|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Authentication of human cell-based products: the role of a new consensus standard. Regen Med. 2011 Mar;6(2):255-60 Authors: Kerrigan L, Nims RW Authentication of human tissues, cell lines and primary cell cultures (including stem cell preparations) used as therapeutic modalities is often performed using phenotyping and technologies capable of assessing identity to the species level (e.g., isoenzyme analysis and/or karyotyping). This authentication paradigm alone cannot provide assurance that the correct human cell preparation is administered, so careful labeling and tracking of cells from the donor, during manufacture and as part of the final product are also employed. Precise, accurate identification of human cells to the individual donor level could, however, significantly reduce the risks of exposing human subjects to misidentified cells. The availability of a standardized method for achieving this will provide a way to improve the safety profile of human cell-based products by providing assurance that a given lot of cells originated from the intended donor and were not inadvertently mixed or replaced with cells from other donors. In support of this goal, an international team of scientists has prepared a consensus standard on authentication of human cells using short tandem repeat profiling. Associated with the standard itself will be the establishment and maintenance of a public database of short tandem repeat profiles for commonly used cell lines. PMID: 21391858 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells from adipose tissue. Cell Mol Biol Lett. 2011 Mar 9; Authors: Witkowska-Zimny M, Walenko K This is a review of the growing scientific interest in the developmental plasticity and therapeutic potential of stromal cells isolated from adipose tissue. Adipose-derived stem/stromal cells (ASCs) are multipotent somatic stem cells that are abundant in fat tissue. It has been shown that ASCs can differentiate into several lineages, including adipose cells, chondrocytes, osteoblasts, neuronal cells, endothelial cells, and cardiomyocytes. At the same time, adipose tissue can be harvested by a minimally invasive procedure, which makes it a promising source of adult stem cells. Therefore, it is believed that ASCs may become an alternative to the currently available adult stem cells (e.g. bone marrow stromal cells) for potential use in regenerative medicine. In this review, we present the basic information about the field of adipose-derived stem cells and their potential use in various applications. PMID: 21394447 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hyaluronic Acid Hydrogels for Biomedical Applications. Adv Mater. 2011 Mar 10; Authors: Burdick JA, Prestwich GD Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms-viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids-for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications. PMID: 21394792 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Institutional Profile: The International Society for Cellular Therapy: evolving to meet the demands of the regenerative medicine industry. Regen Med. 2011 Mar;6(2):163-6 Authors: Maziarz RT, Arthurs J, Horwitz E The International Society for Cellular Therapy is a global association driving the translation of scientific research to deliver innovative cellular therapies to patients. Established in 1992, its membership and leadership comprises world-class scientists, clinicians, technologists, biotech/pharma and regulatory professionals from 40 countries focused on preclinical and translational aspects of developing cell therapy products. The International Society for Cellular Therapy has evolved in alignment with the maturation of the field of cell therapy and regenerative medicine to create forums for discussion of shared concerns for commercialization of cell therapies and of development of consensus standards, recognizing that true commercialization depends upon the translational scientific community, the regional regulatory and policy institutions, and the technology support and capital investment from industry. It exists to facilitate the international work of many, to spawn new initiatives, and to synergize with other stakeholders to create the best outcome for the many patients across the world depending on the answers and improved health that cellular therapeutics will provide them. PMID: 21391849 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Industry Update: Latest developments in stem cell research and regenerative medicine. Regen Med. 2011 Mar;6(2):145-56 Authors: Ilic D PMID: 21391847 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiac tumorgenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. Regen Med. 2011 Mar;6(2):171-8 Authors: Ahmed RP, Ashraf M, Buccini S, Shujia J, Haider HKh Aim: Genetic reprogramming of somatic cells with stemness genes to restore their pluripotent status is being studied extensively to generate pluripotent stem cells as an alternative to embryonic stem cells. This study was designed to examine the effectiveness of skeletal myoblast-derived induced pluripotent stem cells (SkiPS) from young male Oct4/GFP transgenic mice for regeneration of the infarcted