WorldWideScience

Sample records for translate regenerative therapies

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

    OpenAIRE

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

    2015-01-01

    Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in...

  2. [Translational/regulatory science researches of NIHS for regenerative medicine and cellular therapy products].

    Science.gov (United States)

    Sato, Yoji

    2014-01-01

    In 2013, the Japanese Diet passed the Regenerative Medicine Promotion Act and the revisions to the Pharmaceutical Affairs Act, which was also renamed as the Therapeutic Products Act (TPA). One of the aims of the new/revised Acts is to promote the development and translation of and access to regenerative/cellular therapies. In the TPA, a product derived from processing cells is categorized as a subgroup of "regenerative medicine, cellular therapy and gene therapy products" (RCGPs), products distinct from pharmaceuticals and medical devices, allowing RCGPs to obtain a conditional and time- limited marketing authorization much earlier than that under the conventional system. To foster not only RCGPs, but also innovative pharmaceuticals and medical devices, the Ministry of Health, Labour and Welfare recently launched Translational Research Program for Innovative Pharmaceuticals, Medical Devices and RCGPs. This mini-review introduces contributions of the National Institute of Health Sciences (NIHS) to research projects on RCGPs in the Program.

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

    Science.gov (United States)

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

    2015-11-01

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

  4. Translating stem cell therapies: the role of companion animals in regenerative medicine

    OpenAIRE

    Volk, Susan W.; Theoret, Christine

    2013-01-01

    Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell r...

  5. Regenerative Endodontics: Barriers and Strategies for Clinical Translation

    OpenAIRE

    Kim, Sahng G.; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y.; Yang, Rujing; Zhou, Xuedong; Mao, Jeremy J.

    2012-01-01

    Despite a great deal of enthusiasm and effort, regenerative endodontics has encountered substantial challenges towards clinical translation. Recent adoption by the American Dental Association (ADA) of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for the majority of endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other orga...

  6. Regenerative endodontics: barriers and strategies for clinical translation.

    Science.gov (United States)

    Mao, Jeremy J; Kim, Sahng G; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y; Yang, Rujing; Zhou, Xuedong

    2012-07-01

    Regenerative endodontics has encountered substantial challenges toward clinical translation. The adoption by the American Dental Association of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for most endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Translating Regenerative Biomaterials Into Clinical Practice.

    Science.gov (United States)

    Stace, Edward T; Dakin, Stephanie G; Mouthuy, Pierre-Alexis; Carr, Andrew J

    2016-01-01

    Globally health care spending is increasing unsustainably. This is especially true of the treatment of musculoskeletal (MSK) disease where in the United States the MSK disease burden has doubled over the last 15 years. With an aging and increasingly obese population, the surge in MSK related spending is only set to worsen. Despite increased funding, research and attention to this pressing health need, little progress has been made toward novel therapies. Tissue engineering and regenerative medicine (TERM) strategies could provide the solutions required to mitigate this mounting burden. Biomaterial-based treatments in particular present a promising field of potentially cost-effective therapies. However, the translation of a scientific development to a successful treatment is fraught with difficulties. These barriers have so far limited translation of TERM science into clinical treatments. It is crucial for primary researchers to be aware of the barriers currently restricting the progression of science to treatments. Researchers need to act prospectively to ensure the clinical, financial, and regulatory hurdles which seem so far removed from laboratory science do not stall or prevent the subsequent translation of their idea into a treatment. The aim of this review is to explore the development and translation of new treatments. Increasing the understanding of these complexities and barriers among primary researchers could enhance the efficiency of biomaterial translation. © 2015 Wiley Periodicals, Inc.

  8. Regenerative Therapy for Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Narsis Daftarian

    2010-01-01

    Full Text Available Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.

  9. 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.

  10. Regenerative Rehabilitation: Combining Stem Cell Therapies and Activity-Dependent Stimulation.

    Science.gov (United States)

    Moritz, Chet T; Ambrosio, Fabrisia

    2017-07-01

    The number of clinical trials in regenerative medicine is burgeoning, and stem cell/tissue engineering technologies hold the possibility of becoming the standard of care for a multitude of diseases and injuries. Advances in regenerative biology reveal novel molecular and cellular targets, with potential to optimize tissue healing and functional recovery, thereby refining rehabilitation clinical practice. The purpose of this review is to (1) highlight the potential for synergy between the fields of regenerative medicine and rehabilitation, a convergence of disciplines known as regenerative rehabilitation; (2) provide translational examples of regenerative rehabilitation within the context of neuromuscular injuries and diseases; and (3) offer recommendations for ways to leverage activity dependence via combined therapy and technology, with the goal of enhancing long-term recovery. The potential clinical benefits of regenerative rehabilitation will likely become a critical aspect in the standard of care for many neurological and musculoskeletal disorders.

  11. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

  12. 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.

  13. Platelet rich fibrin - a novel acumen into regenerative endodontic therapy

    Directory of Open Access Journals (Sweden)

    Kavita Hotwani

    2014-02-01

    Full Text Available Research into regenerative dentistry has added impetus onto the field of molecular biology. It can be documented as a prototype shift in the therapeutic armamentarium for dental disease. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. A new family of platelet concentrates called the platelet rich fibrin (PRF has been recently used by several investigators and has shown application in diverse disciplines of dentistry. This paper is intended to add light on the various prospects of PRF and clinical insights to regenerative endodontic therapy.

  14. Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies

    Science.gov (United States)

    Scarfe, Lauren; Brillant, Nathalie; Kumar, J. Dinesh; Ali, Noura; Alrumayh, Ahmed; Amali, Mohammed; Barbellion, Stephane; Jones, Vendula; Niemeijer, Marije; Potdevin, Sophie; Roussignol, Gautier; Vaganov, Anatoly; Barbaric, Ivana; Barrow, Michael; Burton, Neal C.; Connell, John; Dazzi, Francesco; Edsbagge, Josefina; French, Neil S.; Holder, Julie; Hutchinson, Claire; Jones, David R.; Kalber, Tammy; Lovatt, Cerys; Lythgoe, Mark F.; Patel, Sara; Patrick, P. Stephen; Piner, Jacqueline; Reinhardt, Jens; Ricci, Emanuelle; Sidaway, James; Stacey, Glyn N.; Starkey Lewis, Philip J.; Sullivan, Gareth; Taylor, Arthur; Wilm, Bettina; Poptani, Harish; Murray, Patricia; Goldring, Chris E. P.; Park, B. Kevin

    2017-10-01

    Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.

  15. 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.

  16. Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

    Science.gov (United States)

    Marei, Mona K.; El Backly, Rania M.

    2018-01-01

    Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such “replacement therapies” appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use. PMID:29770323

  17. Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

    Directory of Open Access Journals (Sweden)

    Mona K. Marei

    2018-05-01

    Full Text Available Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such “replacement therapies” appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use.

  18. 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

  19. Tissue Engineering in Regenerative Dental Therapy

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2016-07-01

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

  1. 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.

  2. 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.

  3. Regenerative dentistry: translating advancements in basic science research to the dental practice.

    Science.gov (United States)

    Garcia-Godoy, Franklin; Murray, Peter

    2010-01-01

    Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue engineering, molecular biology and the human genome project provide the basis for the introduction of new technologies into dentistry. This review provides an assessment of how tissue engineering, stem cell, genetic transfer, biomaterial and growth factor therapies can be integrated into clinical dental therapies to restore and regenerate oral tissues. In parallel to the creation of a new field in general medicine called "regenerative medicine," we call this field "regenerative dentistry." While the problems of introducing regenerative therapies are substantial, the potential benefits to patients and the profession are equally ground-breaking. In this review, we outline a few areas of interest for the future of oral and dental medicine in which advancements in basic science have already been adapted to fit the goals of 21st century dentistry.

  4. 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

  5. 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

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

    Science.gov (United States)

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

    2014-08-01

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

  7. 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.

  8. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

    Science.gov (United States)

    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

  13. 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...

  14. 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

  15. 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.

  16. 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.

  17. Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue.

    Science.gov (United States)

    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.

  18. Regenerative Medicine Build-Out

    Science.gov (United States)

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

    2015-01-01

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

  19. Regenerative Medicine Build-Out.

    Science.gov (United States)

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

    2015-12-01

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

  20. 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.

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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,

  8. Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design.

    Science.gov (United States)

    Bartunek, Jozef; Davison, Beth; Sherman, Warren; Povsic, Thomas; Henry, Timothy D; Gersh, Bernard; Metra, Marco; Filippatos, Gerasimos; Hajjar, Roger; Behfar, Atta; Homsy, Christian; Cotter, Gad; Wijns, William; Tendera, Michal; Terzic, Andre

    2016-02-01

    Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months. The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF. NCT01768702. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Phenylketonuria: translating research into novel therapies

    Science.gov (United States)

    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

  16. 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.

  17. 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.

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

    Science.gov (United States)

    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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. [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

  14. 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.

  15. 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

  16. 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.

  17. 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

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

    Science.gov (United States)

    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

  19. 78 FR 43889 - Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine...

    Science.gov (United States)

    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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. The regenerative medicine coalition. Interview with Frank-Roman Lauter.

    Science.gov (United States)

    Lauter, Frank-Roman

    2012-11-01

    Frank-Roman Lauter, Secretary General of the recently launched Regenerative Medicine Coalition, explains how the coalition was formed and what they hope to achieve. Frank-Roman Lauter has served as Secretary General of the Regenerative Medicine Coalition since 2012, and as Head of Business Development at Berlin-Brandenburg Center for Regenerative Therapies since 2007. Frank-Roman Lauter's interest is the organization of academic infrastructures to promote efficient translation of research findings into new therapies. He co-organizes joined strategy development for regenerative medicine clusters from seven European countries (FP7-EU Project) and has initiated cooperation between the California Institute for Regenerative Medicine and the German Federal Ministry for Education & Research, resulting in a joined funding program. Recently, he cofounded the international consortium of Regenerative Medicine translational centers (RMC; www.the-rmc.org ). Trained as a molecular biologist at the Max-Planck Institute in Berlin-Dahlem and at Stanford, he has 16 years of experience as an entrepreneur and life science manager in Germany and the USA.

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

    Science.gov (United States)

    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.

  9. 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...

  10. The interplay of post-translational modification and gene therapy

    Directory of Open Access Journals (Sweden)

    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

  11. 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

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Heart Cells with Regenerative Potential from Pediatric Patients with End Stage Heart Failure: A Translatable Method to Enrich and Propagate

    Directory of Open Access Journals (Sweden)

    Ann Steele

    2012-01-01

    Full Text Available Background. Human cardiac-derived progenitor cells (hCPCs have shown promise in treating heart failure (HF in adults. The purpose of this study was to describe derivation of hCPCs from pediatric patients with end-stage HF. Methods. At surgery, discarded right atrial tissues (hAA were obtained from HF patients (n=25; hAA-CHF. Minced tissues were suspended in complete (serum-containing DMEM. Cells were selected for their tissue migration and expression of stem cell factor receptor (hc-kit. Characterization of hc-kitpositive cells included immunohistochemical screening with a panel of monoclonal antibodies. Results. Cells, including phase-bright cells identified as hc-kitpositive, spontaneously emigrated from hAA-CHF in suspended explant cultures (SEC after Day 7. When cocultured with tissue, emigrated hc-kitpositive cells proliferated, first as loosely attached clones and later as multicellular clusters. At Day 21~5% of cells were hc-kitpositive. Between Days 14 and 28 hc-kitpositive cells exhibited mesodermal commitment (GATA-4positive and NKX2.5positive; then after Day 28 cardiac lineages (flk-1positive, smooth muscle actinpositive, troponin-Ipositive, and myosin light chainpositive. Conclusions. C-kitpositive hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kitpositive cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro.

  20. 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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    Science.gov (United States)

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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.

  10. Amniotic fluid stem cells: a promising therapeutic resource for cell-based regenerative therapy.

    Science.gov (United States)

    Antonucci, Ivana; Pantalone, Andrea; Tete, Stefano; Salini, Vincenzo; Borlongan, Cesar V; Hess, David; Stuppia, Liborio

    2012-01-01

    Stem cells have been proposed as a powerful tool in the treatment of several human diseases, both for their ability to represent a source of new cells to replace those lost due to tissue injuries or degenerative diseases, and for the ability of produce trophic molecules able to minimize damage and promote recovery in the injured tissue. Different cell types, such as embryonic, fetal or adult stem cells, human fetal tissues and genetically engineered cell lines, have been tested for their ability to replace damaged cells and to restore the tissue function after transplantation. Amniotic fluid -derived Stem cells (AFS) are considered a novel resource for cell transplantation therapy, due to their high renewal capacity, the "in vitro" expression of embryonic cell lineage markers, and the ability to differentiate in tissues derived from all the three embryonic layers. Moreover, AFS do not produce teratomas when transplanted into animals and are characterized by a low antigenicity, which could represent an advantage for cell transplantation or cell replacement therapy. The present review focuses on the biological features of AFS, and on their potential use in the treatment of pathological conditions such as ischemic brain injury and bone damages.

  11. 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

  12. Regenerative endodontics.

    Science.gov (United States)

    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.

  13. 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.

  14. Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

    Directory of Open Access Journals (Sweden)

    Umashankar A

    2016-04-01

    Full Text Available Abhishek Umashankar,1,2,* Mandi J Corenblum,1,* Sneha Ray,1,2,* Michel Valdez,3 Eriko S Yoshimaru,3 Theodore P Trouard,3,4 Lalitha Madhavan1,4 1Department of Neurology, 2Neuroscience and Cognitive Science Undergraduate Program, Undergraduate Biology Research Program, 3Department of Biomedical Engineering, 4Evelyn F McKnight Brain Institute, University of Arizona, Tucson, AZ, USA *These authors contributed equally to this work Abstract: An essential component of developing successful neural stem cell (NSC-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI. However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB, which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 µg/mL were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 µg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 µg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the

  15. Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation.

    Science.gov (United States)

    Umashankar, Abhishek; Corenblum, Mandi J; Ray, Sneha; Valdez, Michel; Yoshimaru, Eriko S; Trouard, Theodore P; Madhavan, Lalitha

    2016-01-01

    An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 μg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 μg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 μg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 μg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68(+)-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an

  16. 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.

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

    Science.gov (United States)

    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.

  18. 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.

  19. Targeting post-translational modifications of histones for cancer therapy.

    Science.gov (United States)

    Hsu, Y-C; Hsieh, Y-H; Liao, C-C; Chong, L-W; Lee, C-Y; Yu, Y-L; Chou, R-H

    2015-10-30

    Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

  20. Imaging: Guiding the Clinical Translation of Cardiac Stem Cell Therapy

    Science.gov (United States)

    Nguyen, Patricia K.; Lan, Feng; Wang, Yongming; Wu, Joseph C.

