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      Pluripotent stem cells progressing to the clinic

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      Nature Reviews Molecular Cell Biology

      Springer Science and Business Media LLC

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          Abstract

          Basic experimental stem cell research has opened up the possibility of many diverse clinical applications; however, translation to clinical trials has been restricted to only a few diseases. To broaden this clinical scope, pluripotent stem cell derivatives provide a uniquely scalable source of functional differentiated cells that can potentially repair damaged or diseased tissues to treat a wide spectrum of diseases and injuries. However, gathering sound data on their distribution, longevity, function and mechanisms of action in host tissues is imperative to realizing their clinical benefit. The large-scale availability of treatments involving pluripotent stem cells remains some years away, because of the long and demanding regulatory pathway that is needed to ensure their safety.

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          Most cited references 62

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          Generation of functional human pancreatic β cells in vitro.

          The generation of insulin-producing pancreatic β cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide β cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem-cell-derived β cells (SC-β) express markers found in mature β cells, flux Ca(2+) in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells.

            Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic beta cells, including MAFA, and displayed glucose-stimulated insulin secretion similar to that of human islets during static incubations in vitro. Additional characterization using single-cell imaging and dynamic glucose stimulation assays revealed similarities but also notable differences between S7 insulin-secreting cells and primary human beta cells. Nevertheless, S7 cells rapidly reversed diabetes in mice within 40 days, roughly four times faster than pancreatic progenitors. Therefore, although S7 cells are not fully equivalent to mature beta cells, their capacity for glucose-responsive insulin secretion and rapid reversal of diabetes in vivo makes them a promising alternative to pancreatic progenitor cells or cadaveric islets for the treatment of diabetes.
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              Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

              The Lancet, 385(9967), 509-516
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                Author and article information

                Journal
                Nature Reviews Molecular Cell Biology
                Nat Rev Mol Cell Biol
                Springer Science and Business Media LLC
                1471-0072
                1471-0080
                March 2016
                February 23 2016
                March 2016
                : 17
                : 3
                : 194-200
                Article
                10.1038/nrm.2016.10
                26908143
                © 2016

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