heart. Methods & results: A mouse model of permanent coronary artery ligation was developed in young female immunocompetent C57BL/6J or C57BL/6x129S4 SV/jae Oct4/GFP mice. SkiPS labeled with Q-dots (3 × 10(5) in 10 µl basal Dulbecco's modified Eagle's medium) were transplanted in and around the area of infarct immediately after coronary artery ligation (n = 16) under direct vision. Control mice (n = 12) were injected with the same number of skeletal myoblasts. Histological studies documented successful engraftment of SkiPS in all the surviving animals 4 weeks later. However, six of the 16 SkiPS-transplanted (37.5%) animal hearts showed intramural teratomas, whereas no tumor growth was observed in the control mice. Q-dot-labeled donor cells were also observed at the site of tumors. Histological studies revealed that teratomas were composed of cells from all of the three embryonic germ layers. Ultra-structure studies confirmed the histological findings and showed regions with well-organized myofibrillar structures in the tumors. Conclusion: Undifferentiated induced pluripotent stem cells should not be recommended for cardiac transplantation unless screened for specific teratogenic precursors or predifferentiated into cardiac lineage prior to transplantation. PMID: 21391851 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Intravenous administration of bone marrow mesenchymal stromal cells is safe for the lung in a chronic myocardial infarction model. Regen Med. 2011 Mar;6(2):179-90 Authors: Wang W, Jiang Q, Zhang H, Jin P, Yuan X, Wei Y, Hu S Aims: Intravenous administration of bone marrow mesenchymal stromal cells (MSCs) is an attractive option for the treatment of myocardial infarction (MI). Previous studies revealed that MSC infusion could limit the deterioration of cardiac function following acute MI; however, little is known regarding the safety and efficacy of MSC infusion for chronic MI. In this study, we address cell retention after intravenous injection in a chronic MI model, and the fate and impact of distributed MSCs in the lung and heart. Methods: MI model was created by coronary ligation in female rats. A total of 3 weeks later, 5 × 10(6) bromodeoxyuridine-labeled male MSCs in 300 µl phosphate-buffered solution (PBS) were infused intravenously (cell transplantation group, n = 37). The same volume of PBS was infused and served as the control group (n = 37). A total of 20 healthy rats received intravenous PBS injections and served as the sham group. 1 day and 4 weeks after cell or PBS infusion, echocardiography was performed and cell retention was evaluated by quantitative real-time PCR. The fate of the migrated cells was detected through immunohistochemistry and the expression of inflammatory and anti-inflammatory protein was evaluated in lung and heart. The lung and heart function was also assessed. Results: 1 day after cell implantation, the percentage of retained cells relative to the initial number of injected cells in heart and lung was 0.54 ± 0.19% and 51.69 ± 12.96%, respectively. After 4 weeks, it decreased to 0.24 ± 0.09% and 0.22 ± 0.17%. The entrapped MSCs did not differentiate into alveolar epithelial-like cells. Likewise, the left ventricular function was not improved. No adverse effects on lung function were observed after cell infusion. The expression of pro-inflammatory factors, including TNF-α, IL-1β, malondialdehyde and myeloperoxidase, and anti-inflammatory factors, including TNF-α-induced protein 6, in the lung and heart was not significantly regulated after cell transplantation. Conclusion: Although the majority of intravenous infused cells were harbored in the lung, they did not cause deterioration of lung function. However, they did not activate the release of inflammatory/anti-inflammatory proteins, or stimulate angiogenesis or myogenesis in the old infarcted myocardium. Thus, intravenous administration of MSCs for chronic MI needs further experimental study. PMID: 21391852 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Embryonic stem cell extracts: use in differentiation and reprogramming. Regen Med. 2011 Mar;6(2):215-27 Authors: Han J, Sidhu K Stem cells have been studied extensively for decades and they have the inherent capacity to self-renew as well as to generate one or more types of specialized cells. The current focus of research on stem cells, particularly on embryonic stem cells, is on directed differentiation of these cells into specific cell types for future regenerative medicine. For the past few years, the process of reprogramming, which mediates convertion of somatic cells to their pluripotent state, has been given much attention, as it provides a possible source of autologous stem cells. In addition, understanding the molecular mechanism of differentiation and reprogramming has long been a subject of interest. In this article, we have briefly introduced stem cells and discussed the use of embryonic stem cells in reprogramming of somatic cells and differentiation to different lineages. The application of embryonic stem cells extracts in inducing reprogramming and transdifferentiation has also been described and discussed. Should this approach be successful, patient-specific cells will be produced safely and the likelihood of rejection will be decreased when used in cell therapy for many debilitating human diseases for which there is no cure such as Parkinson's disease, Alzheimer's disease, diabetes and others. PMID: 21391855 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Coordination of fingertip forces during precision grip in premanifest Huntington's disease. Mov Disord. 