    2011-01-01

    Stem cells have been touted as the holy grail of medical therapy with promises to regenerate cardiac tissue, but it appears the jury is still out on this novel therapy. Using advanced imaging technology, scientists have discovered that these cells do not survive nor engraft long-term. In addition, only marginal benefit has been observed in large animal studies and human trials. However, all is not lost. Further application of advanced imaging technology will help scientists unravel the mysteries of stem cell therapy and address the clinical hurdles facing its routine implementation. In this review, we will discuss how advanced imaging technology will help investigators better define the optimal delivery method, improve survival and engraftment, and evaluate efficacy and safety. Insights gained from this review may direct the development of future preclinical investigations and clinical trials. PMID:21960727

  1. An invention of thermo-responsive polymer surface, yielding cell sheet based regenerative therapies in cardiology and ophthalmology

    Directory of Open Access Journals (Sweden)

    Sawa Y

    2015-12-01

    /2009/091/000590 after standardizing the procedures for collection of autologous bone marrow cells in January 2010. Out of the 104 patients, 68 patients met the inclusion criteria for the trial follow up. Of the total, 45 patients could not be followed up in spite of the team’s best efforts to trace them. Only 23 patients (34% were available for follow up. Amongst those, 19 patients (82.6% were alive at the end of the first year and 10 out of the 19 patients (52.6% had at least a 5% increase in the Ejection Fraction post therapy and had significant improvement in the functional status. The procedure was safe in all the other patients which were similar to the results of other studies reported so far. Though the results of this clinical trial infer that stem cells are not an alternative to heart transplantation they offer a 'dynamic cellular support' for regenerating functional and viable myocardium. As a step further in identifying definitive cell based therapy approaches to treat heart failure, cell sheet therapy was advocated by Prof. Sawa’s team. In Prof. Sawa’s Institute, longitudinal research team was launched in the late 1990s to develop new treatments for advanced cardiac disease by an array of basic experimental studies of surgical and regenerative approaches. As a result, placement of autologous or allogeneic stem/progenitor cell-sheets over the cardiac surface via surgical approach was proven to be the most safe and efficacious treatment for advanced cardiac failure. To grow the skeletal myoblasts as a sheet for clinical transplantation, Prof. Sawa’s team employed the thermo-responsive polymer dish developed by Prof. Okano’s team which enabled the in vitro growth of the skeletal myoblasts as patches and their easy separation for application over the ischemic/infarcted area of the heart after thorough validation in animal experiments [4]. A clinical study was, therefore, launched in 2006, wherein autologous skeletal myoblast cell-sheets were directly

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

    Science.gov (United States)

    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

  3. Denosumab for bone diseases: translating bone biology into targeted therapy.

    Science.gov (United States)

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  4. Translational aspects of cell therapy for heart failure

    OpenAIRE

    Nasseri, Boris

    2015-01-01

    This cumulative “habilitation” thesis focuses on myocardial regeneration by means of cell therapy and on experimental and clinical approaches. To supplement the articles published by the author the work gives an overview of the pathogenesis of heart failure and remodeling of the heart, taking into account the role of nitric oxide and statins. Further, the treatment of ischemic heart failure including organ transplantation and mechanical circulatory support is discussed. Different approaches t...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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.

  7. 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

  8. 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…

  9. Interview: commercial translation of cell-based therapies and regenerative medicine: learning by experience. Interview by Emily Culme-Seymour.

    Science.gov (United States)

    Haseltine, William A

    2011-07-01

    Dr Haseltine speaks to Emily Culme-Seymour, Assistant Commissioning Editor William A Haseltine, PhD has an active career in both Science and Business. He was a professor at Harvard Medical School and Harvard School of Public Health (MA, USA) from 1976 to 1993, where he was Founder and Chair of two academic research departments. He is well known for his pioneering work on cancer, HIV/AIDS and genomics. He has authored more than 200 manuscripts in peer-reviewed journals and is the author of several books. He is the founder of Human Genome Sciences, Inc. and served as the Chairman and CEO of the company until 2004. He is also the founder of several other successful biotechnology companies. William Haseltine is currently Chairman and President of ACCESS Health International, Inc., which supports access to affordable, high-quality health services in low, middle and high income countries, and Chairman of the Haseltine Foundation for Science and the Arts, which fosters a dialog between sciences and the arts. He is an Adjunct Professor at the Scripps Institute for Medical Research and the Institute of Chemical Engineering, the University of Mumbai, India. He is a member of the Advisory Board of the IE University, Madrid, the President's Council of the Cold Spring Harbor Laboratory, the Advisory Council for the Koch Institute of MIT, a member of the University Council Committee on technology transfer, Yale University, and is a Lifetime Governor of the New York Academy of Science (NY, USA). He is an honorary member of the Board of Trustees of the Brookings Institution, a member of the Board of Trustees of the Center for Emerging Markets of the Indian School of Business, a member of the Council on Foreign Relations, a member of the Board of AID for AIDS International, and a member of the Chairman's Circle of the Asia Society. He is a member of the Advisory Board of the Metropolitan Opera (NY, USA), the Chairman's Council of the Metropolitan Museum (NY, USA), the International Council of the Guggenheim Museum, the International Council of the Tate Modern, the Board of Directors of the Young Concert Artists, Inc. and the Youth Orchestra of the Americas.

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

    International Nuclear Information System (INIS)

    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)

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Recent considerations in regenerative endodontic treatment approaches

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    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.

  17. 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.

  18. 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.

  19. 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

  20. Stress urinary incontinence animal models as a tool to study cell-based regenerative therapies targeting the urethral sphincter.

    Science.gov (United States)

    Herrera-Imbroda, Bernardo; Lara, María F; Izeta, Ander; Sievert, Karl-Dietrich; Hart, Melanie L

    2015-03-01

    Urinary incontinence (UI) is a major health problem causing a significant social and economic impact affecting more than 200million people (women and men) worldwide. Over the past few years researchers have been investigating cell therapy as a promising approach for the treatment of stress urinary incontinence (SUI) since such an approach may improve the function of a weakened sphincter. Currently, a diverse collection of SUI animal models is available. We describe the features of the different models of SUI/urethral dysfunction and the pros and cons of these animal models in regard to cell therapy applications. We also discuss different cell therapy approaches and cell types tested in preclinical animal models. Finally, we propose new research approaches and perspectives to ensure the use of cellular therapy becomes a real treatment option for SUI. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective.

    Science.gov (United States)

    Takagi, Toshinori; Yoshimura, Shinichi; Sakuma, Rika; Nakano-Doi, Akiko; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-12-01

    Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.

  17. 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).

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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 ...

  3. Dental pulp stem cells in regenerative dentistry.

    Science.gov (United States)

    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.

  4. Regenerative endodontics: A way forward.

    Science.gov (United States)

    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.

  5. 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.

  6. Regenerative Hydride Heat Pump

    Science.gov (United States)

    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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Microscale Regenerative Heat Exchanger

    Science.gov (United States)

    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.

  17. 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.....

  18. 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

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

    Science.gov (United States)

    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.

  20. 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.

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

    Science.gov (United States)

    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.

  2. 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.

  3. Introduction to regenerative medicine and tissue engineering.

    Science.gov (United States)

    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.

  4. 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.

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. Regenerative Medicine for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    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.

  7. Regenerative nanotechnology in oral and maxillofacial surgery.

    Science.gov (United States)

    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.

  8. 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...

  9. 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.

  10. 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.

  11. Center for Neuroscience & Regenerative Medicine

    Data.gov (United States)

    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...

  12. 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.

  13. 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

  14. 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.)

  15. 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.

  16. 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.

  17. 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

    2017-03-01

    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

  18. 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

  19. Regenerative endodontics: A state of the art

    Directory of Open Access Journals (Sweden)

    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.

  20. Regenerative Endodontics: A Road Less Travelled

    Science.gov (United States)

    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

  1. Immuno-Oncology-The Translational Runway for Gene Therapy: Gene Therapeutics to Address Multiple Immune Targets.

    Science.gov (United States)

    Weß, Ludger; Schnieders, Frank

    2017-12-01

    Cancer therapy is once again experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing only single targets or pathways. Even the combination of several neo-antigens in cancer vaccines is not sufficient for successful, lasting tumor eradication. The focus has therefore shifted to the immune system's role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells. Immune processes, however, require novel concepts beyond the traditional "single-target-single drug" paradigm and need parallel targeting of diverse cells and mechanisms. This review gives a perspective on the role of gene therapy technologies in the evolving immuno-oncology space and identifies gene therapy as a major driver in the development and regulation of effective cancer immunotherapy. Present challenges and breakthroughs ranging from chimeric antigen receptor T-cell therapy, gene-modified oncolytic viruses, combination cancer vaccines, to RNA therapeutics are spotlighted. Gene therapy is recognized as the most prominent technology enabling effective immuno-oncology strategies.

  2. 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.

  3. Determine the Impact of Novel BRCA1 Translation Start Sites on Therapy Resistance in Ovarian Cancer

    Science.gov (United States)

    2017-09-01

    Award Number: W81XWH-15-1-0197 TITLE: PRINCIPAL INVESTIGATOR: Neil Johnson, Ph.D. CONTRACTING ORGANIZATION: Institute for Cancer Research...Therapy Resistance in Ovarian Cancer The views, opinions and/or findings contained in this report are those of the author(s) and should not be...Start Sites on Therapy 5b. GRANT NUMBER Resistance in Ovarian Cancer W81XWH-15-1-0197 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Neil

  4. Lost in translation? Moving contingency management and cognitive behavioral therapy into clinical practice.

    Science.gov (United States)

    Carroll, Kathleen M

    2014-10-01

    In the treatment of addictions, the gap between the availability of evidence-based therapies and their limited implementation in practice has not yet been bridged. Two empirically validated behavioral therapies, contingency management (CM) and cognitive behavioral therapy (CBT), exemplify this challenge. Both have a relatively strong level of empirical support but each has weak and uneven adoption in clinical practice. This review highlights examples of how barriers to their implementation in practice have been addressed systematically, using the Stage Model of Behavioral Therapies Development as an organizing framework. For CM, barriers such as cost and ideology have been addressed through the development of lower-cost and other adaptations to make it more community friendly. For CBT, barriers such as relative complexity, lack of trained providers, and need for supervision have been addressed via conversion to standardized computer-assisted versions that can serve as clinician extenders. Although these and other modifications have rendered both interventions more disseminable, diffusion of innovation remains a complex, often unpredictable process. The existing specialty addiction-treatment system may require significant reforms to fully implement CBT and CM, particularly greater focus on definable treatment goals and performance-based outcomes. © 2014 New York Academy of Sciences.

  5. 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

  6. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael; Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Weber, Randal S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kies, Merrill S. [Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lewin, Jan S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Palmer, Matthew B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-07-15

    Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

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

    Science.gov (United States)

    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.

  8. Cell Therapy in Organ Transplantation: Our Experience on the Clinical Translation of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Niloufar Safinia

    2018-02-01

    Full Text Available Solid organ transplantation is the treatment of choice for patients with end-stage organ dysfunction. Despite improvements in short-term outcome, long-term outcome is suboptimal due to the increased morbidity and mortality associated with the toxicity of immunosuppressive regimens and chronic rejection (1–5. As such, the attention of the transplant community has focused on the development of novel therapeutic strategies to achieve allograft tolerance, a state whereby the immune system of the recipient can be re-educated to accept the allograft, averting the need for long-term immunosuppression. Indeed, reports of “operational” tolerance, whereby the recipient is off all immunosuppressive drugs and maintaining good graft function, is well documented in the literature for both liver and kidney transplantations (6–8. However, this phenomenon is rare and in the setting of liver transplantation has been shown to occur late after transplantation, with the majority of patients maintained on life-long immunosupression to prevent allograft rejection (9. As such, significant research has focused on immune regulation in the context of organ transplantation with regulatory T cells (Tregs identified as cells holding considerable promise in this endeavor. This review will provide a brief introduction to human Tregs, their phenotypic and functional characterization and focuses on our experience to date at the clinical translation of Treg immunotherapy in the setting of solid organ transplantation.

  9. Translating tolerogenic therapies to the clinic – where do we stand?

    Directory of Open Access Journals (Sweden)

    Fadi eIssa

    2012-08-01

    Full Text Available Manipulation of the immune system to prevent the development of a specific immune response is an ideal strategy to improve outcomes after transplantation. A number of experimental techniques exploiting central and peripheral tolerance mechanisms have demonstrated success, leading to the first early phase clinical trials for tolerance induction. The first major strategy centres on the facilitation of donor-cell mixed chimerism in the transplant recipient with the use of bone marrow or haematopoietic stem cell transplantation. The second strategy, utilising peripheral regulatory mechanisms, focuses on cellular therapy with regulatory T cells. This review examines the key studies and novel research directions in the field of immunological tolerance.

  10. 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.

  11. Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke

    Directory of Open Access Journals (Sweden)

    Sun Chongran

    2010-08-01

    Full Text Available Abstract Background The relationship between functional improvements in ischemic rats given a neural stem cell (NSC transplant and the modulation of the class I major histocompatibility complex (MHC mediated by NSC-derived neurotrophins was investigated. Methods The levels of gene expression of nerve growth factor (NGF, brain-derived neurotropic factor (BDNF and neurotrophin-3 (NT-3 were assayed from cultures of cortical NSC from Sprague-Dawley rat E16 embryos. The levels of translated NGF in spent culture media from NSC cultures and the cerebral spinal fluid (CSF of rats with and without NGF injection or NSC transplant were also measured. Results We found a significant increase of NGF, BDNF and NT-3 transcripts and NGF proteins in both the NSC cultures and the CSF of the rats. The immunochemical staining for MHC in brain sections and the enzyme-linked immunosorbent assay of CSF were carried out in sham-operated rats and rats with surgically induced focal cerebral ischemia. These groups were further divided into animals that did and did not receive NGF administration or NSC transplant into the cisterna magna. Our results show an up-regulation of class I MHC in the ischemic rats with NGF and NSC administration. The extent of caspase-III immunoreactivity was comparable among three arms in the ischemic rats. Conclusion Readouts of somatosensory evoked potential and the trap channel test illustrated improvements in the neurological function of ischemic rats treated with NGF administration and NSC transplant.

  12. 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.

  13. Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation.

