the power conversion system of Korea Advance Liquid Metal Reactor (KALIMER). In order to understand the functions and the characteristics of the code, the main features of the TAPCS were described and the example results are presented in this paper

Nonclinical safety strategies for stem cell therapies

Energy Technology Data Exchange (ETDEWEB)

Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

2012-08-01

Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

Nonclinical safety strategies for stem cell therapies

International Nuclear Information System (INIS)

Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

2012-01-01

Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

Use of elastomers in regenerative braking systems

Science.gov (United States)

The storage of potential energy as strain energy in elastomers was investigated. The evolution of the preferred stressing scheme is described, and test results on full-size elastomeric energy storage units sized for an automotive regenerative braking system application are presented. The need for elastomeric material improvements is also discussed.

New model of inverting substation for DC traction with regenerative braking system

Science.gov (United States)

Omar, Abdul Malek Saidina; Samat, Ahmad Asri Abd; Isa, Siti Sarah Mat; Shamsuddin, Sarah Addyani; Jamaludin, Nur Fadhilah; Khyasudeen, Muhammad Farris

2017-08-01

This paper presents a power electronic devices application focus on modeling, analysis, and control of switching power converter in the inverting DC substation with regenerative braking system which is used to recycle the surplus regenerative power by feed it back to the main AC grid. The main objective of this research is to improve the switching power electronic converter of the railway inverting substation and optimize the maximum kinetic energy recovery together with minimum power losses from the railway braking system. Assess performance including efficiency and robustness will be evaluated in order to get the best solution for the design configuration. Research methodology included mathematical calculation, simulation, and detail analysis on modeling of switching power converter on inverting substation. The design stage separates to four main areas include rectification mode, regenerative mode, control inverter mode and filtering mode. The simulation result has shown that the regenerative inverter has a capability to accept a maximum recovery power on the regeneration mode. Total energy recovery has increase and power losses have decreases because inverter abilities to transfer the surplus energy back to the main AC supply. An Inverter controller with PWM Generator and PI Voltage Regulator has been designed to control voltage magnitude and frequency of the DC traction system.

Progenitor cells for regenerative medicine and consequences of ART and cloning-associated epimutations.

Science.gov (United States)

Laprise, Shari L

2010-06-01

The "holy grail" of regenerative medicine is the identification of an undifferentiated progenitor cell that is pluripotent, patient specific, and ethically unambiguous. Such a progenitor cell must also be able to differentiate into functional, transplantable tissue, while avoiding the risks of immune rejection. With reports detailing aberrant genomic imprinting associated with assisted reproductive technologies (ART) and reproductive cloning, the idea that human embryonic stem cells (hESCs) derived from surplus in vitro fertilized embryos or nuclear transfer ESCs (ntESCs) harvested from cloned embryos may harbor dangerous epigenetic errors has gained attention. Various progenitor cell sources have been proposed for human therapy, from hESCs to ntESCs, and from adult stem cells to induced pluripotent stem cells (iPS and piPS cells). This review highlights the advantages and disadvantages of each of these technologies, with particular emphasis on epigenetic stability.

Clinical application of cell, gene and tissue therapies in Spain.

Science.gov (United States)

Gálvez-Martín, P; Ruiz, A; Clares, B

2018-05-01

Scientific and technical advances in the areas of biomedicine and regenerative medicine have enabled the development of new treatments known as "advanced therapies", which encompass cell therapy, genetics and tissue engineering. The biologic products that can be manufactured from these elements are classified from the standpoint of the Spanish Agency of Medication and Health Products in advanced drug therapies, blood products and transplants. This review seeks to provide scientific and administrative information for clinicians on the use of these biologic resources. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Parameters Design for a Parallel Hybrid Electric Bus Using Regenerative Brake Model

Directory of Open Access Journals (Sweden)

Zilin Ma

2014-01-01

Full Text Available A design methodology which uses the regenerative brake model is introduced to determine the major system parameters of a parallel electric hybrid bus drive train. Hybrid system parameters mainly include the power rating of internal combustion engine (ICE, gear ratios of transmission, power rating, and maximal torque of motor, power, and capacity of battery. The regenerative model is built in the vehicle model to estimate the regenerative energy in the real road conditions. The design target is to ensure that the vehicle meets the specified vehicle performance, such as speed and acceleration, and at the same time, operates the ICE within an expected speed range. Several pairs of parameters are selected from the result analysis, and the fuel saving result in the road test shows that a 25% reduction is achieved in fuel consumption.

Hypoxia-based strategies for regenerative dentistry-Views from the different dental fields.

Science.gov (United States)

Müller, Anna Sonja; Janjić, Klara; Lilaj, Bledar; Edelmayer, Michael; Agis, Hermann

2017-09-01

The understanding of the cell biological processes underlying development and regeneration of oral tissues leads to novel regenerative approaches. Over the past years, knowledge on key roles of the hypoxia-based response has become more profound. Based on these findings, novel regenerative approaches for dentistry are emerging, which target cellular oxygen sensors. These approaches include hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in studies on hypoxia and hypoxia-based strategies in regenerative dentistry highlights the growing attention to hypoxia's role in regeneration and its underlying biology, as well as its application in a therapeutic setting. In this narrative review, we present the current knowledge on the role of hypoxia in oral tissues and review the proposed hypoxia-based approaches in different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Looking into the Future: Toward Advanced 3D Biomaterials for Stem-Cell-Based Regenerative Medicine.