2011 Mar 10; Authors: Rao AK, Gordon AM, Marder KS Precision grip control is important for accurate object manipulation and requires coordination between horizontal (grip) and vertical (load) fingertip forces. Manifest Huntington's disease (HD) subjects demonstrate excessive and highly variable grip force and delayed coordination between grip and load forces. Because the onset of these impairments is unknown, we examined precision grip control in premanifest HD (pre-HD) subjects. Fifteen pre-HD and 15 age- and sex-matched controls performed the precision grip task in a seated position. Subjects grasped and lifted an object instrumented with a force transducer that measured horizontal grip and vertical load forces. Outcomes were preload time, loading time, maximum grip force, mean static grip force, and variability for all measures. We compared outcomes across groups and correlated grip measures with the Unified Huntington's Disease Rating Scale and predicted age of onset. Variability of maximum grip force (P < .0001) and variability of static grip force (P < .00001) were higher for pre-HD subjects. Preload time (P < .007) and variability of preload time (P < .006) were higher in pre-HD subjects. No differences were seen in loading time across groups. Variability of static grip force (r(2) = 0.23) and variability of preload time (r(2) = 0.59) increased with predicted onset and were correlated with tests of cognitive function. Our results indicate that pre-HD patients have poor regulation of the transition between reach and grasp and higher variability in force application and temporal coordination during the precision grip task. Force and temporal variability may be good markers of disease severity because they were correlated with predicted onset of disease. © 2011 Movement Disorder Society. PMID: 21394785 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Role of mechanical factors in fate decisions of stem cells. Regen Med. 2011 Mar;6(2):229-40 Authors: Li D, Zhou J, Chowdhury F, Cheng J, Wang N, Wang F Stem cells derived from adult tissues or from the inner cell mass of blastocyst-stage embryos can self-renew in culture and have the remarkable potential to undergo lineage-specific differentiation. Extensive studies have been devoted to achieving a better understanding of the soluble factors and the mechanism(s) by which they regulate the fate decisions of these cells, but it is only recently that a critical role has been revealed for physical and mechanical factors in controlling self-renewal and lineage specification. This review summarizes selected aspects of current work on stem cell mechanics with an emphasis on the influence of matrix stiffness, surface topography, cell shape and mechanical forces on the fate determination of mesenchymal stem cells and embryonic stem cells. PMID: 21391856 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine, resource and regulation: lessons learned from the remedi project. Regen Med. 2011 Mar;6(2):241-53 Authors: Ginty PJ, Rayment EA, Hourd P, Williams DJ The successful commercialization of regenerative medicine products provides a unique challenge to the manufacturer owing to a lack of suitable investment/business models and a constantly evolving regulatory framework. The resultant slow translation of scientific discovery into safe and clinically efficacious therapies is preventing many potential products from reaching the market. This is despite of the need for new therapies that may reduce the burden on the world's healthcare systems and address the desperate need for replacement tissues and organs. The collaborative Engineering and Physical Sciences Research Council (EPSRC)-funded remedi project was devised to take a holistic but manufacturing-led approach to the challenge of translational regenerative medicine in the UK. Through strategic collaborations and discussions with industry and other academic partners, many of the positive and negative issues surrounding business and regulatory success have been documented to provide a remedi-led perspective on the management of risk in business and the elucidation of the regulatory pathways, and how the two are inherently linked. This article represents the findings from these discussions with key stakeholders and the research into best business and regulatory practices. PMID: 21391857 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Conference Scene: A bright future for tissue engineering and regenerative medicine in the Asia Pacific region. Regen Med. 2011 Mar;6(2):167-70 Authors: Frith JE, Hudson JE, Cooper-White JJ The Tissue Engineering and Regenerative Medicine International Society - Asia Pacific (TERMIS-AP) annual meeting was held in Sydney, Australia from 15-17 September 2010 and highlighted the latest developments in tissue engineering and regenerative medicine in the Asia-Pacific region. Several of the plenary lectures