    Science.gov (United States)

    Prasanna, Pataje G S; Narayanan, Deepa; Hallett, Kory; Bernhard, Eric J; Ahmed, Mansoor M; Evans, Gregory; Vikram, Bhadrasain; Weingarten, Michael; Coleman, C Norman

    2015-09-01

    Although radiation therapy is an important cancer treatment modality, patients may experience adverse effects. The use of a radiation-effect modulator may help improve the outcome and health-related quality of life (HRQOL) of patients undergoing radiation therapy either by enhancing tumor cell killing or by protecting normal tissues. Historically, the successful translation of radiation-effect modulators to the clinic has been hindered due to the lack of focused collaboration between academia, pharmaceutical companies and the clinic, along with limited availability of support for such ventures. The U.S. Government has been developing medical countermeasures against accidental and intentional radiation exposures to mitigate the risk and/or severity of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposures (DEARE), and there is now a drug development pipeline established. Some of these medical countermeasures could potentially be repurposed for improving the outcome of radiation therapy and HRQOL of cancer patients. With the objective of developing radiation-effect modulators to improve radiotherapy, the Small Business Innovation Research (SBIR) Development Center at the National Cancer Institute (NCI), supported by the Radiation Research Program (RRP), provided funding to companies from 2011 to 2014 through the SBIR contracts mechanism. Although radiation-effect modulators collectively refer to radioprotectors, radiomitigators and radiosensitizers, the focus of this article is on radioprotection and mitigation of radiation injury. This specific SBIR contract opportunity strengthened existing partnerships and facilitated new collaborations between academia and industry. In this commentary, we assess the impact of this funding opportunity, outline the review process, highlight the organ/site-specific disease needs in the clinic for the development of radiation-effect modulators, provide a general understanding of a framework for gathering

  14. 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.

  15. 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.

  16. 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

  17. Why regenerative medicine needs an extracellular matrix.

    Science.gov (United States)

    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.

  18. 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.

  19. 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

  20. MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

    International Nuclear Information System (INIS)

    Yu, C.

    2015-01-01

    Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, and the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration

  1. MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C. [Univ Maryland School of Medicine (United States)

    2015-06-15

    Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, and the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration

  2. Temporomandibular Joint Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Xavier Van Bellinghen

    2018-02-01

    Full Text Available The temporomandibular joint (TMJ is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules. To succeed in functional and structural regeneration of TMJ is very challenging. Innovative strategies and biomaterials are absolutely crucial because TMJ can be considered as one of the most difficult tissues to regenerate due to its limited healing capacity, its unique histological and structural properties and the necessity for long-term prevention of its ossified or fibrous adhesions. The ideal approach for TMJ regeneration is a unique scaffold functionalized with an osteochondral molecular gradient containing a single stem cell population able to undergo osteogenic and chondrogenic differentiation such as BMSCs, ADSCs or DPSCs. The key for this complex regeneration is the functionalization with active molecules such as IGF-1, TGF-β1 or bFGF. This regeneration can be optimized by nano/micro-assisted functionalization and by spatiotemporal drug delivery systems orchestrating the 3D formation of TMJ tissues.

  3. A helium regenerative compressor

    International Nuclear Information System (INIS)

    Swift, W.L.; Nutt, W.E.; Sixsmith, H.

    1994-01-01

    This paper discusses the design and performance of a regenerative compressor that was developed primarily for use in cryogenic helium systems. The objectives for the development were to achieve acceptable efficiency in the machine using conventional motor and bearing technology while reducing the complexity of the system required to control contamination from the lubricants. A single stage compressor was built and tested. The compressor incorporates aerodynamically shaped blades on a 218 mm (8.6 inches) diameter impeller to achieve high efficiency. A gas-buffered non-contact shaft seal is used to oppose the diffusion of lubricant from the motor bearings into the cryogenic circuit. Since it is a rotating machine, the flow is continuous and steady, and the machine is very quiet. During performance testing with helium, the single stage machine has demonstrated a pressure ratio of 1.5 at a flow rate of 12 g/s with measured isothermal efficiencies in excess of 30%. This performance compares favorably with efficiencies generally achieved in oil flooded screw compressors

  4. Activating human genes with zinc finger proteins, transcription activator-like effectors and CRISPR/Cas9 for gene therapy and regenerative medicine.

    Science.gov (United States)

    Gersbach, Charles A; Perez-Pinera, Pablo

    2014-08-01

    New technologies have recently been developed to control the expression of human genes in their native genomic context by engineering synthetic transcription factors that can be targeted to any DNA sequence. The ability to precisely regulate any gene as it occurs naturally in the genome provides a means to address a variety of diseases and disorders. This approach also circumvents some of the traditional challenges of gene therapy. In this editorial, we review the technologies that have enabled targeted human gene activation, including the engineering of transcription factors based on zinc finger proteins, transcription activator-like effectors and the CRISPR/Cas9 system. Additionally, we highlight examples in which these methods have been developed for therapeutic applications and discuss challenges and opportunities.

  5. Promoting Translational Research Among Movement Science, Occupational Science, and Occupational Therapy.

    Science.gov (United States)

    Sainburg, Robert L; Liew, Sook-Lei; Frey, Scott H; Clark, Florence

    2017-01-01

    Integration of research in the fields of neural control of movement and biomechanics (collectively referred to as movement science) with the field of human occupation directly benefits both areas of study. Specifically, incorporating many of the quantitative scientific methods and analyses employed in movement science can help accelerate the development of rehabilitation-relevant research in occupational therapy (OT) and occupational science (OS). Reciprocally, OT and OS, which focus on the performance of everyday activities (occupations) to promote health and well-being, provide theoretical frameworks to guide research on the performance of actions in the context of social, psychological, and environmental factors. Given both fields' mutual interest in the study of movement as it relates to health and disease, the authors posit that combining OS and OT theories and principles with the theories and methods in movement science may lead to new, impactful, and clinically relevant knowledge. The first step is to ensure that individuals with OS or OT backgrounds are academically prepared to pursue advanced study in movement science. In this article, the authors propose 2 strategies to address this need.

  6. CGRP as the target of new migraine therapies - successful translation from bench to clinic.

    Science.gov (United States)

    Edvinsson, Lars; Haanes, Kristian Agmund; Warfvinge, Karin; Krause, Diana N

    2018-06-01

    Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these drugs come into clinical use, we provide an overview of knowledge that has led to successful development of these drugs. We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.

  7. 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.

  8. Translating Response During Therapy into Ultimate Treatment Outcome: A Personalized 4-Dimensional MRI Tumor Volumetric Regression Approach in Cervical Cancer

    International Nuclear Information System (INIS)

    Mayr, Nina A.; Wang, Jian Z.; Lo, Simon S.; Zhang Dongqing; Grecula, John C.; Lu Lanchun; Montebello, Joseph F.; Fowler, Jeffrey M.; Yuh, William T.C.

    2010-01-01

    Purpose: To assess individual volumetric tumor regression pattern in cervical cancer during therapy using serial four-dimensional MRI and to define the regression parameters' prognostic value validated with local control and survival correlation. Methods and Materials: One hundred and fifteen patients with Stage IB 2 -IVA cervical cancer treated with radiation therapy (RT) underwent serial MRI before (MRI 1) and during RT, at 2-2.5 weeks (MRI 2, at 20-25 Gy), and at 4-5 weeks (MRI 3, at 40-50 Gy). Eighty patients had a fourth MRI 1-2 months post-RT. Mean follow-up was 5.3 years. Tumor volume was measured by MRI-based three-dimensional volumetry, and plotted as dose(time)/volume regression curves. Volume regression parameters were correlated with local control, disease-specific, and overall survival. Results: Residual tumor volume, slope, and area under the regression curve correlated significantly with local control and survival. Residual volumes ≥20% at 40-50 Gy were independently associated with inferior 5-year local control (53% vs. 97%, p <0.001) and disease-specific survival rates (50% vs. 72%, p = 0.009) than smaller volumes. Patients with post-RT residual volumes ≥10% had 0% local control and 17% disease-specific survival, compared with 91% and 72% for <10% volume (p <0.001). Conclusion: Using more accurate four-dimensional volumetric regression analysis, tumor response can now be directly translated into individual patients' outcome for clinical application. Our results define two temporal thresholds critically influencing local control and survival. In patients with ≥20% residual volume at 40-50 Gy and ≥10% post-RT, the risk for local failure and death are so high that aggressive intervention may be warranted.

  9. Testing the validity of a translated pharmaceutical therapy-related quality of life instrument, using qualitative 'think aloud' methodology.

    Science.gov (United States)

    Renberg, T; Kettis Lindblad, A; Tully, M P

    2008-06-01

    In pharmacy practice, there is a need for valid and reliable instruments to study patient-reported outcomes. One potential candidate is a pharmaceutical therapy-related quality of life (PTRQoL) instrument. This study explored the face and content validity, including cognitive aspects of question answering of a PTRQoL instrument, translated from English to Swedish. A sample of 16 customers at Swedish community pharmacies, was asked to fill in the PTRQoL instrument while constantly reporting how they reasoned. The resulting interviews and concurrent probing, were audio-taped, transcribed verbatim and analysed using constant comparison method. The relation between the measurement and its theoretical underpinning was challenged. Respondents neglected to read the instructions, used response options in an unpredictable way, and varied in their interpretations of the items. The combination of 'think-aloud', retrospective probing and qualitative analysis informed on the validity of the PTRQoL instrument and was valuable in questionnaire development. The study also identified specific problems that could be relevant for other instruments probing patients' medicines-related attitudes and behaviour.

  10. Implementation of antiretroviral therapy guidelines for under-five children in Tanzania: translating recommendations into practice

    Science.gov (United States)

    Nuwagaba-Biribonwoha, Harriet; Wang, Chunhui; Kilama, Bonita; Jowhar, Farhat K; Antelman, Gretchen; Panya, Milembe F; Abrams, Elaine J

    2015-01-01

    Introduction Paediatric antiretroviral therapy (ART) guidelines have been updated several times in recent years. We assessed implementation of ART guidelines among under-five children to inform the transition to universal paediatric ART in Tanzania. Methods We conducted a retrospective cohort analysis of infants (0 to 11 months) and children (12 to 59 months) enrolled between 2010 and 2012 using routinely collected data. Infants and children were initiated on ART according to the 2008 World Health Organization (WHO) recommendations/2009 Tanzania guidelines (universal ART for infants). Cumulative ART initiation incidence and correlates of ART initiation were examined using competing risk methods accounting for attrition (death or loss to follow-up). Kaplan-Meier methods and Cox regression models were used to examine attrition on ART and its correlates. Results A total of 1679 children were enrolled at 69 clinics: 469 (28%) infants and 1210 (74%) children. Infant cumulative ART initiation incidence was 59.6, 71.3 and 78.0% at one, three and six months of follow-up. Infants were more likely to start ART if enrolled in 2012 [adjusted sub-hazard ratio (AsHR)=2.2, 95% confidence interval (CI): 1.7 to 2.8] or 2011 (AsHR=1.8, 95% CI: 1.4 to 2.3) compared to 2010; they were more likely to start ART from prevention of mother-to-child HIV transmission (AsHR=1.6, 95% CI: 1.3 to 2.1) and inpatient wards (AsHR=1.5, 95% CI: 1.2 to 2.0) versus being enrolled from voluntary counselling and testing centres. Attrition at 12 months on ART was 33.9% and was more likely among infants with WHO Stage 4 [adjusted hazard ratio (AHR)=3.1. 95% CI: 1.8 to 5.2] and severe malnutrition (AHR=1.4, 95% CI: 1.0 to 1.9). Among 599 children eligible for ART at enrolment, cumulative ART initiation incidence was 51.8, 68.6 and 76.1% at one, three, and six months. Children were more likely to start ART if enrolled in 2012 (AsHR=1.8, 95% CI: 1.4 to 2.3) or 2011 (AsHR=1.5, 95% CI: 1.2 to 1.8) compared to

  11. Regenerative endodontics and tissue engineering: what the future holds?

    Science.gov (United States)

    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.

  12. Regenerative medicine: looking backward 10 years further on.

    Science.gov (United States)

    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..

  13. 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....

  14. 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....

  15. New concepts and challenges in the clinical translation of cancer preventive therapies: the role of pharmacodynamic biomarkers.

    Science.gov (United States)

    Brown, Karen; Rufini, Alessandro

    2015-01-01

    Implementation of therapeutic cancer prevention strategies has enormous potential for reducing cancer incidence and related mortality. Trials of drugs including tamoxifen and aspirin have led the way in demonstrating proof-of-principle that prevention of breast and colorectal cancer is feasible. Many other compounds ranging from drugs in widespread use for various indications, including metformin, bisphosphonates, and vitamin D, to dietary agents such as the phytochemicals resveratrol and curcumin, show preventive activity against several cancers in preclinical models. Notwithstanding the wealth of opportunities, major challenges have hindered the development process and only a handful of therapies are currently approved for cancer risk reduction. One of the major obstacles to successful clinical translation of promising preventive agents is a lack of pharmacodynamic biomarkers to provide an early read out of biological activity in humans and for optimising doses to take into large scale randomised clinical trials. A further confounding factor is a lack of consideration of clinical pharmacokinetics in the design of preclinical experiments, meaning results are frequently reported from studies that use irrelevant or unachievable concentrations. This article focuses on recent findings from investigations with dietary-derived agents to illustrate how a thorough understanding of the mechanisms of action, using models that mimic the clinical scenario, together with the development of compound-specific accompanying pharmacodynamic biomarkers could accelerate the developmental pipeline for preventive agents and maximise the chances of success in future clinical trials. Moreover, the concept of a bell-shaped dose-response curve for therapeutic cancer prevention is discussed, along with the need to rethink the traditional 'more is better' approach for dose selection.

  16. Scaffolds in regenerative endodontics: A review

    Science.gov (United States)

    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

  17. Scaffolds in regenerative endodontics: A review

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

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

    Science.gov (United States)

    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.

  20. 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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    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.

  4. Regenerative liver surgeries: the alphabet soup of emerging techniques.

    Science.gov (United States)

    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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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.

  8. 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....

  9. Translation Techniques

    OpenAIRE

    Marcia Pinheiro

    2015-01-01

    In this paper, we discuss three translation techniques: literal, cultural, and artistic. Literal translation is a well-known technique, which means that it is quite easy to find sources on the topic. Cultural and artistic translation may be new terms. Whilst cultural translation focuses on matching contexts, artistic translation focuses on matching reactions. Because literal translation matches only words, it is not hard to find situations in which we should not use this technique.  Because a...

  10. Building Capacity of Occupational Therapy Practitioners to Address the Mental Health Needs of Children and Youth: A Mixed-Methods Study of Knowledge Translation

    Science.gov (United States)

    Demirjian, Louise; LaGuardia, Teri; Thompson-Repas, Karen; Conway, Carol; Michaud, Paula

    2015-01-01

    PURPOSE. We explored the meaning and outcomes of a 6-mo building capacity process designed to promote knowledge translation of a public health approach to mental health among pediatric occupational therapy practitioners participating in a Community of Practice. METHOD. A one-group (N = 117) mixed-methods design using a pretest–posttest survey and qualitative analysis of written reflections was used to explore the meaning and outcomes of the building capacity process. RESULTS. Statistically significant improvements (p occupational therapy’s role in addressing children’s mental health. PMID:26565099

  11. 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.

  12. 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

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.