Science.gov (United States)

Liu, Zhongmin; Tang, Mingliang; Zhao, Jinping; Chai, Renjie; Kang, Jiuhong

2018-04-01

Stem-cell-based therapies have the potential to provide novel solutions for the treatment of a variety of diseases, but the main obstacles to such therapies lie in the uncontrolled differentiation and functional engraftment of implanted tissues. The physicochemical microenvironment controls the self-renewal and differentiation of stem cells, and the key step in mimicking the stem cell microenvironment is to construct a more physiologically relevant 3D culture system. Material-based 3D assemblies of stem cells facilitate the cellular interactions that promote morphogenesis and tissue organization in a similar manner to that which occurs during embryogenesis. Both natural and artificial materials can be used to create 3D scaffolds, and synthetic organic and inorganic porous materials are the two main kinds of artificial materials. Nanotechnology provides new opportunities to design novel advanced materials with special physicochemical properties for 3D stem cell culture and transplantation. Herein, the advances and advantages of 3D scaffold materials, especially with respect to stem-cell-based therapies, are first outlined. Second, the stem cell biology in 3D scaffold materials is reviewed. Third, the progress and basic principles of developing 3D scaffold materials for clinical applications in tissue engineering and regenerative medicine are reviewed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Translating Stem Cell Research to Cardiac Disease Therapies: Pitfalls and Prospects for Improvement

Science.gov (United States)

Rosen, Michael R.; Myerburg, Robert J.; Francis, Darrel P.; Cole, Graham D.; Marbán, Eduardo

2014-01-01

Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of articles focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies. The first section by Rosen and Myerburg is an independent review that analyzes the basic science and translational strategies supporting the rapid advance of stem cell technology to the clinic, the philosophies behind them, trial designs, and means for going forward that may impact favorably on progress. The second and third sections were collected in response to the initial section of this review. The commentary by Francis and Cole discusses the Rosen and Myerburg review and details how trial outcomes can be affected by noise, poor trial design (particularly the absence of blinding), and normal human tendencies toward optimism and denial. The final, independent article by Marbán takes a different perspective concerning the potential for positive impact of stem cell research applied to heart disease and future prospects for its clinical application. PMID:25169179

Mesenchymal dental stem cells in regenerative dentistry.

Science.gov (United States)

Rodríguez-Lozano, Francisco-Javier; Insausti, Carmen-Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María-del-Carmen; Meseguer, Luis; Meseguer-Henarejos, Ana-Belén; Marín, Noemí; Martínez, Salvador; Moraleda, José-María

2012-11-01

In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

Science.gov (United States)

Portas, M; Mansilla, E; Drago, H; Dubner, D; Radl, A; Coppola, A; Di Giorgio, M

2016-09-01

Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy. © World Health Organisation 2016. All rights reserved. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.

The Continuing Challenges of Translational Research: Clinician-Scientists’ Perspective

Directory of Open Access Journals (Sweden)

Shervanthi Homer-Vanniasinkam

2012-01-01

Full Text Available Over the last twenty years, revolutionary advances in biomedicine including gene therapy, stem cell research, proteomics, genomics and nanotechnology have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. Over the past ten years, funding bodies in the USA and UK such as the National Institutes of Health (NIH and the Medical Research Council (MRC have been driving translational research by defining and tackling the hurdles but more still remains to be achieved. This article discusses the ongoing challenges translational researchers face and outlines recent initiatives to tackle these including the new changes to translational funding schemes proposed by the NIH and the MRC and the launch of the “European Advanced Translational Research InfraStructure in Medicine” (EATRIS. It is anticipated that initiatives such as these will not only strengthen translational biomedical research programmes already initiated but should lead to rapid benefits to patients and society.

Development of Regenerative Braking Co-operative Control System for Automatic Transmission-based Hybrid Electric Vehicle using Electronic Wedge Brake

OpenAIRE

Ko, Jiweon; Ko, Sungyeon; Bak, Yongsun; Jang, Mijeong; Yoo, Byoungsoo; Cheon, Jaeseung; Kim, Hyunsoo

2013-01-01

This research proposes a regenerative braking co-operative control system for the automatic transmission (AT)-based hybrid electric vehicle (HEV). The brake system of the subject HEV consists of the regenerative braking and the electronic wedge brake (EWB) friction braking for the front wheel, and the hydraulic friction braking for the rear wheel. A regenerative braking co-operative control algorithm is suggested for the regenerative braking and friction braking, which distributes the braking...

Prospect of stem cell conditioned medium in regenerative medicine.

Science.gov (United States)

Pawitan, Jeanne Adiwinata

2014-01-01

Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerative medicine. To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight into their prospect of application in various diseases. Systematic review using keywords "stem cell" and "conditioned medium" or "secretome" and "therapy." Data concerning treated conditions/diseases, type of cell that was cultured, medium and supplements to culture the cells, culture condition, CM processing, growth factors and other secretions that were analyzed, method of application, and outcome were noted, grouped, tabulated, and analyzed. Most of CM using studies showed good results. However, the various CM, even when they were derived from the same kind of cells, were produced by different condition, that is, from different passage, culture medium, and culture condition. The growth factor yields of the various types of cells were available in some studies, and the cell number that was needed to produce CM for one application could be computed. Various stem cell-derived conditioned media were tested on various diseases and mostly showed good results. However, standardized methods of production and validations of their use need to be conducted.

Advanced Space Power Systems (ASPS): Regenerative Fuel Cells (RFC)

Data.gov (United States)

National Aeronautics and Space Administration — The objective of the regenerative fuel cell project element is to develop power and energy storage technologies that enable new capabilities for future human space...

A Study on Control Strategy of Regenerative Braking in the Hydraulic Hybrid Vehicle Based on ECE Regulations

Directory of Open Access Journals (Sweden)

Tao Liu

2013-01-01

Full Text Available This paper establishes a mathematic model of composite braking in the hydraulic hybrid vehicle and analyzes the constraint condition of parallel regenerative braking control algorithm. Based on regenerative braking system character and ECE (Economic Commission of Europe regulations, it introduces the control strategy of regenerative braking in parallel hydraulic hybrid vehicle (PHHV. Finally, the paper establishes the backward simulation model of the hydraulic hybrid vehicle in Matlab/simulink and makes a simulation analysis of the control strategy of regenerative braking. The results show that this strategy can equip the hydraulic hybrid vehicle with strong brake energy recovery power in typical urban drive state.

Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering.

Science.gov (United States)

Obregon, F; Vaquette, C; Ivanovski, S; Hutmacher, D W; Bertassoni, L E

2015-09-01

Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side. © International & American Associations for Dental Research 2015.

Induced Pluripotent Stem Cells from Nonhuman Primates.

Science.gov (United States)

Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

2016-01-01

Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

A regenerative biology view on artificial tissue construction and 3D bioprinting: what may we learn from natural regenerative phenomena?

DEFF Research Database (Denmark)

Lauridsen, Henrik

2017-01-01

The implications of the low tissue regenerative potential in humans are severe and widespread. Several of our major diseases are direct results of this deficiency that leaves us vulnerable to events of tissue damage. This is opposed to some animal groups, such as the urodele amphibians (salamanders...

Educational tool for modeling and simulation of a closed regenerative life support system

Science.gov (United States)

Arai, Tatsuya; Fanchiang, Christine; Aoki, Hirofumi; Newman, Dava J.

For long term missions on the moon and Mars, regenerative life support systems emerge as a promising key technology for sustaining successful explorations with reduced re-supply logistics and cost. The purpose of this study was to create a simple model of a regenerative life support system which allows preliminary investigation of system responses. A simplified regenerative life support system was made with MATLAB Simulink ™. Mass flows in the system were simplified to carbon, water, oxygen and carbon dioxide. The subsystems included crew members, animals, a plant module, and a waste processor, which exchanged mass into and out of mass reservoirs. Preliminary numerical simulations were carried out to observe system responses. The simplified life support system model allowed preliminary investigation of the system response to perturbations such as increased or decreased number of crew members. The model is simple and flexible enough to add new components, and also possible to numerically predict non-linear subsystem functions and responses. Future work includes practical issues such as energy efficiency, air leakage, nutrition, and plant growth modeling. The model functions as an effective teaching tool about how a regenerative advanced life support system works.

Energy recapture through deceleration - regenerative braking in electric vehicles from a user perspective.

Science.gov (United States)

Cocron, Peter; Bühler, Franziska; Franke, Thomas; Neumann, Isabel; Dielmann, Benno; Krems, Josef F

2013-01-01

We report results from a 1-year field study (N = 80) on user interactions with regenerative braking in electric vehicles. Designed to recapture energy in vehicles with electric powertrains, regenerative braking has an important influence on both the task of driving and energy consumption. Results from user assessments and data from onboard data loggers indicate that most drivers quickly learned to interact with the system, which was triggered via accelerator. Further, conventional braking manoeuvres decreased significantly as the majority of deceleration episodes could only be executed through regenerative braking. Still, some drivers reported difficulties when adapting to the system. These difficulties could be addressed by offering different levels of regeneration so that the intensity of the deceleration could be individually modified. In general, the system is trusted and regarded as a valuable tool for prolonging range. Regenerative braking in electric vehicles has direct implications for the driving task. We found that drivers quickly learn to use and accept a system, which is triggered via accelerator. For those reporting difficulties in the interaction, it appears reasonable to integrate options to customise or switch off the system.

Concise Review: Pluripotent Stem Cell-Derived Cardiac Cells, A Promising Cell Source for Therapy of Heart Failure: Where Do We Stand?

Science.gov (United States)

Gouadon, Elodie; Moore-Morris, Thomas; Smit, Nicoline W; Chatenoud, Lucienne; Coronel, Ruben; Harding, Sian E; Jourdon, Philippe; Lambert, Virginie; Rucker-Martin, Catherine; Pucéat, Michel

2016-01-01

Heart failure is still a major cause of hospitalization and mortality in developed countries. Many clinical trials have tested the use of multipotent stem cells as a cardiac regenerative medicine. The benefit for the patients of this therapeutic intervention has remained limited. Herein, we review the pluripotent stem cells as a cell source for cardiac regeneration. We more specifically address the various challenges of this cell therapy approach. We question the cell delivery systems, the immune tolerance of allogenic cells, the potential proarrhythmic effects, various drug mediated interventions to facilitate cell grafting and, finally, we describe the pathological conditions that may benefit from such an innovative approach. As members of a transatlantic consortium of excellence of basic science researchers and clinicians, we propose some guidelines to be applied to cell types and modes of delivery in order to translate pluripotent stem cell cardiac derivatives into safe and effective clinical trials. © 2015 AlphaMed Press.

Electrolyzer for NASA Lunar Regenerative Fuel Cells, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Water electrolyzer stacks are a key component of regenerative fuel cells, designed to replace batteries as a means of storing electric energy on the lunar surface....

Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation......Due to the growing uptake of translation technology in the language industry and its documented impact on the translation profession, translation students and scholars need in-depth and empirically founded knowledge of the nature and influences of translation technology (e.g. Christensen....../Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...

Regenerative adsorption distillation system

KAUST Repository

Ng, Kim Choon; Thu, Kyaw; Amy, Gary; Chunggaze, Mohammed; Al-Ghasham, Tawfiq

2013-01-01

There is provided a regenerative adsorption distillation system comprising a train of distillation effects in fluid communication with each other. The train of distillation effects comprises at least one intermediate effect between the first and last distillation effects of the train, each effect comprising a vessel and a condensing tube for flow of a fluid therein. The system further comprises a pair of adsorption-desorption beds in vapour communication with the last effect and at least one intermediate effect, wherein the beds contain an adsorbent that adsorbs vapour from the last effect and transmits desorbed vapour into at least one of the intermediate effect.