focused on the vascularization of tissue engineering constructs, an issue that is critical for the success of larger tissue engineered constructs and was central to the meeting overall. In addition, a wide range of research also presented developments in tissue engineering for a range of body tissues (including cardiac, neural, bone, cartilage, tendon, skeletal muscle and skin), as well as advances in technologies (high-throughput screening and microfluidics). Looking more broadly, the meeting incorporated developments covering the spectrum of fundamental research through to clinical studies, with discussions on how best to direct the scientific advances being made into realistic therapies that could be made widely available in the future. Overall, the meeting highlighted the promise of early strategies, which are now showing promising results in clinical trials, and the development of a strong foundation of research from which future therapies will no doubt be developed. PMID: 21391850 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells display different gene expression profiles compared to hyaline and elastic chondrocytes. Int J Clin Exp Med. 2011;4(1):81-90 Authors: Zhai LJ, Zhao KQ, Wang ZQ, Feng Y, Xing SC Cartilage has a poor intrinsic repair capacity, requiring surgical intervention to effect biological repair. Tissue engineering technologies or regenerative medicine strategies are currently being employed to address cartilage repair. Mesenchymal stem cells (MSCs) are considered to be an excellent cell source for this application. However, the different gene expression profiles between the MSCs and differentiated cartilage remain unclear. In this report, we first examined the gene expression profiles between the MSCs, hyaline and elastic chondrocytes, and then identify candidate genes, which may be important in the process of MSC differentiation into hyaline and elastic cartilage. Several hundred differentially expressed genes were screened initially by microarray, including 417 simultaneously up-regulated genes in both hyaline and elastic chondrocytes, with 313 down-regulated genes. Several genes were identified that were up-regulated in hyaline chondrocytes while down-regulated in elastic chondrocytes. Both RT-PCR and western blot analysis were consistent with those results obtained by microarray analysis. Chondromodulinl (Chm1) was found to be highly expressed in MSCs differentiating to hyaline and elastic cartilage. Both collagen type II, alpha 1 (Col2a1) and cartilage homeo protein 1 (Cart1) were also highly upregulated and may be important early differentiation of MSCs to hyaline cartilage. PMID: 21394289 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cell technology for the study and treatment of motor neuron diseases. Regen Med. 2011 Mar;6(2):201-13 Authors: Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL Amyotrophic lateral sclerosis and spinal muscular atrophy are devastating neurodegenerative diseases that lead to the specific loss of motor neurons. Recently, stem cell technologies have been developed for the investigation and treatment of both diseases. Here we discuss the different stem cells currently being studied for mechanistic discovery and therapeutic development, including embryonic, adult and induced pluripotent stem cells. We also present supporting evidence for the utilization of stem cell technology in the treatment of amyotrophic lateral sclerosis and spinal muscular atrophy, and describe key issues that must be considered for the transition of stem cell therapies for motor neuron diseases from bench to bedside. Finally, we discuss the first-in-human Phase I trial currently underway examining the safety and feasibility of intraspinal stem cell injections in amyotrophic lateral sclerosis patients as a foundation for translating stem cell therapies for various neurological diseases. PMID: 21391854 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Corrigendum. Regen Med. 2011 Mar;6(2):264 Authors: PMID: 21391860 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses. Int Orthop. 2011 Mar 11; Authors: Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R PURPOSE: Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to other therapies. METHODS: After ultrasonographic localisation of the lesion, the autologous BMMNC suspension and PRP were injected directly into the core lesion. BMMNC and platelet count as well as growth factors in PRP were measured to determine factors influencing the clinical outcome. RESULTS: Horses showed a marked improvement in their degree of lameness and 84.6% were able to return to competition. Among all the factors studied, the platelet concentration predicted the healing time: significantly faster recovery (p = 0.049) was observed in cases of PRP with more than 750 × 10(3)/μl platelets. CONCLUSIONS: Competition horses are involved in highly demanding activities, thus being a similar model for the high mechanical overload typical of human athletes. The promising results obtained suggest that this combined biological approach may be useful even for the treatment of recalcitrant overuse musculoskeletal injuries in highly demanding patients if the appropriate dose of cells and GFs is applied. PMID: 21394594 