  17. Regenerative Rehabilitation – a New Future?

    Science.gov (United States)

    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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

    Science.gov (United States)

    Braun, Dominique L; Rauch, Andri; Aouri, Manel; Durisch, Nina; Eberhard, Nadia; Anagnostopoulos, Alexia; Ledergerber, Bruno; Müllhaupt, Beat; Metzner, Karin J; Decosterd, Laurent; Böni, Jürg; Weber, Rainer; Fehr, Jan

    2015-01-01

    adverse events and no significant drug-drug interactions were associated with silibinin. A lead-in with silibinin before triple-therapy was safe and highly effective in difficult-to-treat HIV/HCV coinfected patients, with a pronounced HCV-RNA decline during the lead-in phase, which translates into 63% SVR. An add-on of intravenous silibinin to standard of care HCV treatment is worth further exploration in selected difficult-to-treat patients. ClinicalTrials.gov NCT01816490.

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

    Science.gov (United States)

    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.

  4. 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

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

    Science.gov (United States)

    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

  6. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy; Modelo de radionecrose cutanea induzida em camundongos Nude (Nu/Nu) para desenvolvimento de terapias regenerativas baseadas em substitutos dermo-epidermicos humanos

    Energy Technology Data Exchange (ETDEWEB)

    Mosca, Rodrigo Crespo

    2014-07-01

    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)

  7. Reports from the 2010 Clinical and Translational Cancer Research Think Tank meeting: design strategies for personalized therapy trials.

    Science.gov (United States)

    Berry, Donald A; Herbst, Roy S; Rubin, Eric H

    2012-02-01

    It has long been evident that cancer is a heterogeneous disease, but only relatively recently have we come to realize the extent of this heterogeneity. No single therapy is effective for every patient with tumors having the same histology. A clinical strategy based on a single-therapy approach results in overtreatment for the majority of patients. Biomarkers can be considered as knives that dissect the disease ever more finely. The future of clinical research will be based on learning whether certain therapies are more appropriate than others for biomarker-defined subsets of patients. Therapies will eventually be tailored to narrow biomarker subsets. The ability to determine which therapies are appropriate for which patients requires information from biological science as well as empirical evidence from clinical trials. Neither is easy to achieve. Here we describe some nascent approaches for designing clinical trials that are biomarker-based and adaptive. Our focus is on adaptive trials that address many questions at once. In a way, these clinical experiments are themselves part of a much larger experiment: learning how (or whether it is possible) to design experiments that match patients in small subsets of disease with therapies that are especially effective and possibly even curative for them.

  8. 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.

  9. Translational Creativity

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    A long-established approach to legal translation focuses on terminological equivalence making translators strictly follow the words of source texts. Recent research suggests that there is room for some creativity allowing translators to deviate from the source texts. However, little attention...... is given to genre conventions in source texts and the ways in which they can best be translated. I propose that translators of statutes with an informative function in expert-to-expert communication may be allowed limited translational creativity when translating specific types of genre convention....... This creativity is a result of translators adopting either a source-language or a target-language oriented strategy and is limited by the pragmatic principle of co-operation. Examples of translation options are provided illustrating the different results in target texts. The use of a target-language oriented...

  10. Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia.

    Science.gov (United States)

    Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Paiva, Carlos Eduardo; Barroso, Eliane Marçon; Camargos, Mayara Goulart de; Tsunoda, Audrey Tieko; Longatto-Filho, Adhemar; Paiva, Bianca Sakamoto Ribeiro

    2017-01-01

    To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to the Portuguese language. A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term "pelvic area". The question CD5, "I worry about spreading the infection", was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia. Traduzir e adaptar o instrumento Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD), para a língua portuguesa. Estudo descritivo, transversal, com metodologia de tradução e adaptação cultural de instrumento de avaliação, realizado por meio de diretrizes internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do Brasil

  11. 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...

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

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? Over some 20 years, realization that (1) chronic inflammation is intricately associated with cancer, and (2) the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of “final common pathways” of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This “missing” aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer therapy. This aspect has been somewhat obscured and has been “lost in translation” to date

  13. REGEN: Ancestral Genome Reconstruction for Bacteria

    Directory of Open Access Journals (Sweden)

    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.

  14. Changes in Regenerative Capacity through Lifespan

    Directory of Open Access Journals (Sweden)

    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.

  15. REGEN: Ancestral Genome Reconstruction for Bacteria.

    Science.gov (United States)

    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.

  16. Machine Translation

    Indian Academy of Sciences (India)

    Research Mt System Example: The 'Janus' Translating Phone Project. The Janus ... based on laptops, and simultaneous translation of two speakers in a dialogue. For more ..... The current focus in MT research is on using machine learning.

  17. Characterization and comparison of "Standard" and "Young" tumor infiltrating lymphocytes for adoptive cell therapy at a Danish Translational Research Institution

    DEFF Research Database (Denmark)

    Donia, Marco; Junker, Niels; Ellebaek, Eva

    2012-01-01

    Adoptive cell therapy (ACT) with ex vivo expanded tumor infiltrating lymphocytes (TILs) in combination with IL-2 is an effective treatment for patients with metastatic melanoma. Modified protocols of cell expansion may allow treatment of most enrolled patients and improve the efficacy of adoptively...

  18. A regenerative elastocaloric heat pump

    DEFF Research Database (Denmark)

    Engelbrecht, Kurt; Eriksen, Dan; Dallolio, Stefano

    2016-01-01

    A large fraction of global energy use is for refrigeration and air-conditioning, which could be decarbonized if efficient renewable energy technologies could be found. Vapour-compression technology remains the most widely used system to move heat up the temperature scale after more than 100 years...... a regenerative elastocaloric heat pump that exhibits a temperature span of 15.3 K on the water side with a corresponding specific heating power up to 800 W kg−1 and maximum COP (coefficient-of-performance) values of up to 7. The efficiency and specific heating power of this device exceeds those of other devices...... based on caloric effects. These results open up the possibility of using the elastocaloric effect in various cooling and heat-pumping applications....

  19. Regenerative Medicine: Solution in Sight.

    Science.gov (United States)

    Wang, Qingjie; Stern, Jeffrey H; Temple, Sally

    2016-01-01

    The retina, like other central nervous system tissues, has poor regenerative properties in humans. Therefore, diseases that cause retinal cell loss, such as Age-related macular degeneration (AMD), retinitis pigmentosa (RP), Leber congenital amaurosis, Usher syndrome, glaucoma, and diabetic retinopathy, typically result in permanent visual impairment. Stem cell technologies have revolutionized our ability to produce neural cells in abundant supply. Much stem cell research effort is focused on producing the required cell types for cell replacement, or to generate disease-in-a-dish models to elucidate novel disease mechanisms for therapeutic development. Here we review the recent advances in stem cell studies relevant to producing RPE and retinal cells, and highlight future directions.

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

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret

    2008-01-01

    , nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......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...

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

    Science.gov (United States)

    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.

  2. 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.

  3. Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations.

    Science.gov (United States)

    Nagel-Wolfrum, Kerstin; Möller, Fabian; Penner, Inessa; Wolfrum, Uwe

    2014-09-01

    The eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment strategy based on the usage of translational read-through inducing drugs (TRIDs) such as PTC124, aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame nonsense mutations. This strategy has emerged as an option for up to 30-50% of all cases of recessive hereditary retinal dystrophies. In-frame nonsense mutations are single-nucleotide alterations within the gene coding sequence resulting in a premature stop codon. Consequently, translation of such mutated genes leads to the synthesis of truncated proteins, which are unable to fulfill their physiologic functions. In this context, application of TRIDs facilitates the recoding of the premature termination codon into a sense codon, thus restoring syntheses of full-length proteins. So far, clinical trials for non-ocular diseases have been initiated for diverse TRIDs. Although the clinical outcome is not analyzed in detail, an excellent safety profile, namely for PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained read-through efficacies of nonsense mutations causing retinal degeneration, as manifested in the human Usher syndrome. In addition, a strong retinal biocompatibility for PTC124 and designer aminoglycosides has been demonstrated. In conclusion, recent progress emphasizes the

  4. 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.

  5. Machine translation

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, M

    1982-04-01

    Each language has its own structure. In translating one language into another one, language attributes and grammatical interpretation must be defined in an unambiguous form. In order to parse a sentence, it is necessary to recognize its structure. A so-called context-free grammar can help in this respect for machine translation and machine-aided translation. Problems to be solved in studying machine translation are taken up in the paper, which discusses subjects for semantics and for syntactic analysis and translation software. 14 references.

  6. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

    OpenAIRE

    de Lange, Elizabeth CM

    2013-01-01

    Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

  7. Th17 Pathway As a Target for Multipotent Stromal Cell Therapy in Dogs: Implications for Translational Research.

    Science.gov (United States)

    Kol, A; Walker, N J; Nordstrom, M; Borjesson, D L

    2016-01-01

    Detrimental Th17 driven inflammatory and autoimmune disease such as Crohn's disease, graft versus host disease and multiple sclerosis remain a significant cause of morbidity and mortality worldwide. Multipotent stromal/stem cell (MSC) inhibit Th17 polarization and activation in vitro and in rodent models. As such, MSC based therapeutic approaches are being investigated as novel therapeutic approaches to treat Th17 driven diseases in humans. The significance of naturally occurring diseases in dogs is increasingly recognized as a realistic platform to conduct pre-clinical testing of novel therapeutics. Full characterization of Th17 cells in dogs has not been completed. We have developed and validated a flow-cytometric method to detect Th17 cells in canine blood. We further demonstrate that Th17 and other IL17 producing cells are present in tissues of dogs with naturally occurring chronic inflammatory diseases. Finally, we have determined the kinetics of a canine specific Th17 polarization in vitro and demonstrate that canine MSC inhibit Th17 polarization in vitro, in a PGE2 independent mechanism. Our findings provide fundamental research tools and suggest that naturally occurring diseases in dogs, such as inflammatory bowel disease, may be harnessed to translate novel MSC based therapeutic strategies that target the Th17 pathway.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. Translating India

    CERN Document Server

    Kothari, Rita

    2014-01-01

    The cultural universe of urban, English-speaking middle class in India shows signs of growing inclusiveness as far as English is concerned. This phenomenon manifests itself in increasing forms of bilingualism (combination of English and one Indian language) in everyday forms of speech - advertisement jingles, bilingual movies, signboards, and of course conversations. It is also evident in the startling prominence of Indian Writing in English and somewhat less visibly, but steadily rising, activity of English translation from Indian languages. Since the eighties this has led to a frenetic activity around English translation in India's academic and literary circles. Kothari makes this very current phenomenon her chief concern in Translating India.   The study covers aspects such as the production, reception and marketability of English translation. Through an unusually multi-disciplinary approach, this study situates English translation in India amidst local and global debates on translation, representation an...

  11. Translating Inclusion

    DEFF Research Database (Denmark)

    Fallov, Mia Arp; Birk, Rasmus

    2018-01-01

    The purpose of this paper is to explore how practices of translation shape particular paths of inclusion for people living in marginalized residential areas in Denmark. Inclusion, we argue, is not an end-state, but rather something which must be constantly performed. Active citizenship, today......, is not merely a question of participation, but of learning to become active in all spheres of life. The paper draws on empirical examples from a multi-sited field work in 6 different sites of local community work in Denmark, to demonstrate how different dimensions of translation are involved in shaping active...... citizenship. We propose the following different dimensions of translation: translating authority, translating language, translating social problems. The paper takes its theoretical point of departure from assemblage urbanism, arguing that cities are heterogeneous assemblages of socio-material interactions...

  12. 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...

  13. A regenerative elastocaloric heat pump

    Science.gov (United States)

    Tušek, Jaka; Engelbrecht, Kurt; Eriksen, Dan; Dall'Olio, Stefano; Tušek, Janez; Pryds, Nini

    2016-10-01

    A large fraction of global energy use is for refrigeration and air-conditioning, which could be decarbonized if efficient renewable energy technologies could be found. Vapour-compression technology remains the most widely used system to move heat up the temperature scale after more than 100 years; however, caloric-based technologies (those using the magnetocaloric, electrocaloric, barocaloric or elastocaloric effect) have recently shown a significant potential as alternatives to replace this technology due to high efficiency and the use of green solid-state refrigerants. Here, we report a regenerative elastocaloric heat pump that exhibits a temperature span of 15.3 K on the water side with a corresponding specific heating power up to 800 W kg-1 and maximum COP (coefficient-of-performance) values of up to 7. The efficiency and specific heating power of this device exceeds those of other devices based on caloric effects. These results open up the possibility of using the elastocaloric effect in various cooling and heat-pumping applications.

  14. Staged regenerative sorption heat pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    1995-01-01

    A regenerative adsorbent heat pump process and system for cooling and heating a space. A sorbent is confined in a plurality of compressors of which at least four are first stage and at least four are second stage. The first stage operates over a first pressure region and the second stage over a second pressure region which is higher than the first. Sorbate from the first stage enters the second stage. The sorbate loop includes a condenser, expansion valve, evaporator and the compressors. A single sorbate loop can be employed for single-temperature-control such as air conditioning and heating. Two sorbate loops can be used for two-temperature-control as in a refrigerator and freezer. The evaporator temperatures control the freezer and refrigerator temperatures. Alternatively the refrigerator temperature can be cooled by the freezer with one sorbate loop. A heat transfer fluid is circulated in a closed loop which includes a radiator and the compressors. Low temperature heat is exhausted by the radiator. High temperature heat is added to the heat transfer fluid entering the compressors which are desorbing vapor. Heat is transferred from compressors which are sorbing vapor to the heat transfer fluid, and from the heat transfer fluid to the compressors which are desorbing vapor. Each compressor is subjected to the following phases, heating to its highest temperature, cooling down from its highest temperature, cooling to its lowest temperature, and warming up from its lowest temperature. The phases are repeated to complete a cycle and regenerate heat.

  15. 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

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

    Science.gov (United States)

    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.

  17. Compositional translation

    NARCIS (Netherlands)

    Appelo, Lisette; Janssen, Theo; Jong, de F.M.G.; Landsbergen, S.P.J.

    1994-01-01

    This book provides an in-depth review of machine translation by discussing in detail a particular method, called compositional translation, and a particular system, Rosetta, which is based on this method. The Rosetta project is a unique combination of fundamental research and large-scale

  18. Honey: an effective regenerative medicine product in wound management.

    Science.gov (United States)

    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.

  19. The Importance of “Orff-Schulwerk” for Musical Social-Integrative Pedagogy and Music Therapy (English translation: Gloria Litwin

    Directory of Open Access Journals (Sweden)

    Karin Schumacher

    2013-12-01

    Full Text Available Which features of Carl Orff and Gunild Keetman’s ideas are relevant for work in the community and therapy? A child who is mentally or physically handicapped, emotionally or sensorially disabled or on the autistic spectrum, is never just only that. The characteristics of a person that are not expressed in these terms, however, are precisely the ones that make musical communication and thus a connection with so-called ‘normal’ people possible. A historical review will demonstrate the sources from which the adaptation of the Schulwerk for work with handicapped and disturbed children and young people was made possible and meaningful. A brief section will define the fields of “Music Education”, “Music in Special Needs and Community” and “Music Therapy” in order to distinguish them and highlight the contents they have in common. The author uses quotes by Carl Orff in order to document the basis of her ideas for therapeutic work and describes how pedagogues and therapists, from the early sixties until today, have developed them for and together with different groups with special needs: - The multi-sensorial approach through speech, free and bound rhythm, movement, singing and playing instruments provides possibilities for spontaneous creative play in a social context, even if one important sensorial area is severely damaged. - Every member of an integrative music and movement group is participating actively in a creative process. - The instrumentarium allows participants to play together in a spontaneous way. - Relationships developed through musical expression and play as an encounter between two people forms the basis for emotional development. - Musical reception and expression is independent of intellectual capacity, age and previous musical experience.