Regenerative adsorption distillation system

KAUST Repository

Ng, Kim Choon

2013-12-26

There is provided a regenerative adsorption distillation system comprising a train of distillation effects in fluid communication with each other. The train of distillation effects comprises at least one intermediate effect between the first and last distillation effects of the train, each effect comprising a vessel and a condensing tube for flow of a fluid therein. The system further comprises a pair of adsorption-desorption beds in vapour communication with the last effect and at least one intermediate effect, wherein the beds contain an adsorbent that adsorbs vapour from the last effect and transmits desorbed vapour into at least one of the intermediate effect.

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.

Science.gov (United States)

Fraser, John K; Hicok, Kevin C; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution ® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

REAC regenerative treatment efficacy in experimental chondral lesions: a pilot study on ovine animal model

Directory of Open Access Journals (Sweden)

Sanna Passino E

2017-09-01

Full Text Available Eraldo Sanna Passino,1,2 Stefano Rocca,1 Sabrina Caggiu,1 Nicolò Columbano,1,2 Alessandro Castagna,3 Vania Fontani,3–5 Salvatore Rinaldi3–51Department of Veterinary Medicine, University of Sassari, Sassari, Italy; 2Comparative Surgery Research Laboratory, University of Sassari, Sassari, Italy; 3Department of Regenerative Medicine, Rinaldi Fontani Institute, Florence, Italy; 4Research Department, Rinaldi Fontani Foundation, Florence, Italy; 5Research Department, IRF Shanghai Biomedical Sciences, Shanghai, People’s Republic of China Abstract: Radioelectric asymmetric conveyor (REAC technology is a platform designed to optimize cell polarity. Cell polarity is a universal biological phenomenon that is implicated in cell differentiation, proliferation, morphogenesis, aging, and rejuvenation. In this work, we investigate a timing and administration protocol for tissue optimization regenerative treatment type C, in order to treat aging-related chondral damage or injuries and gain insights into regenerative processes of articular cartilage in humans. The chondral lesion produced in this study in an animal model (6 knee joints of 4 adult sheep was 6 mm in diameter and about 2 mm deep. These lesions, which did not involve subchondral bone, tend to increase in size and depth and are not completely repaired with normal hyaline articular cartilage since adult articular cartilage is avascular and has a very slow turnover at the cellular and molecular level. Moreover, the hydration of articular cartilage is reduced with aging and with decreased mitotic activity, synthesis, and population size of chondrocytes. Six months posttreatment, lesions appeared filled, though not completely, with newly generated tissue of the light opalescent color of healthy articular cartilage, which otherwise covered the underlying subchondral bone. The newly formed tissue surface appeared to be quite regular. Nearly complete regeneration of subchondral bone occurred, with

PRMT7 Preserves Satellite Cell Regenerative Capacity

Directory of Open Access Journals (Sweden)

Roméo Sébastien Blanc

2016-02-01

Full Text Available Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells, which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.

Multiple excitation regenerative amplifier inertial confinement system

International Nuclear Information System (INIS)

George, V.E.; Haas, R.A.; Krupke, W.F.; Schlitt, L.G.

1980-01-01

The invention relates to apparatus and methods for producing high intensity laser radiation generation which is achieved through an optical amplifier-storage ring design. One or two synchronized, counterpropagating laser pulses are injected into a regenerative amplifier cavity and amplified by gain media which are pumped repetitively by electrical or optical means. The gain media excitation pulses are tailored to efficiently amplify the laser pulses during each transit. After the laser pulses have been amplified to the desired intensity level, they are either switched out of the cavity by some switch means, as for example an electro-optical device, for any well known laser end uses, or a target means may be injected into the regenerative amplifier cavity in such a way as to intercept simultaneously the counterpropagating laser pulses. One such well known end uses to which this invention is intended is for production of high density and temperature plasmas suitable for generating neutrons, ions and x-rays and for studying matter heated by high intensity laser radiation

Enhanced Regenerative Braking Strategies for Electric Vehicles: Dynamic Performance and Potential Analysis

OpenAIRE

Boyi Xiao; Huazhong Lu; Hailin Wang; Jiageng Ruan; Nong Zhang

2017-01-01

A regenerative braking system and hydraulic braking system are used in conjunction in the majority of electric vehicles worldwide. We propose a new regenerative braking distribution strategy that is based on multi-input fuzzy control logic while considering the influences of the battery’s state of charge, the brake strength and the motor speed. To verify the braking performance and recovery economy, this strategy was applied to a battery electric vehicle model and compared with two other impr...

Complementary and integrative therapies for lower urinary tract diseases.

Science.gov (United States)

Raditic, Donna M

2015-07-01

Consumer use of integrative health care is growing, but evidence-based research on its efficacy is limited. Research of veterinary lower urinary tract diseases could be translated to human medicine because veterinary patients are valuable translational models for human urinary tract infection and urolithiasis. An overview of complementary therapies for lower urinary tract disease includes cranberry supplements, mannose, oral probiotics, acupuncture, methionine, herbs, or herbal preparations. Therapies evaluated in dogs and cats, in vitro canine cells, and other relevant species, in vivo and in vitro, are presented for their potential use as integrative therapies for veterinary patients and/or translational research. Copyright © 2015 Elsevier Inc. All rights reserved.

A Study on Control Strategy of Regenerative Braking in the Hydraulic Hybrid Vehicle Based on ECE Regulations

OpenAIRE

Liu, Tao; Zheng, Jincheng; Su, Yongmao; Zhao, Jinghui

2013-01-01

This paper establishes a mathematic model of composite braking in the hydraulic hybrid vehicle and analyzes the constraint condition of parallel regenerative braking control algorithm. Based on regenerative braking system character and ECE (Economic Commission of Europe) regulations, it introduces the control strategy of regenerative braking in parallel hydraulic hybrid vehicle (PHHV). Finally, the paper establishes the backward simulation model of the hydraulic hybrid vehicle in Matlab/simul...

