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      New perspectives in human stem cell therapeutic research

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      1 ,
      BMC Medicine
      BioMed Central

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          Abstract

          Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action of many of these cells are unknown and this raises the concern of unpredictable results in the future. Nevertheless there is considerable optimism that immune suppression and anti-inflammatory properties of mesenchymal stem cells will be of benefit for many conditions such as graft versus host disease, solid organ transplants and pulmonary fibrosis. Where bone marrow and mesenchymal stem cells are being studied for heart disease, stroke and other neurodegenerative disorders, again progress is mixed and mostly without significant benefit. However, correction of multiple sclerosis, at least in the short term is encouraging. Clinical trials on the use of embryonic stem cell derivatives for spinal injury and macular degeneration are beginning and a raft of other clinical trials can be expected soon, for example, the use of neural stem cells for killing inoperable glioma and embryonic stem cells for regenerating β islet cells for diabetes. The change in attitude to embryonic stem cell research with the incoming Obama administration heralds a new co-operative environment for study and evaluation of stem cell therapies. The Californian stem cell initiative (California Institute for Regenerative Medicine) has engendered global collaboration for this new medicine that will now also be supported by the US Federal Government. The active participation of governments, academia, biotechnology, pharmaceutical companies, and private investment is a powerful consortium for advances in health.

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          Most cited references26

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          Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.

          Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional beta-cells, including expression of critical beta-cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell-derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.
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            Generation of induced pluripotent stem cells using recombinant proteins.

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              Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS): bridging basic and clinical science for cellular and neurogenic factor therapy in treating stroke.

              (2009)
              Investigators developing cellular therapy for stroke face many challenges. Preclinical models used for cellular therapy studies should be relevant to human stroke and predictive of benefit despite differences in stroke size, cerebrovascular anatomy, immune status, and neurological responses. Translating preclinical testing to human trials is compounded by consideration of delivery method and translation of dosing with cell survival. Many issues must be approached in designing clinical trials of cellular therapy for stroke, including appropriate outcome measures, controlling for confounding factors such as rehabilitation therapy, and possible surrogate outcomes using imaging such as MRI and newer imaging techniques. It is also important to establish standardized clinical protocols and clinical database registries in advance of early proof-of-concept studies. Investigators must adopt a standardized nomenclature and characterization schema for cell products to accurately define potency and determine clinical outcome from early proof-of-concept studies. The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.
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                Author and article information

                Journal
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2009
                11 June 2009
                : 7
                : 29
                Affiliations
                [1 ]California Institute for Regenerative Medicine, 210 King Street, San Francisco, CA, 94107, USA
                Article
                1741-7015-7-29
                10.1186/1741-7015-7-29
                2702289
                19519878
                f1930671-aa7f-4483-802b-3601bfd41792
                Copyright © 2009 Trounson; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 May 2009
                : 11 June 2009
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                Medicine
                Medicine

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