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

    Science.gov (United States)

    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.

  1. 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

  2. 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.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Precision translator

    Science.gov (United States)

    Reedy, Robert P.; Crawford, Daniel W.

    1984-01-01

    A precision translator for focusing a beam of light on the end of a glass fiber which includes two turning fork-like members rigidly connected to each other. These members have two prongs each with its separation adjusted by a screw, thereby adjusting the orthogonal positioning of a glass fiber attached to one of the members. This translator is made of simple parts with capability to keep adjustment even in condition of rough handling.

  6. 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.

  7. Stem Cells in Regenerative Medicine

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva; Forostyak, Serhiy

    2013-01-01

    Roč. 22, č. 2 (2013), s. 87-92 ISSN 0898-5901 R&D Projects: GA ČR(CZ) GAP304/11/0189; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : cell therapy * stem cells * clinical study Subject RIV: FH - Neurology

  8. Combined hydraulic and regenerative braking system

    Science.gov (United States)

    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.

  9. Clinical considerations for regenerative endodontic procedures.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. 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.

  12. 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.

  13. 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…

  14. 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...

  15. 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.

  16. 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 ...

  17. 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

  18. 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 ...

  19. 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.

  20. 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.

  1. 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

  2. Giant hepatic regenerative nodules in Alagille syndrome

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. Translation Competence

    DEFF Research Database (Denmark)

    Vandepitte, Sonia; Mousten, Birthe; Maylath, Bruce

    2014-01-01

    After Kiraly (2000) introduced the collaborative form of translation in classrooms, Pavlovic (2007), Kenny (2008), and Huertas Barros (2011) provided empirical evidence that testifies to the impact of collaborative learning. This chapter sets out to describe the collaborative forms of learning at...

  4. Translating Harbourscapes

    DEFF Research Database (Denmark)

    Diedrich, Lisa Babette

    -specific design are proposed for all actors involved in harbour transformation. The study ends with an invitation to further investigate translation as a powerful metaphor for the way existing qualities of a site can be transformed, rather than erased or rewritten, and to explore how this metaphor can foster new...

  5. Word translation entropy in translation

    DEFF Research Database (Denmark)

    Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

    2016-01-01

    This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied....... In particular, the current study investigates the effect of these variables on early and late eye movement measures. Early eye movement measures are indicative of processes that are more automatic while late measures are more indicative of conscious processing. Most studies that found evidence of target...... language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...

  6. 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

  7. 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.

  8. 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.

  9. Translational genomics

    Directory of Open Access Journals (Sweden)

    Martin Kussmann

    2014-09-01

    Full Text Available The term “Translational Genomics” reflects both title and mission of this new journal. “Translational” has traditionally been understood as “applied research” or “development”, different from or even opposed to “basic research”. Recent scientific and societal developments have triggered a re-assessment of the connotation that “translational” and “basic” are either/or activities: translational research nowadays aims at feeding the best science into applications and solutions for human society. We therefore argue here basic science to be challenged and leveraged for its relevance to human health and societal benefits. This more recent approach and attitude are catalyzed by four trends or developments: evidence-based solutions; large-scale, high dimensional data; consumer/patient empowerment; and systems-level understanding.

  10. Beyond Translation

    DEFF Research Database (Denmark)

    Olwig, Mette Fog

    2013-01-01

    This article contributes to the growing scholarship on local development practitioners by re-examining conceptualizations of practitioners as ‘brokers’ strategically translating between ‘travelling’ (development institution) rationalities and ‘placed’ (recipient area) rationalities in relation...... and practice spurred by new challenges deriving from climate change anxiety, the study shows how local practitioners often make local activities fit into travelling development rationalities as a matter of habit, rather than as a conscious strategy. They may therefore cease to ‘translate’ between different...... rationalities. This is shown to have important implications for theory, research and practice concerning disaster risk reduction and climate change adaptation in which such translation is often expected....

  11. Revising Translations

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten Wølch; Schjoldager, Anne

    2011-01-01

    The paper explains the theoretical background and findings of an empirical study of revision policies, using Denmark as a case in point. After an overview of important definitions, types and parameters, the paper explains the methods and data gathered from a questionnaire survey and an interview...... survey. Results clearly show that most translation companies regard both unilingual and comparative revisions as essential components of professional quality assurance. Data indicate that revision is rarely fully comparative, as the preferred procedure seems to be a unilingual revision followed by a more...... or less comparative rereading. Though questionnaire data seem to indicate that translation companies use linguistic correctness and presentation as the only revision parameters, interview data reveal that textual and communicative aspects are also considered. Generally speaking, revision is not carried...

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

    Science.gov (United States)

    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.

  13. 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.

  14. [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.

  15. 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.

  16. 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.

  17. 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

  18. 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

    2016-01-01

    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

  19. 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

  20. Optimization of an irreversible Stirling regenerative cycle

    International Nuclear Information System (INIS)

    Aragón-González, G; Cano-Bianco, M; León-Galicia, A; Rivera-Camacho, J M

    2015-01-01

    In this work a Stirling regenerative cycle with some irreversibilities is analyzed. The analyzed irreversibilities are located at the heat exchangers. They receive a finite amount of heat and heat leakage occurs between both reservoirs. Using this model, power and the efficiency at maximum power are obtained. Some optimal design parameters for the exchanger heat areas and thermal conductances are presented. The relation between the power, efficiency and the results obtained are shown graphically

  1. 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...

  2. Induced Pluripotent Stem Cells for Regenerative Medicine

    OpenAIRE

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

    2014-01-01

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies...

  3. 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.

  4. A solar regenerative thermoelectrochemical converter (RTEC)

    Energy Technology Data Exchange (ETDEWEB)

    Townsend, C.W.; McHardy, J. (Hughes Aircraft Co., El Segundo, CA (United States))

    1992-02-01

    This is an executive summary of a final subcontract report that describes the successful completion of a closed-loop demonstration of a regenerative thermoelectromechanical device using solar heat input for the production of electricity. The full report, which contains a detailed description of the two-year effort, is currently subject to a government secrecy order which precludes public release of the information. Copies of the full report will be made available for general release whenever the secrecy order is lifted.

  5. 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.

  6. 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.

  7. Regenerative endodontics--Creating new horizons.

    Science.gov (United States)

    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.

  8. 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.

  9. 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).

  10. 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.

  11. Translating democracy

    DEFF Research Database (Denmark)

    Doerr, Nicole

    2012-01-01

    Linguistic barriers may pose problems for politicians trying to communicate delicate decisions to a European-wide public, as well as for citizens wishing to protest at the European level. In this article I present a counter-intuitive position on the language question, one that explores how...... Forum (ESF). I compare deliberative practices in the multilingual ESF preparatory meetings with those in monolingual national Social Forum meetings in three Western European countries. My comparison shows that multilingualism does not reduce the inclusivity of democratic deliberation as compared...... in institutionalized habits and norms of deliberation. Addressing democratic theorists, my findings suggest that translation could be a way to think about difference not as a hindrance but as a resource for democracy in linguistically heterogeneous societies and public spaces, without presupposing a shared language...

  12. Translator's preface.

    Science.gov (United States)

    Lamiell, James T

    2013-08-01

    Presents a preface from James T. Lamiell, who translates Wilhelm Wundt's Psychology's Struggle for Existence (Die Psychologie im Kampf ums Dasein), in which Wundt advised against the impending divorce of psychology from philosophy, into English. Lamiell comments that more than a decade into the 21st century, it appears that very few psychologists have any interest at all in work at the interface of psychology and philosophy. He notes that one clear indication of this is that the Society for Theoretical and Philosophical Psychology, which is Division 24 of the American Psychological Association (APA), remains one of the smallest of the APA's nearly 60 divisions. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  13. 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...

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 3D Biomaterial Microarrays for Regenerative Medicine

    DEFF Research Database (Denmark)

    Gaharwar, Akhilesh K.; Arpanaei, Ayyoob; Andresen, Thomas Lars

    2015-01-01

    Three dimensional (3D) biomaterial microarrays hold enormous promise for regenerative medicine because of their ability to accelerate the design and fabrication of biomimetic materials. Such tissue-like biomaterials can provide an appropriate microenvironment for stimulating and controlling stem...... for tissue engineering and drug screening applications....... cell differentiation into tissue-specifi c lineages. The use of 3D biomaterial microarrays can, if optimized correctly, result in a more than 1000-fold reduction in biomaterials and cells consumption when engineering optimal materials combinations, which makes these miniaturized systems very attractive...

  19. Bioprinting is changing regenerative medicine forever.

    Science.gov (United States)

    Collins, Scott Forrest

    2014-12-01

    3D printing, or solid freeform fabrication, applied to regenerative medicine brings technologies from several industries together to help solve unique challenges in both basic science and tissue engineering. By more finely organizing cells and supporting structures precisely in 3D space, we will gain critical knowledge of cell-cell communications and cell-environment interactions. As we increase the scale, we will move toward complex tissue and organ structures where several cell phenotypes will functionally and structurally interact, thus recapitulating the form and function of native tissues and organs.

  20. Feasibility investigation of allogeneic endometrial regenerative cells

    Directory of Open Access Journals (Sweden)

    Reid Michael

    2009-02-01

    Full Text Available Abstract Endometrial Regenerative Cells (ERC are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type.

  1. Phosphorous-Containing Polymers for Regenerative Medicine

    Science.gov (United States)

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

    2014-01-01

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

  2. Translation and validation of the Persian version of the functional assessment of chronic illness therapy-Spiritual well-being scale (FACIT-Sp) among Muslim Iranians in treatment for cancer.

    Science.gov (United States)

    Jafari, Najmeh; Zamani, Ahmadreza; Lazenby, Mark; Farajzadegan, Ziba; Emami, Hamid; Loghmani, Amir

    2013-02-01

    The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) scale is a valid and reliable instrument to provide an inclusive measure of spirituality in research and clinical practice. The aim of this study was to translate and investigate the reliability and validity of the Persian version of the FACIT-Sp. The 12 item spiritual well-being subscale of the FACIT-Sp Version 4 was translated into the Persian language, Farsi, using the FACIT translation methodology. The questionnaire was administered to a diverse sample of 153 patients in treatment for cancer. Internal consistency was assessed by Cronbach's α coefficient, confirmatory factor analysis (CFA) was applied to assess construct validity, and regression analysis was used to assess the predictor role of the FACIT-Sp in health-related quality of life (HRQOL). Cronbach's α reliability coefficient for the FACIT-Sp subscales ranged from 0.72 to 0.90. The CFA generally replicated the original conceptualization of the three subscales of the FACIT-Sp12 (Peace, Meaning, and Faith). All three subscales significant predicted HRQOL. The Persian version of the FACIT-Sp scale is a reliable and valid tool for the clinical assessment of, and research into, the spiritual well-being of Muslim Iranian and Farsi-speaking patients in other regions of the world who are in treatment for cancer.

  3. Imperative Role of Dental Pulp Stem Cells in Regenerative Therapies

    African Journals Online (AJOL)

    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, ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Tissue engineering and regenerative medicine: manufacturing challenges.

    Science.gov (United States)

    Williams, D J; Sebastine, I M

    2005-12-01

    Tissue engineering and regenerative medicine are interdisciplinary fields that apply principles of engineering and life sciences to develop biological substitutes, typically composed of biological and synthetic components, that restore, maintain or improve tissue function. Many tissue engineering technologies are still at a laboratory or pre-commercial scale. The short review paper describes the most significant manufacturing and bio-process challenges inherent in the commercialisation and exploitation of the exciting results emerging from the biological and clinical laboratories exploring tissue engineering and regenerative medicine. A three-generation road map of the industry has been used to structure a view of these challenges and to define where the manufacturing community can contribute to the commercial success of the products from these emerging fields. The first-generation industry is characterised by its demonstrated clinical applications and products in the marketplace, the second is characterised by emerging clinical applications, and the third generation is characterised by aspirational clinical applications. The paper focuses on the cost reduction requirement of the first generation of the industry to allow more market penetration and consequent patient impact. It indicates the technological requirements, for instance the creation of three-dimensional tissue structures, and value chain issues in the second generation of the industry. The third-generation industry challenges lie in fundamental biological and clinical science. The paper sets out a road map of these generations to identify areas for research.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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,

  14. 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.

  15. 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.

  16. 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.

  17. Solar Airplanes and Regenerative Fuel Cells

    Science.gov (United States)

    Bents, David J.

    2007-01-01

    A solar electric aircraft with the potential to "fly forever" has captured NASA's interest, and the concept for such an aircraft was pursued under Aeronautics Environmental Research Aircraft and Sensor Technology (ERAST) project. Feasibility of this aircraft happens to depend on the successful development of solar power technologies critical to NASA's Exploration Initiatives; hence, there was widespread interest throughout NASA to bring these technologies to a flight demonstration. The most critical is an energy storage system to sustain mission power during night periods. For the solar airplane, whose flight capability is already limited by the diffuse nature of solar flux and subject to latitude and time of year constraints, the feasibility of long endurance flight depends on a storage density figure of merit better than 400-600 watt-hr per kilogram. This figure of merit is beyond the capability of present day storage technologies (other than nuclear) but may be achievable in the hydrogen-oxygen regenerative fuel cell (RFC). This potential has led NASA to undertake the practical development of a hydrogen-oxygen regenerative fuel cell, initially as solar energy storage for a high altitude UAV science platform but eventually to serve as the primary power source for NASAs lunar base and other planet surface installations. Potentially the highest storage capacity and lowest weight of any non-nuclear device, a flight-weight RFC aboard a solar-electric aircraft that is flown continuously through several successive day-night cycles will provide the most convincing demonstration that this technology's widespread potential has been realized. In 1998 NASA began development of a closed cycle hydrogen oxygen PEM RFC under the Aeronautics Environmental Research Aircraft and Sensor Technology (ERAST) project and continued its development, originally for a solar electric airplane flight, through FY2005 under the Low Emissions Alternative Power (LEAP) project. Construction of

  18. 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.

  19. THE TRANSLATION, VALIDATION AND CULTURAL ADAPTATION OF FUNCTIONAL ASSESSMENT OF CHRONIC ILLNESS THERAPY - SPIRITUAL WELL-BEING 12 (FACIT-SP12) SCALE IN GREEK LANGUAGE.