An ultrastructural study of the chromatoid body in planarian regenerative cells

International Nuclear Information System (INIS)

Hori, Isao

1982-01-01

The present paper deals with the ultrastructural changes of chromatoid bodies in planarian regenerative cells under normal and experimental conditions. A close relationship was usually observed between chromatoid bodies and pore regions of the nuclear envelope in these cells. The chromatoid bodies continued to decrease in size during cytodifferentiation of regenerative cells, though they did not disappear entirely throughout the regeneration processes. Cytochemistry and [ 3 H]uridine autoradiography have shown that the chromatoid body contains RNA. The typical morphological effect of actinomycin D became apparent in three organelles, i.e., nucleolus, polysome and chromatoid body. Ultrastructural changes in nucleoli were observed to occur after actinomycin treatment (20 μg/ml). The exposure to a higher dose of actinomycin (50 μg/ml) caused a decay of chromatoid bodies while nuclear envelopes retained numerous pores. Both the nucleoli and the chromatoid bodies disappeared in the sequential stages. Within the cytoplasm of such cells disintegration of a polysomal pattern was correlated with the disappearance of chromatoid bodies. The significance of the planarian chromatoid body is discussed in relation to differentiation of the regenerative cells. (author)

Downward Slope Driving Control for Electric Powered Wheelchair Based on Capacitor Regenerative Brake

Science.gov (United States)

Seki, Hirokazu; Takahashi, Yoshiaki

This paper describes a novel capacitor regenerative braking control scheme of electric powered wheelchairs for efficient driving on downward slopes. An electric powered wheelchair, which generates the driving force by electric motors, is expected to be widely used as a mobility support system for elderly people and disabled people; however the energy efficiency has to be further improved because it is driven only by battery energy. This study proposes a capacitor regenerative braking circuit and two types of velocity control schemes with variable duty ratio. The proposed regenerative braking circuit is based on the step-up/down circuit with additional resistance and connects right and left motors in series in order to obtain a larger braking power. Some driving experiments on a practical downward slope show the effectiveness of the proposed control system.

A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

Energy Technology Data Exchange (ETDEWEB)

Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Tautenhahn, Hans-Michael, E-mail: hans-michael.tautenhahn@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany); Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [University Hospital Ulm, First Department of Medicine, Albert-Einstein-Allee 23, Ulm D-89081 (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany)

2014-02-15

Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

International Nuclear Information System (INIS)

Brückner, Sandra; Tautenhahn, Hans-Michael; Winkler, Sandra; Stock, Peggy; Dollinger, Matthias; Christ, Bruno

2014-01-01

Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

Singlet-oxygen therapy. Scientific and methodological materials

OpenAIRE

Chukhraiev, N.; Chukhraieva, E.; Gun'ko, M.; Kurik, L.; Lomeiko, S.; Marushko, Y.; Samosyuk, N.; Tkalina, A.; Vladimirov, A.; Unichenko, A.; Zavorotnaya, R.; Zukow, W.

2018-01-01

Radomska Szkoła Wyższa w Radomiu MEDICAL INNOVATIVE TECHNOLOGIES SINGLET-OXYGEN THERAPY Scientific and methodological materials 2018 This edition had extended and translated from ukrainian Edited by Chukhraiev N., Vladimirov A., Zukow W. Radom, Kyiv Radomska Szkoła Wyższa w Radomiu MEDICAL INNOVATIVE TECHNOLOGIES SINGLET-OXYGEN THERAPY Scientific and methodological materials 2018 This edition had extended and translated from ukrainian Edited by ...

Novel Therapy for Bone Regeneration in Large Segmental Defects

Science.gov (United States)

2017-12-01

Nanohydrox- yapatite- coated electrospun poly(L-lactide) nanofibers enhance osteogenic differentiation of stem cells and induce ectopic bone formation... Bone Regeneration in a Large Animal Critical Sized Defect Model, Second Annual Symposium on Cell Therapy and Regenerative Medicine, 2016 4...osteogenic cells and growth factors demonstrated success in facilitating bone regeneration in these cases. However, due to the lack of mechanical property

New results on performance analysis of opportunistic regenerative relaying

KAUST Repository

Tourki, Kamel; Yang, Hongchuan; Alouini, Mohamed-Slim; Qaraqe, Khalid A.

2013-01-01

In this paper, we investigate an opportunistic relaying scheme where the selected relay assists the source-destination (direct) communication. In our study, we consider a regenerative opportunistic relaying scheme in which the direct path may

Adaptive Regenerative Braking in Electric Vehicles

OpenAIRE

Kubaisi, Rayad

2018-01-01

Elektrofahrzeuge fahren lokal emissionsfrei und tragen damit dazu bei, die Emissionen in Städten zu reduzieren. Zusätzlich, zeichnen sich Elektrofahrzeuge durch ein dynamisches Fahrverhalten aus. Nachteilig wirkt sich bei den meisten Elektrofahrzeugen, die geringe Reichweite auf die Akzeptanz bei Neuwagenkäufern aus. Eine der Maßnahmen zur Erhöhung der Reichweite von Elektrofahrzeuge ist das regenerative Bremsen. Hierbei wird die kinetische Energie des Fahrzeugs durch generatorisches...

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

Science.gov (United States)

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Image-aided Suicide Gene Therapy Utilizing Multifunctional hTERT-targeting Adenovirus for Clinical Translation in Hepatocellular Carcinoma.