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Acknowledgements. Regen Med. 2011 Mar;6(2):261 Authors: PMID: 21391859 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Interview: The story of Advanced BioHealing: commercializing bioengineered tissue products. Regen Med. 2011 Mar;6(2):157-61 Authors: Tozer D Dean Tozer is Senior Vice President at Advanced BioHealing, Inc. (ABH), overseeing marketing, corporate development, government affairs, product development, various regulatory functions and international expansion. After completing his Bachelor of Commerce from Saint Mary's University in Halifax, Canada, Mr Tozer spent 10 years in the global pharmaceutical industry, primarily with G.D. Searle (a division of Monsanto) where he had a wide variety of roles in Global Marketing, Sales, Business Redesign, and Accounting and Finance. Mr Tozer then worked as a consultant to the biopharmaceutical industry, assisting start-up organizations in developing commercial strategies for both pharmaceutical products and biomedical devices, prior to joining ABH in March 2006 as Vice President of Marketing & Corporate Development. In addition to his leadership role at ABH, Mr Tozer currently serves as an officer and board member for the Alliance for Regenerative Medicine, a Washington DC-based organization formed to advance regenerative medicine by representing and supporting the community of companies, academic research institutions, patient advocacy groups, foundations, and other organizations before the Congress, federal agencies and the general public. PMID: 21391848 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Chitosan nanoparticles as a dual growth factor delivery system for tissue engineering applications. Int J Pharm. 2011 Mar 7; Authors: Rajam M, Pulavendran S, Rose C, Mandal AB Growth factors are essential in cellular signaling for migration, proliferation, differentiation and maturation. Sustainable delivery of therapeutic as well as functional proteins is largely required in the pharmacological and regenerative medicine. Here we have prepared chitosan nanoparticles (CNP) and incorporated growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), either individually or in combination, which could ultimately be impregnated into engineered tissue construct. CNP was characterized by fourier transform infrared spectroscopy (FTIR), Zeta sizer and high resolution transmission electron microscope (HRTEM). The particles were in the size range of 50-100nm with round and flat shape. The release kinetics of both EGF and FGF incorporated CNP showed the release of growth factors in a sustained manner. Growth factors incorporated nanoparticles did not show any toxicity against fibroblasts up to 4mg/ml culture medium. Increased proliferation of fibroblasts in vitro evidenced the delivery of growth factors from CNP for cellular signaling. Western blotting results also revealed the poor inflammatory response showing less expression of proinflammatory cytokines such as IL-6 and TNFα in the macrophage cell line J774 A-1. PMID: 21392563 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioengineering of dental stem cells in a PEGylated fibrin gel. Regen Med. 2011 Mar;6(2):191-200 Authors: Galler KM, Cavender AC, Koeklue U, Suggs LJ, Schmalz G, D'Souza RN Aim: Postnatal stem cells can generate tooth-specific structures after transplantation in vivo, which makes them a valuable tool for dental tissue engineering. Scaffold materials that are compatible with dental stem cells, injectable and tunable for targeted regeneration are needed. A candidate material is fibrin, a biopolymer critical to hemostasis and wound healing. Rapid degradation of fibrin can be decelerated by modification with polyethylene glycol (PEG), thus creating a hybrid material for cell delivery. The aim of this study was to evaluate the suitability of PEGylated fibrin as a scaffold for dental stem cells. Methods: A PEGylated fibrin hydrogel was combined with stem cells derived from dental pulp or periodontal ligament. Cell proliferation was assessed over a 4-week period, and alkaline phosphatase activity and expression levels of mineralization-associated genes after osteogenic induction were analyzed. Cell morphology, matrix degradation, collagen production and mineral deposition were evaluated by histology. Constructs of PEGylated fibrin with dental pulp stem cells in dentin disks were transplanted in immunocompromised mice for 5 weeks and examined for new tissue formation. Results: All cell types proliferated in PEGylated fibrin. After osteogenic induction, alkaline phosphatase activity was higher and osteoblast-specific genes were upregulated. Dentin-specific markers increased in pulp-derived stem cells. Histologic analysis revealed degradation of fibrin, production of a collagenous matrix and mineral deposition. In vivo transplantation rendered a vascularized soft connective tissue similar to dental pulp. Conclusion: Fibrin allows for the growth and differentiation of dental stem cells, can be inserted into small defects and thus appears to be a promising biomaterial for tissue regeneration in the oral cavity. PMID: 21391853 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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