    Science.gov (United States)

    Fradelos, Evangelos C; Tzavella, Foteini; Koukia, Evmorfia; Tsaras, Konstantinos; Papathanasiou, Ioanna V; Aroni, Adamantia; Alikari, Victoria; Ralli, Maria; Bredle, Jason; Zyga, Sofia

    2016-06-01

    According to World Health Organization (WHO), spirituality is an important domain of quality of life especially in terminal, life threatens chronic diseases. For many people spirituality and religion are not just very important dimensions of their existence, but also a source of support that contributes to wellbeing and coping with everyday difficulties of life. Aim of the study was the translation of the Facit Spiritual Well Being Scale (Facit-Sp12) in Greek language and the validation of the scale for the Greek population. The Facit-Sp12 questionnaire is an anonymous self-administered questionnaire that contains twelve, four point Likert scale, closed questions (0=Not at all, 1=A little bit, 2=Some-what, 3=Quite a bit, 4=Very Much). The questionnaire was translated into Greek language and then back translated in the English in order to be checked for any inconsistencies. The sample of the study was 183 chronic kidney disease patients, undergoing hemodialysis. Exploratory factor analysis, with principal components analysis with Varimax rotation was performed for checking the construct validity of the questionnaire. The test-retest reliability and the internal consistency were also examined. Statistical analysis performed by the use of SPSS 21.0. Statistical significance level was set at p=0.05. The final Greek version of the questionnaire includes all of the twelve questions. The mean age of the participants was 61.81±13.9. Three factors were exported from the statistical analysis. The Cronbach-α coefficient was 0.77 for the total questionnaire and for each subscale was 0.70 for "meaning", 0.73 for "peace" and 0.87 for "faith". Between the three subscales "meaning" had the highest score (mean 12.49, SD=2.865). The Facit Spiritual Wellbeing Scale-Facit-Sp12, is a valuable and reliable questionnaire of three dimensions that can be used for assessing spirituality and spiritual wellbeing in Greek population.

  20. A regenerative approach towards mucosal fenestration closure

    Science.gov (United States)

    Gandi, Padma; Anumala, Naveen; Reddy, Amarender; Viswa Chandra, Rampalli

    2013-01-01

    Mucosal fenestration is an opening or an interstice through the oral mucosa. A lesion which occurs with greater frequency than generally realised, its occurrence is attributed to a myriad of causes. Mucogingival procedures including connective tissue grafts, free gingival grafts and lateral pedicle grafts are generally considered to be the treatment of choice in the closure of a mucosal fenestration. More often, these procedures are performed in conjunction with other procedures such as periradicular surgery and with bone grafts. However, the concomitant use of gingival grafts and bone grafts in mucosal fenestrations secondary to infections in sites exhibiting severe bone loss is highly debatable. In this article, we report two cases of mucosal fenestrations secondary to trauma and their management by regenerative periodontal surgery with the placement of guided tissue regeneration membrane and bone graft. The final outcome was a complete closure of the fenestration in both the cases. PMID:23749826

  1. Engineering cell fitness: lessons for regenerative medicine.

    Science.gov (United States)

    Shakiba, Nika; Zandstra, Peter W

    2017-10-01

    Cell competition results in the loss of weaker cells and the dominance of stronger cells. So-called 'loser' cells are either removed by active elimination or by limiting their access to survival factors. Recently, competition has been shown to serve as a surveillance mechanism against emerging aberrant cells in both the developing and adult organism, contributing to overall organism fitness and survival. Here, we explore the origins and implications of cell competition in development, tissue homeostasis, and in vitro culture. We also provide a forward look on the use of cell competition to interpret multicellular dynamics while offering a perspective on harnessing competition to engineer cells with optimized and controllable fitness characteristics for regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. A regenerative zinc-air fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Smedley, Stuart I. [Electrochemical Technology Development Ltd., Lower Hutt (New Zealand); Zhang, X. Gregory [Teck Cominco Metals Ltd., 2380 Speakman Drive, Mississauga, Ontario (Canada)

    2007-03-20

    The zinc regenerative fuel cell (ZRFC) developed by the former Metallic Power Inc. over the period from 1998 to 2004 is described. The component technologies and engineering solutions for various technical issues are discussed in relation to their functionality in the system. The system was designed to serve as a source of backup emergency power for remote or difficult to access cell phone towers during periods when the main power was interrupted. It contained a 12 cell stack providing 1.8 kW, a separate fuel tank containing zinc pellet fuel and electrolyte, and a zinc electrolyzer to regenerate the zinc pellets during standby periods. Offsite commissioning and testing of the system was successfully performed. The intellectual property of the ZRFC technology is now owned by Teck Cominco Metals Ltd. (author)

  3. Regenerative immunology: the immunological reaction to biomaterials.

    Science.gov (United States)

    Cravedi, Paolo; Farouk, Samira; Angeletti, Andrea; Edgar, Lauren; Tamburrini, Riccardo; Duisit, Jerome; Perin, Laura; Orlando, Giuseppe

    2017-12-01

    Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression-free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials-both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes. This review will succinctly discuss progress in the understanding of immunological characteristics and behavior of different scaffolds currently under development, with emphasis on the extracellular matrix scaffolds obtained decellularized animal or human organs which seem to provide the ideal template for bioengineering purposes. © 2017 Steunstichting ESOT.

  4. ADRES : autonomous decentralized regenerative energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, G.; Einfalt, A.; Leitinger, C.; Tiefgraber, D. [Vienna Univ. of Technology (Austria)

    2007-07-01

    The autonomous decentralized regenerative energy systems (ADRES) research project demonstrates that decentralized network independent microgrids are the target power systems of the future. This paper presented a typical structure of a microgrid, demonstrating that all types of generation available can be integrated, from wind and small hydro to photovoltaic, fuel cell, biomass or biogas operated stirling motors and micro turbines. In grid connected operation the balancing energy and reactive power for voltage control will come from the public grid. If there is no interconnection to a superior grid, it will form an autonomous micro grid. In order to reduce peak power demand and base energy, autonomous microgrid technology requires highly efficient appliances. Otherwise large collector design, high storage and balancing generation capacities would be necessary, which would increase costs. End-use energy efficiency was discussed with reference to demand side management (DSM) strategies that match energy demand with actual supply in order to minimize the storage size needed. This paper also discussed network controls that comprise active and reactive power. Decentralized robust algorithms were investigated with reference to black-start ability and congestion management features. It was concluded that the trend to develop small decentralized grids in parallel to existing large systems will improve security of supply and reduce greenhouse gas emissions. Decentralized grids will also increase energy efficiency because regenerative energy will be used where it is collected in the form of electricity and heat, thus avoiding transport and the extension of transmission lines. Decentralized energy technology is now becoming more economic by efficient and economic mass production of components. Although decentralized energy technology requires energy automation, computer intelligence is becoming increasingly cost efficient. 2 refs., 4 figs.

  5. The TMI Regenerative Solid Oxide Fuel Cell

    Science.gov (United States)

    Cable, Thomas L.; Ruhl, Robert C.; Petrik, Michael

    1996-01-01

    Energy storage and production in space requires rugged, reliable hardware which minimizes weight, volume, and maintenance while maximizing power output and usable energy storage. Systems generally consist of photovoltaic solar arrays which operate (during sunlight cycles) to provide system power and regenerate fuel (hydrogen) via water electrolysis and (during dark cycles) fuel cells convert hydrogen into electricity. Common configurations use two separate systems (fuel cell and electrolyzer) in conjunction with photovoltaic cells. Reliability, power to weight and power to volume ratios could be greatly improved if both power production (fuel cells) and power storage (electrolysis) functions can be integrated into a single unit. The solid oxide fuel cell (SOFC) based design integrates fuel cell and electrolyzer functions and potentially simplifies system requirements. The integrated fuel cell/electrolyzer design also utilizes innovative gas storage concepts and operates like a rechargeable 'hydrogen-oxygen battery'. Preliminary research has been completed on improved H2/H20 electrode (SOFC anode/electrolyzer cathode) materials for regenerative fuel cells. Tests have shown improved cell performance in both fuel and electrolysis modes in reversible fuel cell tests. Regenerative fuel cell efficiencies, ratio of power out (fuel cell mode) to power in (electrolyzer mode), improved from 50 percent using conventional electrode materials to over 80 percent. The new materials will allow a single SOFC system to operate as both the electolyzer and fuel cell. Preliminary system designs have also been developed to show the technical feasibility of using the design for space applications requiring high energy storage efficiencies and high specific energy. Small space systems also have potential for dual-use, terrestrial applications.

  6. Heat cascading regenerative sorption heat pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    1995-01-01

    A simple heat cascading regenerative sorption heat pump process with rejected or waste heat from a higher temperature chemisorption circuit (HTCC) powering a lower temperature physisorption circuit (LTPC) which provides a 30% total improvement over simple regenerative physisorption compression heat pumps when ammonia is both the chemisorbate and physisorbate, and a total improvement of 50% or more for LTPC having two pressure stages. The HTCC contains ammonia and a chemisorbent therefor contained in a plurality of canisters, a condenser-evaporator-radiator system, and a heater, operatively connected together. The LTPC contains ammonia and a physisorbent therefor contained in a plurality of compressors, a condenser-evaporator-radiator system, operatively connected together. A closed heat transfer circuit (CHTC) is provided which contains a flowing heat transfer liquid (FHTL) in thermal communication with each canister and each compressor for cascading heat from the HTCC to the LTPC. Heat is regenerated within the LTPC by transferring heat from one compressor to another. In one embodiment the regeneration is performed by another CHTC containing another FHTL in thermal communication with each compressor. In another embodiment the HTCC powers a lower temperature ammonia water absorption circuit (LTAWAC) which contains a generator-absorber system containing the absorbent, and a condenser-evaporator-radiator system, operatively connected together. The absorbent is water or an absorbent aqueous solution. A CHTC is provided which contains a FHTL in thermal communication with the generator for cascading heat from the HTCC to the LTAWAC. Heat is regenerated within the LTAWAC by transferring heat from the generator to the absorber. The chemical composition of the chemisorbent is different than the chemical composition of the physisorbent, and the absorbent. The chemical composition of the FHTL is different than the chemisorbent, the physisorbent, the absorbent, and ammonia.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Mapping Translation Technology Research in Translation Studies

    DEFF Research Database (Denmark)

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

    2017-01-01

    /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...... 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...... technology research as a subdiscipline of TS, and we define and discuss some basic concepts and models of the field that we use in the rest of the paper. Based on a small-scale study of papers published in TS journals between 2006 and 2016, Section 3 attempts to map relevant developments of translation...

  17. 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.

  18. 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.

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

    Science.gov (United States)

    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. New Regenerative Cycle for Vapor Compression Refrigeration

    Energy Technology Data Exchange (ETDEWEB)

    Mark J. Bergander

    2005-08-29

    The main objective of this project is to confirm on a well-instrumented prototype the theoretically derived claims of higher efficiency and coefficient of performance for geothermal heat pumps based on a new regenerative thermodynamic cycle as comparing to existing technology. In order to demonstrate the improved performance of the prototype, it will be compared to published parameters of commercially available geothermal heat pumps manufactured by US and foreign companies. Other objectives are to optimize the design parameters and to determine the economic viability of the new technology. Background (as stated in the proposal): The proposed technology closely relates to EERE mission by improving energy efficiency, bringing clean, reliable and affordable heating and cooling to the residential and commercial buildings and reducing greenhouse gases emission. It can provide the same amount of heating and cooling with considerably less use of electrical energy and consequently has a potential of reducing our nations dependence on foreign oil. The theoretical basis for the proposed thermodynamic cycle was previously developed and was originally called a dynamic equilibrium method. This theory considers the dynamic equations of state of the working fluid and proposes the methods for modification of T-S trajectories of adiabatic transformation by changing dynamic properties of gas, such as flow rate, speed and acceleration. The substance of this proposal is a thermodynamic cycle characterized by the regenerative use of the potential energy of two-phase flow expansion, which in traditional systems is lost in expansion valves. The essential new features of the process are: (1) The application of two-step throttling of the working fluid and two-step compression of its vapor phase. (2) Use of a compressor as the initial step compression and a jet device as a second step, where throttling and compression are combined. (3) Controlled ratio of a working fluid at the first and

  6. On Various Negative Translations

    Directory of Open Access Journals (Sweden)

    Gilda Ferreira

    2011-01-01

    Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.

  7. Gender issues in translation

    OpenAIRE

    ERGASHEVA G.I.

    2015-01-01

    The following research is done regarding gender in translation dealing specifically with the issue of the translators’ gender identity and its effect on their translations, as well as on how gender itself is translated and produced. We will try to clarify what gender is, how gender manifests itself in the system of language, and what problems translators encounter when translating or producing gender-related materials

  8. Cultural Context and Translation

    Institute of Scientific and Technical Information of China (English)

    张敏

    2009-01-01

    cultural context plays an important role in translation. Because translation is a cross-culture activity, the culture context that influ-ences translating is consisted of both the culture contexts of source language and target language. This article firstly analyzes the concept of context and cultural context, then according to the procedure of translating classifies cultural context into two stages and talks about how they respectively influence translating.

  9. 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....

  10. 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...

  11. Use of regenerative energy sources and hydrogen technology 2006. Proceedings

    International Nuclear Information System (INIS)

    Lehmann, J.; Luschtinetz, T.

    2006-01-01

    This volume contains 25 contributions, which were held on the 13th symposium ''Use of regenerative energy sources and hydrogen technology'' in Stralsund (Germany). Separate documentation items analysing 16 of the contributions have been prepared for the ENERGY database

  12. 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

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. An overview of periodontal regenerative procedures for the general dental practitioner

    Directory of Open Access Journals (Sweden)

    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

  19. Bifunctional electrodes for unitised regenerative fuel cells

    International Nuclear Information System (INIS)

    Altmann, Sebastian; Kaz, Till; Friedrich, Kaspar Andreas

    2011-01-01

    Research highlights: → Different oxygen electrode configurations for the operation in a unitised reversible fuel cell were tested. → Polarisation curves and EIS measurements were recorded. → The mixture of catalysts performs best for the present stage of electrode development. → Potential improvements for the different compositions are discussed. - Abstract: The effects of different configurations and compositions of platinum and iridium oxide electrodes for the oxygen reaction of unitised regenerative fuel cells (URFC) are reported. Bifunctional oxygen electrodes are important for URFC development because favourable properties for the fuel cell and the electrolysis modes must be combined into a single electrode. The bifunctional electrodes were studied under different combinations of catalyst mixtures, multilayer arrangements and segmented configurations with single catalyst areas. Distinct electrochemical behaviour was observed for both modes and can be explained on the basis of impedance spectroscopy. The mixture of both catalysts performs best for the present stage of electrode development. Also, the multilayer electrodes yielded good results with the potential for optimisation. The influence of ionic and electronic resistances on the relative performance is demonstrated. However, penalties due to cross currents in the heterogeneous electrodes were identified and explained by comparing the performance curves with electrodes composed of a single catalyst. Potential improvements for the different compositions are discussed.