Science.gov (United States)

Kim, Yun-Hee; Kim, Kyung Tae; Lee, Sang-Jin; Hong, Seung-Hee; Moon, Ju Young; Yoon, Eun Kyung; Kim, Sukyoung; Kim, Eun Ok; Kang, Se Hun; Kim, Seok Ki; Choi, Sun Il; Goh, Sung Ho; Kim, Daehong; Lee, Seong-Wook; Ju, Mi Ha; Jeong, Jin Sook; Kim, In-Hoo

2016-01-01

Trans-splicing ribozyme enables to sense and reprogram target RNA into therapeutic transgene and thereby becomes a good sensing device for detection of cancer cells, judging from transgene expression. Previously we proposed PEPCK-Rz-HSVtk (PRT), hTERT targeting trans-splicing ribozyme (Rz) driven by liver-specific promoter phosphoenolpyruvate carboxykinase (PEPCK) with downstream suicide gene, herpes simplex virus thymidine kinase (HSVtk) for hepatocellular carcinoma (HCC) gene therapy. Here, we describe success of a re-engineered adenoviral vector harboring PRT in obtaining greater antitumor activity with less off-target effect for clinical application as a theranostics. We introduced liver-selective apolipoprotein E (ApoE) enhancer to the distal region of PRT unit to augment activity and liver selectivity of PEPCK promoter, and achieved better transduction into liver cancer cells by replacement of serotype 35 fiber knob on additional E4orf1-4 deletion of E1&E3-deleted serotype 5 back bone. We demonstrated that our refined adenovirus harboring PEPCK/ApoE-Rz-HSVtk (Ad-PRT-E) achieved great anti-tumor efficacy and improved ability to specifically target HCC without damaging normal hepatocytes. We also showed noninvasive imaging modalities were successfully employed to monitor both how well a therapeutic gene (HSVtk) was expressed inside tumor and how effectively a gene therapy took an action in terms of tumor growth. Collectively, this study suggests that the advanced therapeutic adenoviruses Ad-PRT-E and its image-aided evaluation system may lead to the powerful strategy for successful clinical translation and the development of clinical protocols for HCC therapy.

MicroRNAs in Tissue Engineering and Regenerative Medicine

NARCIS (Netherlands)

Krenning, Guido; Harmsen, Martin; Sen, Chandan

2015-01-01

The body has a large regenerative capacity to cope with the continuous adverse challenges of high-calorie diets, aging, inflammation, and wear and tear, as well as acute injuries such as myocardial infarction. However, if the amount of sustained damage exceeds the body’s repair capacity,

Translating gene transfer: a stalled effort.

Science.gov (United States)

Greenberg, Alexandra J; McCormick, Jennifer; Tapia, Carmen J; Windebank, Anthony J

2011-08-01

The journey of gene transfer from laboratory to clinic has been slow and fraught with many challenges and barriers. Despite the development of the initial technology in the early 1970s, a standard clinical treatment involving "gene therapy" remains to be seen. Furthermore, much was written about the technology in the early 1990s, but since then, not much has been written about the journey of gene transfer. The translational path of gene transfer thus far, both pitfalls and successes, can serve as a study not only in navigating ethical and safety concerns, but also in the importance of scientist-public interactions. Here, we examine the translational progress of gene transfer and what can be gleaned from its history. © 2011 Wiley Periodicals, Inc.

Cooperative Control of Regenerative Braking and Antilock Braking for a Hybrid Electric Vehicle

Directory of Open Access Journals (Sweden)

Guodong Yin

2013-01-01

Full Text Available A new cooperative braking control strategy (CBCS is proposed for a parallel hybrid electric vehicle (HEV with both a regenerative braking system and an antilock braking system (ABS to achieve improved braking performance and energy regeneration. The braking system of the vehicle is based on a new method of HEV braking torque distribution that makes the antilock braking system work together with the regenerative braking system harmoniously. In the cooperative braking control strategy, a sliding mode controller (SMC for ABS is designed to maintain the wheel slip within an optimal range by adjusting the hydraulic braking torque continuously; to reduce the chattering in SMC, a boundary-layer method with moderate tuning of a saturation function is also investigated; based on the wheel slip ratio, battery state of charge (SOC, and the motor speed, a fuzzy logic control strategy (FLC is applied to adjust the regenerative braking torque dynamically. In order to evaluate the performance of the cooperative braking control strategy, the braking system model of a hybrid electric vehicle is built in MATLAB/SIMULINK. It is found from the simulation that the cooperative braking control strategy suggested in this paper provides satisfactory braking performance, passenger comfort, and high regenerative efficiency.

Cell therapy worldwide: an incipient revolution.

Science.gov (United States)

Rao, Mahendra; Mason, Chris; Solomon, Susan

2015-01-01

The regenerative medicine field is large, diverse and active worldwide. A variety of different organizational and product models have been successful, and pioneering entrepreneurs have shown both what can work and, critically, what does not. Evolving regulations, novel funding mechanisms combined with new technological breakthroughs are keeping the field in a state of flux. The field struggles to cope with the lack of infrastructure and investment, it nevertheless has evolved from its roots in human stem cell therapy and tissue and organ transplants to a field composed of a variety of products from multiple cell sources with approval for use in numerous countries. Currently, tens of thousands of patients have been treated with some kind of cell therapy.

The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine.

Science.gov (United States)

Kiani, Mehrdad T; Higgins, Claire A; Almquist, Benjamin D

2018-04-09

The hair follicle is one of only two structures within the adult body that selectively degenerates and regenerates, making it an intriguing organ to study and use for regenerative medicine. Hair follicles have been shown to influence wound healing, angiogenesis, neurogenesis, and harbor distinct populations of stem cells; this has led to cells from the follicle being used in clinical trials for tendinosis and chronic ulcers. In addition, keratin produced by the follicle in the form of a hair fiber provides an abundant source of biomaterials for regenerative medicine. In this review, we provide an overview of the structure of a hair follicle, explain the role of the follicle in regulating the microenvironment of skin and the impact on wound healing, explore individual cell types of interest for regenerative medicine, and cover several applications of keratin-based biomaterials.

Cooperative Control of Regenerative Braking and Antilock Braking for a Hybrid Electric Vehicle

OpenAIRE

Yin, Guodong; Jin, XianJian

2013-01-01

A new cooperative braking control strategy (CBCS) is proposed for a parallel hybrid electric vehicle (HEV) with both a regenerative braking system and an antilock braking system (ABS) to achieve improved braking performance and energy regeneration. The braking system of the vehicle is based on a new method of HEV braking torque distribution that makes the antilock braking system work together with the regenerative braking system harmoniously. In the cooperative braking control strategy, a sli...

Understanding Translation

DEFF Research Database (Denmark)

Schjoldager, Anne Gram; Gottlieb, Henrik; Klitgård, Ida

Understanding Translation is designed as a textbook for courses on the theory and practice of translation in general and of particular types of translation - such as interpreting, screen translation and literary translation. The aim of the book is to help you gain an in-depth understanding...... of the phenomenon of translation and to provide you with a conceptual framework for the analysis of various aspects of professional translation. Intended readers are students of translation and languages, but the book will also be relevant for others who are interested in the theory and practice of translation...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

Results after replantation of avulsed permanent teeth. II. Periodontal healing and the role of physiologic storage and antiresorptive-regenerative therapy.

Science.gov (United States)

Pohl, Yango; Filippi, Andreas; Kirschner, Horst

2005-04-01

The status of the periodontal ligament (PDL) and of the pulp are decisive for the healing of avulsed and replanted teeth. A tooth rescue box was developed and distributed to offer optimal storage conditions for avulsed teeth. The therapy comprised extraoral endodontic treatment and applications of medicaments to enhance periodontal healing. In this long-term clinical study the healing results following avulsion and replantation were investigated. Twenty-eight permanent teeth in 24 patients were evaluated. The extraoral storage media and periods varied considerably. Soon after avulsion six teeth were stored in a cell culture medium (tooth rescue box Dentosafe) for 1-53 h; the PDL was defined as not compromised. Sixteen teeth were stored in a non-physiologic situation temporarily, the PDL was considered as compromised. Six teeth were stored in non-physiologic conditions for longer periods; the condition of the PDL was defined as hopeless. On 14 teeth antiresorptive-regenerative therapy (ART) with the local application of glucocorticoids and enamel matrix derivative and the systemic administration of doxycyclin was used. In all teeth extraoral endodontic treatment by retrograde insertion of posts was performed. The mean observation period was 31.2 months (+/-24.1; 5.1-100.2; median: 23.8). All six teeth rescued physiologically healed with a functional PDL (functional healing, FH) irrespective of the storage period. Of eight teeth with a compromised PDL on which ART was used, three teeth healed with a functional PDL. All other teeth showed replacement resorption, in three teeth additionally infection-related resorption was recorded. The predominant influence on the healing results was the immediate physiologic rescue of avulsed teeth (chi-square, P = 0.0001). The use of ART seemed to support FH (chi-square, P = 0.0547) in teeth with a compromised PDL. No other factors (maturity of roots, crown fractures, gender, age, antibiotics) were related to healing. In a linear

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

Science.gov (United States)

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. © AlphaMed Press.

Use of photoactivated disinfection and platelet-rich fibrin in regenerative Endodontics

Science.gov (United States)

Johns, Dexton Antony; Shivashankar, Vasundara Yayathi; Krishnamma, Shoba; Johns, Manu

2014-01-01

Aim: Photoactivated disinfection has been used as an adjunct to conventional endodontic treatment. Its use in regenerative endodontics is not reported in literature. The aim of this case report was to describe a new proposal for pulp revascularization with disinfection of pulp canal space using a unique combination of a photosensitizer solution and low-power laser light. Materials and Methods: A 9-year-old boy came with the chief complaint of discolored upper central incisors (#8, #9). A diagnosis of pulp necrosis was made on the basis of clinical and radiographic findings. The canal was irrigated with 5.25% sodium hypochlorite solution and dried with paper points. Photodynamic therapy was used to disinfect the root canal and platelet-rich fibrin was used to revitalize the pulp. Three millimeters of gray mineral trioxide aggregate was placed directly over the platelet-rich plasma clot. Three days later, the tooth was double-sealed with permanent filling materials. Results: Clinical examination revealed no sensitivity to percussion or palpation tests. Radiograph revealed continued thickening of the dentinal walls, root lengthening, regression of the peri-apical lesion and apical closure. Both the roots showed complete apical closure at the 10-month follow-up. However, the teeth were not responsive to electric pulp test. Conclusion: This report of pulp revascularization shows that disinfection with photodynamic therapy combined with platelet-rich fibrin leads to satisfactory root development in necrotic immature teeth. PMID:25298655

STUDY ON ENERGY EXCHANGE PROCESSES IN NORMAL OPERATION OF METRO ROLLING STOCK WITH REGENERATIVE BRAKING SYSTEMS

Directory of Open Access Journals (Sweden)