  20. Recent advancements in regenerative dentistry: A review.

    Science.gov (United States)

    Amrollahi, Pouya; Shah, Brinda; Seifi, Amir; Tayebi, Lobat

    2016-12-01

    Although human mouth benefits from remarkable mechanical properties, it is very susceptible to traumatic damages, exposure to microbial attacks, and congenital maladies. Since the human dentition plays a crucial role in mastication, phonation and esthetics, finding promising and more efficient strategies to reestablish its functionality in the event of disruption has been important. Dating back to antiquity, conventional dentistry has been offering evacuation, restoration, and replacement of the diseased dental tissue. However, due to the limited ability and short lifespan of traditional restorative solutions, scientists have taken advantage of current advancements in medicine to create better solutions for the oral health field and have coined it "regenerative dentistry." This new field takes advantage of the recent innovations in stem cell research, cellular and molecular biology, tissue engineering, and materials science etc. In this review, the recently known resources and approaches used for regeneration of dental and oral tissues were evaluated using the databases of Scopus and Web of Science. Scientists have used a wide range of biomaterials and scaffolds (artificial and natural), genes (with viral and non-viral vectors), stem cells (isolated from deciduous teeth, dental pulp, periodontal ligament, adipose tissue, salivary glands, and dental follicle) and growth factors (used for stimulating cell differentiation) in order to apply tissue engineering approaches to dentistry. Although they have been successful in preclinical and clinical partial regeneration of dental tissues, whole-tooth engineering still seems to be far-fetched, unless certain shortcomings are addressed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Alkaline Materials and Regenerative Endodontics: A Review

    Directory of Open Access Journals (Sweden)

    Bill Kahler

    2017-12-01

    Full Text Available Periapical health is the primary goal of endodontic treatment in mature and immature teeth. In addition, the goals of treatment of immature teeth with arrested root development include root growth to length and maturation of the apex, as well as thickening of the canal wall. These goals are valid for immature teeth that have been subjected to trauma and dental caries or that are the result of developmental anomalies that expose the tooth to the risk of pulp necrosis and consequently result in the cessation of root maturation. Regenerative endodontic procedures (REPs have been described as a “paradigm shift” in the treatment of immature teeth with pulp necrosis and underdeveloped roots, as there is the potential for further root maturation and return of vitality. Treatment with REPs is advocated as the treatment of choice for immature teeth with pulp necrosis. REP protocols involve the use of alkaline biomaterials, primarily sodium hypochlorite, calcium hydroxide, mineral trioxide aggregates and Biodentine, and are the essential components of a successful treatment regimen.

  2. Regenerative periapical surgery: A case report

    Directory of Open Access Journals (Sweden)

    Sonam Bhandari

    2013-01-01

    Full Text Available Introduction: Periapical surgery is an important treatment alternative in the presence of a large periapical cyst. To achieve optimal healing and regeneration of the bone different bone substitutes can be used. Case Report: A 35 year old male patient reported with the soft diffuse swelling in anterior palatal region and drainings in us with 21 labially. He had a history of trauma 5 years back. The clinical and radiographic diagnosis of infected periapical cyst with 11,21; invasive cervical root resorption with 21 and internal root resorption with 11 was made. Endodontic treatment was performed with11,2 followed by periapical curettage. A picectomy and retrograde filling with white mineral trioxide aggregate (MTA was carried out with 11,21. The cervical resorption defect with 21 was restored with white MTA. Platelet rich fibrin (PRF was mixed with demineralised bone matrix (Osseograft and used as a regenerative biomaterial in the periapiacl defect. 14 months follow up shows satisfactory healing and regeneration of periapical region. Discussion: There is considerable clinical interest in using PRF alone or in combination with graft materials as it is a reservoir of many growth factors and have potential for accelerated soft-and hard tissue healing. PRF is a new generation of platelet concentrate, derived from patients own blood.

  3. Translation-coupling systems

    Science.gov (United States)

    Pfleger, Brian; Mendez-Perez, Daniel

    2013-11-05

    Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

  4. 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.

  5. Retrospective Review of Student Research Projects in a Canadian Master of Science in Physical Therapy Programme and the Perceived Impact on Advisors' Research Capacity, Education, Clinical Practice, Knowledge Translation, and Health Policy.

    Science.gov (United States)

    Lacey, Courtney; Scodras, Stephanie; Ardron, Julie; Sellan, Ryan; Garbaczewska, Martyna; O'Brien, Kelly K; Salbach, Nancy M

    2018-01-01

    Purpose: This study's aim was to characterize the nature of students' research conducted for a Master of Science in Physical Therapy (MScPT) degree programme at a Canadian university and evaluate the lead advisors' perspectives of its impact on their research capacity, education, clinical practice, knowledge translation, and health policy. Methods: We conducted a quantitative, cross-sectional, retrospective review of research reports from 2003 to 2014 to characterize the MScPT students' research and a quantitative, cross-sectional e-survey of lead research advisors to evaluate the impact of this research. Results: Data were abstracted from reports of 201 research projects completed between 2003 and 2014. Projects were conducted primarily in university-affiliated hospitals (41.6%) or the university's physical therapy department (41.1%), and the majority (52.5%) had a clinical focus. Of the 95 lead advisors of 201 projects, 59 advisors (response rate 62.1%) of 119 projects completed the survey questionnaire. The respondents most frequently identified clinical practice (45.1%) and advisors' research capacity (31.4%) as areas positively affected by the students' research. Conclusions: The MScPT students' research projects facilitate the conduct of extensive research internally and across affiliated hospitals. This research appears to advance not only clinical practice but also the ability of lead advisors to undertake research.

  6. 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

  7. Writing Through: Practising Translation

    Directory of Open Access Journals (Sweden)

    Joel Scott

    2010-05-01

    Full Text Available This essay exists as a segment in a line of study and writing practice that moves between a critical theory analysis of translation studies conceptions of language, and the practical questions of what those ideas might mean for contemporary translation and writing practice. Although the underlying preoccupation of this essay, and my more general line of inquiry, is translation studies and practice, in many ways translation is merely a way into a discussion on language. For this essay, translation is the threshold of language. But the two trails of the discussion never manage to elude each other, and these concatenations have informed two experimental translation methods, referred to here as Live Translations and Series Translations. Following the essay are a number of poems in translation, all of which come from Blanco Nuclear by the contemporary Spanish poet, Esteban Pujals Gesalí. The first group, the Live Translations consist of transcriptions I made from audio recordings read in a public setting, in which the texts were translated in situ, either off the page of original Spanish-language poems, or through a process very much like that carried out by simultaneous translators, for which readings of the poems were played back to me through headphones at varying speeds to be translated before the audience. The translations collected are imperfect renderings, attesting to a moment in language practice rather than language objects. The second method involves an iterative translation process, by which three versions of any one poem are rendered, with varying levels of fluency, fidelity and servility. All three translations are presented one after the other as a series, with no version asserting itself as the primary translation. These examples, as well as the translation methods themselves, are intended as preliminary experiments within an endlessly divergent continuum of potential methods and translations, and not as a complete representation of

  8. 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.

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

    NARCIS (Netherlands)

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

    2016-01-01

    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

  10. 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.

  11. 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.

  12. 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.

  13. Why Translation Is Difficult

    DEFF Research Database (Denmark)

    Carl, Michael; Schaeffer, Moritz Jonas

    2017-01-01

    The paper develops a definition of translation literality that is based on the syntactic and semantic similarity of the source and the target texts. We provide theoretical and empirical evidence that absolute literal translations are easy to produce. Based on a multilingual corpus of alternative...... translations we investigate the effects of cross-lingual syntactic and semantic distance on translation production times and find that non-literality makes from-scratch translation and post-editing difficult. We show that statistical machine translation systems encounter even more difficulties with non-literality....

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

    Science.gov (United States)

    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.

  15. 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 ...

  16. Molecular Profiling to Optimize Treatment in Non-Small Cell Lung Cancer: A Review of Potential Molecular Targets for Radiation Therapy by the Translational Research Program of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.; Choy, Hak; Dicker, Adam P.; Saha, Debabrata; Simko, Jeff; Story, Michael D.; Torossian, Artour; Lu, Bo

    2012-01-01

    Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growth factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.

  17. Lost in translation? How adults living with Cystic Fibrosis understand treatment recommendations from their healthcare providers, and the impact on adherence to therapy.

    Science.gov (United States)

    Pakhale, S; Baron, J; Armstrong, M; Tasca, G; Gaudet, E; Aaron, S D; Cameron, W; Balfour, L

    2016-08-01

    This study builds on the limited research documenting Cystic Fibrosis (CF) patients' understanding of treatment recommendations and how this may impact adherence to therapy. We surveyed adults with CF and their healthcare professional (HCP) to capture treatment recommendations provided by the HCP, and patients' knowledge, and frequency of performance, of these recommendations. We classified CF participants' understanding of treatment recommendations (correct/incorrect) as compared to the actual recommendations made by the HCP. We computed CF participants' adherence in relation to HCP treatment recommendations and to their own understanding of treatment recommendations (adherent/non-adherent). Complete HCP and patient data were available for 42 participants. The recommended treatment frequency was correctly understood by 0%-87.8% of CF participants. Adherence to HCP treatment recommendations ranged from 0 to 68.3% (mean 45.4%±21.5), and rates were low (<33%) for acapella, percussion/postural drainage, tobramycin nebulization and insulin. Participants' adherence was greater when calculated in relation to participants' understanding of treatment recommendations (62.4%±25.1) than when calculated in relation to actual HCP treatment recommendations (45.4%±21.5%) (p=0.009). Adults with CF misunderstand treatment recommendations; this likely affects treatment adherence. Interventions to ensure HCPs use effective communication strategies are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Cognitive Behaviour Therapy for Bulimia Nervosa and Eating Disorders Not Otherwise Specified: Translation from Randomized Controlled Trial to a Clinical Setting.

    Science.gov (United States)

    Knott, Sarah; Woodward, Debbie; Hoefkens, Antonia; Limbert, Caroline

    2015-11-01

    Enhanced Cognitive Behaviour Therapy (CBT-E) (Fairburn, Cooper and Shafran, 2003) was developed as a treatment approach for eating disorders focusing on both core psychopathology and additional maintenance mechanisms. To evaluate treatment outcomes associated with CBT-E in a NHS Eating Disorders Service for adults with bulimia and atypical eating disorders and to make comparisons with a previously published randomized controlled trial (Fairburn et al., 2009) and "real world" evaluation (Byrne, Fursland, Allen and Watson, 2011). Participants were referred to the eating disorder service between 2002 and 2011. They were aged between 18-65 years, registered with a General Practitioner within the catchment area, and had experienced symptoms fulfilling criteria for BN or EDNOS for a minimum of 6 months. CBT-E was commenced by 272 patients, with 135 completing treatment. Overall, treatment was associated with significant improvements in eating disorder and associated psychopathology, for both treatment completers and the intention to treat sample. Findings support dissemination of CBT-E in this context, with significant improvements in eating disorder psychopathology. Improvements to global EDE-Q scores were higher for treatment completers and lower for the intention to treat sample, compared to previous studies (Fairburn et al., 2009; Byrne et al., 2011). Level of attrition was found at 40.8% and non-completion of treatment was associated with higher levels of anxiety. Potential explanations for these findings are discussed.

  19. Regenerative agriculture: merging farming and natural resource conservation profitably.

    Science.gov (United States)

    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.

  20. 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.

  1. Determinants of translation ambiguity

    Science.gov (United States)

    Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

    2016-01-01

    Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188

  2. Translation in ESL Classes

    Directory of Open Access Journals (Sweden)

    Nagy Imola Katalin

    2015-12-01

    Full Text Available The problem of translation in foreign language classes cannot be dealt with unless we attempt to make an overview of what translation meant for language teaching in different periods of language pedagogy. From the translation-oriented grammar-translation method through the complete ban on translation and mother tongue during the times of the audio-lingual approaches, we have come today to reconsider the role and status of translation in ESL classes. This article attempts to advocate for translation as a useful ESL class activity, which can completely fulfil the requirements of communicativeness. We also attempt to identify some activities and games, which rely on translation in some books published in the 1990s and the 2000s.

  3. Translation and Quality Management

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    1996-01-01

    theory which would seem likely to be of interest in this connection and section 2. gives a linguist's introduction to the part of the area of quality management which I consider relevant for present purposes. Section 3. is devoted to the case study of a small translation firm which has been certified......The aim of this article is to consider the issue of quality in translation. Specifically, the question under consideration is whether quality assurance in relation to translation is feasible and, if so, what some of the implications for translation theory, translation practice and the teaching...... of translation would be. To provide a backdrop against which the issue may be discussed, I present an overview of the two areas which seem most likely to hold potential answers, viz., that of translation theory and that of quality management. Section 1. gives a brief outline of some contributions to translation...

  4. Translation of cell therapy into clinical practice: validation of an application procedure for bone marrow progenitor cells and platelet rich plasma.

    Science.gov (United States)

    Nowotny, Joerg; Farack, Jana; Vater, Corina; Johnsen, Matthias; Gelinsky, Michael; Tonn, Torsten; Kasten, Philip

    2016-04-06

    Tissue regeneration can be improved by local application of autologous bone marrow derived progenitor cells (BMSC) and platelet rich plasma (PRP). However, there is a lack of standardized application procedures for clinical use. Therefore, a technique in accordance with the guidelines for advanced therapies medical products of the European Medicine Agency was developed and established. In detail, a process for the isolation and formulation of autologous bone marrow cells (BMC) and PRP in a clinical setting was validated. To investigate the influence of storage time and temperature on gel formation and gel stability, different concentrations of BMC were stored with and without additional platelets, thrombin and fibrinogen and analyzed over a period of 28 days. In addition, cell vitality using a live-dead staining and migration ability of human mesenchymal stem cells (hMSC) in the gel clot was investigated. For an optimized stable gel clot, human BMC and PRP should be combined with 10% to 20% fibrinogen (9 mg/mL to 18 mg/mL) and 5% to 20% thrombin (25 I.E. to 100 I.E.). Both freshly prepared and stored cells for 1 to 7 days had a stable consistence over 28 days at 37°C. Different platelet concentrations did not influence gel clot formation. The ratio of living cells did not decrease significantly over the observation period of 5 days in the live-dead staining. The study identified an optimal gel texture for local application of BMC and PRP. Seeded hMSC could migrate therein and were able to survive to initiate a healing cascade.

  5. Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

    Science.gov (United States)

    de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

    2018-04-01

    Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  6. Memetics and Translation Studies

    OpenAIRE

    Andrew, Chesterman

    2000-01-01

    Translation Studies is a branch of memetics. This is a claim, a hypothesis. More specifically, it is an interpretive hypothesis: I claim that Translation Studies can be thus interpreted, and that this is a useful thing to do because it offers a new and beneficial way of understanding translation.

  7. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2015-01-01

    ), Translog was employed to measure task times. The quality of the products was assessed by three experienced translators, and the number and types of misrecognitions were identified by a phonetician. Results indicate that SR translation provides a potentially useful supplement to written translation...