A. O. Sulym

2017-10-01

Full Text Available Purpose. The analysis of the existing studies showed that the increasing of energy efficiency of metro rolling stock becomes especially important and requires timely solutions. It is known that the implementation of regenerative braking systems on rolling stock will allow significantly solving this problem. It was proved that one of the key issues regarding the introduction of the above-mentioned systems is research on efficient use of electric energy of regenerative braking. The purpose of the work is to evaluate the amount of excessive electric power of regenerative braking under normal operation conditions of the rolling stock with regenerative braking systems for the analysis of the energy saving reserves. Methodology. Quantifiable values of electrical energy consumed for traction, returned to the contact line and dissipated in braking resistors (excessive energy are determined using results of experimental studies of energy exchange processes under normal operating conditions of metro rolling stock with regenerative systems. Statistical methods of data processing were applied as well. Findings. Results of the studies analysis of metro rolling stock operation under specified conditions in Sviatoshinsko-Brovarskaia line of KP «Kyiv Metro system» stipulate the following: 1 introduction of regenerative braking systems into the rolling stock allows to return about 17.9-23.2% of electrical energy consumed for traction to the contact line; 2 there are reserves for improving of energy efficiency of rolling stock with regenerative systems at the level of 20.2–29.9 % of electrical energy consumed for traction. Originality. For the first time, it is proved that the most significant factor that influences the quantifiable values of the electrical energy regeneration is a track profile. It is suggested to use coefficients which indicate the amount and reserves of unused (excessive electrical energy for quantitative evaluation. Studies on

Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening

OpenAIRE

Sharma, Arun; Wu, Joseph C; Wu, Sean M

2013-01-01

Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scienti...

Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

Science.gov (United States)

Connell, John J; Patrick, P Stephen; Yu, Yichao; Lythgoe, Mark F; Kalber, Tammy L

2015-01-01

Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

Mesenchymal stem cell therapy for laryngotracheal stenosis

DEFF Research Database (Denmark)

Jakobsen, Kathrine Kronberg; Grønhøj, Christian; Jensen, David H

2017-01-01

studies addressing the effect of MSC therapy on the airway. We assessed effect on inflammation, fibrosis, and MSC as a component in tissue engineering for treating defects in the airway. RESULTS: We identified eleven studies (n = 256 animals) from eight countries evaluating the effect of MSCs......BACKGROUND: Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown...... promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways. METHODS: PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980-January 2017 with the purpose of identifying all...

Mesenchymal Stem Cell Based Therapy for Prostate Cancer

Science.gov (United States)

2015-11-01

Montero-Menei, C.; Menei, P. Mesenchymal Stem Cells as Cellular Vehicles for Delivery of Nanoparticles to Brain Tumors. Biomaterials 2010, 31, 8393... Stem Cells : Considerations for Regenerative Medicine Approaches. Tissue Eng. Part B. Rev. 2010, 16, 159–168. 55. Ellem, S. J.; Taylor, R. a.; Furic, L...Award Number: W81XWH-13-1-0304 TITLE: Mesenchymal Stem Cell -Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs CONTRACTING

Performance Analysis of Regenerative Braking in Permanent Magnet Synchronous Motor Drives

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Andrew Adib

2018-02-01

Full Text Available This paper describes the design and analysis of a regenerative braking system for a permanent magnet synchronous motor (PMSM drive for electric vehicle (EV applications. First studied is the principle for electric braking control of a PMSM motor under field-oriented control (FOC. Next, the maximum braking torque in the regeneration mode as well as the braking torque for the maximum regeneration power, respectively, are deduced. Additionally, an optimum switching scheme for the inverter is developed with the objective of maximizing energy recovery during regenerative braking to the DC-bus capacitor. The integration of an ultra-capacitor module with the battery allows for the efficient and high power transfer under regenerative braking. It was important to manage the power flow to the DC-bus as this is a key issue that affects the efficiency of the overall system. Finally, the amounts of braking energy that can be recovered, and the efficiency with which it can be returned to the battery/ultra-capacitor, is analyzed for a PMSM coupled with a DC motor as the load. The results of the analysis are validated through experimentation.

Regenerative braking strategies, vehicle safety and stability control systems: critical use-case proposals

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Oleksowicz, Selim A.; Burnham, Keith J.; Southgate, Adam; McCoy, Chris; Waite, Gary; Hardwick, Graham; Harrington, Cian; McMurran, Ross

2013-05-01

The sustainable development of vehicle propulsion systems that have mainly focused on reduction of fuel consumption (i.e. CO2 emission) has led, not only to the development of systems connected with combustion processes but also to legislation and testing procedures. In recent years, the low carbon policy has made hybrid vehicles and fully electric vehicles (H/EVs) popular. The main virtue of these propulsion systems is their ability to restore some of the expended energy from kinetic movement, e.g. the braking process. Consequently new research and testing methods for H/EVs are currently being developed. This especially concerns the critical 'use-cases' for functionality tests within dynamic events for both virtual simulations, as well as real-time road tests. The use-case for conventional vehicles for numerical simulations and road tests are well established. However, the wide variety of tests and their great number (close to a thousand) creates a need for selection, in the first place, and the creation of critical use-cases suitable for testing H/EVs in both virtual and real-world environments. It is known that a marginal improvement in the regenerative braking ratio can significantly improve the vehicle range and, therefore, the economic cost of its operation. In modern vehicles, vehicle dynamics control systems play the principal role in safety, comfort and economic operation. Unfortunately, however, the existing standard road test scenarios are insufficient for H/EVs. Sector knowledge suggests that there are currently no agreed tests scenarios to fully investigate the effects of brake blending between conventional and regenerative braking as well as the regenerative braking interaction with active driving safety systems (ADSS). The paper presents seven manoeuvres, which are considered to be suitable and highly informative for the development and examination of H/EVs with regenerative braking capability. The critical manoeuvres presented are considered to be

PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.

Science.gov (United States)

Hsu, Jessie Hao-Ru; Hubbell-Engler, Benjamin; Adelmant, Guillaume; Huang, Jialiang; Joyce, Cailin E; Vazquez, Francisca; Weir, Barbara A; Montgomery, Philip; Tsherniak, Aviad; Giacomelli, Andrew O; Perry, Jennifer A; Trowbridge, Jennifer; Fujiwara, Yuko; Cowley, Glenn S; Xie, Huafeng; Kim, Woojin; Novina, Carl D; Hahn, William C; Marto, Jarrod A; Orkin, Stuart H

2017-09-01