  8. 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.)

  9. 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.)

  10. Erich Regener and the ionisation maximum of the atmosphere

    Science.gov (United States)

    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.

  11. 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.

  12. 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.

  13. Human umbilical cord mesenchymal stromal cells in regenerative medicine.

    Science.gov (United States)

    Detamore, Michael S

    2013-11-25

    Cells of the human umbilical cord offer tremendous potential for improving human health. Cells from the Wharton’s jelly (umbilical cord stroma) in particular, referred to as human umbilical cord mesenchymal stromal cells (HUCMSCs), hold several advantages that make them appealing for translational research. In the previous issue of Stem Cell Research & Therapy, Chon and colleagues made an important contribution to the HUCMSC literature not only by presenting HUCMSCs as an emerging cell source for intervertebral disc regeneration in general and the nucleus pulposus in particular, but also by demonstrating that an extracellular matrix-based strategy might be preferred over the use of growth factors. By culturing HUCMSCs under hypoxia in serum-free conditions in the presence of Matrigel with laminin-111, they were able to achieve intense collagen II staining by 21 days without the addition of exogenous growth factors. There is tremendous translational significance here in that such raw materials may alleviate the need for the use of growth factors in some instances, and this may have important ramifications in reducing product cost and streamlining regulatory approval. Chon and colleagues provide a promising example of the potential of HUCMSCs, demonstrating the ability to guide HUCMSC differentiation even in the absence of serum and growth factors and supporting the use of HUCMSCs as a viable alternative in intervertebral disc regeneration.

  14. The Temple Translator's Workstation Project

    National Research Council Canada - National Science Library

    Vanni, Michelle; Zajac, Remi

    1996-01-01

    .... The Temple Translator's Workstation is incorporated into a Tipster document management architecture and it allows both translator/analysts and monolingual analysts to use the machine- translation...

  15. 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.

  16. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2013-01-01

    On the basis of a pilot study using speech recognition (SR) software, this paper attempts to illustrate the benefits of adopting an interdisciplinary approach in translator training. It shows how the collaboration between phoneticians, translators and interpreters can (1) advance research, (2) have......), Translog was employed to measure task times. The quality of the products was assessed by three experienced translators, and the number and types of misrecognitions were identified by a phonetician. Results indicate that SR translation provides a potentially useful supplement to written translation...

  17. Lost in translation

    DEFF Research Database (Denmark)

    Hedegaard, Steffen; Simonsen, Jakob Grue

    2011-01-01

    of translated texts. Our results suggest (i) that frame-based classifiers are usable for author attribution of both translated and untranslated texts; (ii) that framebased classifiers generally perform worse than the baseline classifiers for untranslated texts, but (iii) perform as well as, or superior...... to the baseline classifiers on translated texts; (iv) that—contrary to current belief—naïve classifiers based on lexical markers may perform tolerably on translated texts if the combination of author and translator is present in the training set of a classifier....

  18. Speaking your Translation

    DEFF Research Database (Denmark)

    Dragsted, Barbara; Mees, Inger M.; Gorm Hansen, Inge

    2011-01-01

    In this article we discuss the translation processes and products of 14 MA students who produced translations from Danish (L1) into English (L2) under different working conditions: (1) written translation, (2) sight translation, and (3) sight translation with a speech recognition (SR) tool. Audio......, since students were dictating in their L2, we looked into the number and types of error that occurred when using the SR software. Items that were misrecognised by the program could be divided into three categories: homophones, hesitations, and incorrectly pronounced words. Well over fifty per cent...

  19. Lost in translation?

    DEFF Research Database (Denmark)

    Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

    2014-01-01

    OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim...... of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? METHODS: Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences...... and ambiguities in the 5-point Likert scale and the BMQ statements were compared. RESULTS: In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward...

  20. What is a translator?

    Directory of Open Access Journals (Sweden)

    Martha Pulido

    2016-08-01

    Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

  1. What is a translator?

    Directory of Open Access Journals (Sweden)

    Martha Martha Pulido

    2016-05-01

    Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Platelet concentrates: Bioengineering dentistry′s regenerative dreams

    Directory of Open Access Journals (Sweden)

    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.

  8. 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)

  9. 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.

  10. 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.

  11. Discourse Analysis in Translator Training

    OpenAIRE

    Gülfidan Ayvaz

    2015-01-01

    Translator training enables students to gain experience in both linguistic parameters and translation practice. Discourse Analysis is one of the strategies that lead to a better translation process and quality in translation. In that regard, this study aims to present DA as a translation strategy for translation practice and a useful tool for translator training. The relationship between DA and Translator Training is not widely studied. Therefore this study aims to define DA and how it can be...

  12. The DARE study of relapse prevention in depression: design for a phase 1/2 translational randomised controlled trial involving mindfulness-based cognitive therapy and supported self monitoring

    Directory of Open Access Journals (Sweden)

    Shawyer Frances

    2012-01-01

    Full Text Available Abstract Background Depression is a common condition that typically has a relapsing course. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of the condition. Mindfulness-based cognitive therapy (MBCT is a group-based intervention that has shown efficacy in reducing depressive relapse. While trials of MBCT to date have met the core requirements of phase 1 translational research, there is a need now to move to phase 2 translational research - the application of MBCT within real-world settings with a view to informing policy and clinical practice. The aim of this trial is to examine the clinical impact and health economics of MBCT under real-world conditions and where efforts have been made to assess for and prevent resentful demoralization among the control group. Secondary aims of the project involve extending the phase 1 agenda to an examination of the effects of co-morbidity and mechanisms of action. Methods/Design This study is designed as a prospective, multi-site, single-blind, randomised controlled trial using a group comparison design between involving the intervention, MBCT, and a self-monitoring comparison condition, Depression Relapse Active Monitoring (DRAM. Follow-up is over 2 years. The design of the study indicates recruitment from primary and secondary care of 204 participants who have a history of 3 or more episodes of Major Depression but who are currently well. Measures assessing depressive relapse/recurrence, time to first clinical intervention, treatment expectancy and a range of secondary outcomes and process variables are included. A health economics evaluation will be undertaken to assess the incremental cost of MBCT. Discussion The results of this trial, including an examination of clinical, functional and health economic outcomes, will be used to assess the role that this treatment approach may have in recommendations for treatment of depression in Australia and

  13. 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

  14. 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.

  15. Struggling with Translations

    DEFF Research Database (Denmark)

    Obed Madsen, Søren

    This paper shows empirical how actors have difficulties with translating strategy texts. The paper uses four cases as different examples of what happens, and what might be difficult, when actors translate organizational texts. In order to explore this, it draws on a translation training method from...... translation theory. The study shows that for those who have produced the text, it is difficult to translate a strategy where they have to change the words so others who don’t understand the language in the text can understand it. It also shows that for those who haven’t been a part of the production, it very...... challenge the notion that actors understand all texts and that managers per se can translate a text....

  16. Translational ecology for hydrogeology.

    Science.gov (United States)

    Schlesinger, William H

    2013-01-01

    Translational ecology--a special discipline aimed to improve the accessibility of science to policy makers--will help hydrogeologists contribute to the solution of pressing environmental problems. Patterned after translational medicine, translational ecology is a partnership to ensure that the right science gets done in a timely fashion, so that it can be communicated to those who need it. © 2013, National Ground Water Association.

  17. Translation and Intertextuality

    Directory of Open Access Journals (Sweden)

    Mohammad Rahimi

    2015-09-01

    Full Text Available This study is intends to describe and Presents a new theory of translation based on the "Intertextuality" unlike the Translation theories that presented to date, what all are based on the principle of "Equivalence". Our theory is based on the examples of Arabic poetry translated into Persian poetry. The major findings of this study show that the Intertextuality can serve as a link between the original text and the target. it can also interact with other texts is the translation result in the target language, Whtich is the book of poetic eloquence is addressed and was mentioned Literary robbery.

  18. 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

  19. Mechanical cues in orofacial tissue engineering and regenerative medicine

    NARCIS (Netherlands)

    Brouwer, K.M.; Lundvig, D.M.S.; Middelkoop, E.; Wagener, F.A.D.T.; Von den Hoff, J.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

  20. CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges.

    Science.gov (United States)

    Jamieson, Catriona H M; Millan, Maria T; Creasey, Abla A; Lomax, Geoff; Donohoe, Mary E; Walters, Mark C; Abedi, Mehrdad; Bota, Daniela A; Zaia, John A; Adams, John S

    2018-06-01

    The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Kwantificatie van de invloed van regen op de verkeerdoorstroming

    NARCIS (Netherlands)

    Calvert, S.C.; Van Stralen, W.; Molin, E.J.E.

    2013-01-01

    Kwantificatie van de invloed van regen op de verkeerdoorstroming Het is bekend dat het weer invloed heeft op het verkeer op snelwegen, en in het bijzonder filevorming. Op de eerste plaats wordt de wegcapaciteit tijdelijk beïnvloed door een verandering in rijgedrag van bestuurders. Ten tweede

  2. Stem cell bioprinting for applications in regenerative medicine.

    Science.gov (United States)

    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.

  3. 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.

  4. Conditional approval: Japan lowers the bar for regenerative medicine products.

    Science.gov (United States)

    Sipp, Douglas

    2015-04-02

    A new system for conditional approval of regenerative medicine products will allow products of undetermined efficacy to enter the Japanese market. The potential scientific, economic, and ethical implications of this program highlight the need for further discussion and refinement. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 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.

  6. 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,

  7. 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

  8. 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.

  9. Endothelial-Mesenchymal Transition in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Damian Medici

    2016-01-01

    Full Text Available Endothelial-mesenchymal transition (EndMT is a fundamental cellular mechanism that regulates embryonic development and diseases such as cancer and fibrosis. Recent developments in biomedical research have shown remarkable potential to harness the EndMT process for tissue engineering and regeneration. As an alternative to traditional or artificial stem cell therapies, EndMT may represent a safe method for engineering new tissues to treat degenerative diseases by mimicking a process that occurs in nature. This review discusses the signaling mechanisms and therapeutic inhibitors of EndMT, as well as the role of EndMT in development, disease, acquiring stem cell properties and generating connective tissues, and its potential as a novel mechanism for tissue regeneration.

  10. 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...

  11. Livestock models in translational medicine.

    Science.gov (United States)

    Roth, James A; Tuggle, Christopher K

    2015-01-01

    This issue of the ILAR Journal focuses on livestock models in translational medicine. Livestock models of selected human diseases present important advantages as compared with rodent models for translating fundamental breakthroughs in biology to useful preventatives and therapeutics for humans. Livestock reflect the complexity of applying medical advances in an outbred species. In many cases, the pathogenesis of infectious, metabolic, genetic, and neoplastic diseases in livestock species more closely resembles that in humans than does the pathogenesis of rodent models. Livestock models also provide the advantage of similar organ size and function and the ability to serially sample an animal throughout the study period. Research using livestock models for human disease often benefits not only human health but animal health and food production as well. This issue of the ILAR Journal presents information on translational research using livestock models in two broad areas: microbiology and infectious disease (transmissible spongiform encephalopathies, mycobacterial infections, influenza A virus infection, vaccine development and testing, the human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular dystrophy, wound healing). In addition, there is a manuscript devoted to Institutional Animal Care and Use Committees' responsibilities for reviewing research using livestock models. Conducting translational research using livestock models requires special facilities and researchers with expertise in livestock. There are many institutions in the world with experienced researchers and facilities designed for livestock research; primarily associated with colleges of agriculture and veterinary medicine or government laboratories. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions

  12. Lost in Translation?

    NARCIS (Netherlands)

    Jonkers, Peter

    2017-01-01

    Translating sacred scriptures is not only a praxis that is crucial for the fruitful, i.e. non-distorted and unbiased dialogue between different religious traditions, but also raises some fundamental theoretical questions when it comes to translating the sacred texts of the religious other or

  13. Translating VDM to Alloy

    DEFF Research Database (Denmark)

    Lausdahl, Kenneth

    2013-01-01

    specifications. However, to take advantage of the automated analysis of Alloy, the model-oriented VDM specifications must be translated into a constraint-based Alloy specifications. We describe how a sub- set of VDM can be translated into Alloy and how assertions can be expressed in VDM and checked by the Alloy...

  14. Students' Differentiated Translation Processes

    Science.gov (United States)

    Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla

    2014-01-01

    Understanding how students translate between mathematical representations is of both practical and theoretical importance. This study examined students' processes in their generation of symbolic and graphic representations of given polynomial functions. The purpose was to investigate how students perform these translations. The result of the study…

  15. Creativity, Culture and Translation

    Science.gov (United States)

    Babaee, Siamak; Wan Yahya, Wan Roselezam; Babaee, Ruzbeh

    2014-01-01

    Some scholars (Bassnett-McGuire, Catford, Brislin) suggest that a good piece of translation should be a strict reflection of the style of the original text while some others (Gui, Newmark, Wilss) consider the original text untranslatable unless it is reproduced. Opposing views by different critics suggest that translation is still a challenging…

  16. Translation as (Global) Writing

    Science.gov (United States)

    Horner, Bruce; Tetreault, Laura

    2016-01-01

    This article explores translation as a useful point of departure and framework for taking a translingual approach to writing engaging globalization. Globalization and the knowledge economy are putting renewed emphasis on translation as a key site of contest between a dominant language ideology of monolingualism aligned with fast capitalist…

  17. Measuring Translation Literality

    DEFF Research Database (Denmark)

    Carl, Michael; Schaeffer, Moritz

    2017-01-01

    Tirkkonen-Condit (2005: 407–408) argues that “It looks as if literal translation is [the result of] a default rendering procedure”. As a corollary, more literal translations should be easier to process, and less literal ones should be associated with more cognitive effort. In order to assess this...

  18. Text Coherence in Translation

    Science.gov (United States)

    Zheng, Yanping

    2009-01-01

    In the thesis a coherent text is defined as a continuity of senses of the outcome of combining concepts and relations into a network composed of knowledge space centered around main topics. And the author maintains that in order to obtain the coherence of a target language text from a source text during the process of translation, a translator can…

  19. TRANSLATING SERVICE TECHNICAL PROSE

    African Journals Online (AJOL)

    language. The Application of Technical Service. Prose. To form a good idea of the appl ication .... cost lives. In this particular domain, translators must have a sound technical ... These semantic ... another language and often, in doing so, changing its meaning. The words ..... He will hand out tasks to each translator and after.

  20. Stimulating translational research

    DEFF Research Database (Denmark)

    Bentires-Alj, Mohamed; Rajan, Abinaya; van Harten, Wim

    2015-01-01

    Translational research leaves no-one indifferent and everyone expects a particular benefit. We as EU-LIFE (www.eu-life.eu), an alliance of 13 research institutes in European life sciences, would like to share our experience in an attempt to identify measures to promote translational research with...... without undermining basic exploratory research and academic freedom....