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      Human Embryonic and Induced Pluripotent Stem Cell Research Trends: Complementation and Diversification of the Field

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          Summary

          Research in human induced pluripotent stem cells (hiPSCs) is rapidly developing and there are expectations that this research may obviate the need to use human embryonic stem cells (hESCs), the ethics of which has been a subject of controversy for more than 15 years. In this study, we investigated approximately 3,400 original research papers that reported an experimental use of these types of human pluripotent stem cells (hPSCs) and were published from 2008 to 2013. We found that research into both cell types was conducted independently and further expanded, accompanied by a growing intersection of both research fields. Moreover, an in-depth analysis of papers that reported the use of both cell types indicates that hESCs are still being used as a “gold standard,” but in a declining proportion of publications. Instead, the expanding research field is diversifying and hESC and hiPSC lines are increasingly being used in more independent research and application areas.

          Highlights

          • Research in hESCs and hiPSCs has recently expanded, but to different extents

          • Research in hESCs and hiPSCs partially overlaps, but is also diversifying

          • The “gold standard” use of hESCs is relatively declining

          • Only a few hESC lines are predominantly used as a benchmark in hiPSC research

          Abstract

          In this article, Löser, Kobold, and colleagues investigate recent trends in research involving human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). They show that research has expanded during the past 6 years, and that research in hESCs and hiPSCs partially overlaps. However, they show that the two cell types dominate different fields of research, and a predominant use of hESCs as a “gold standard” in hiPSC research was not observed.

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          Most cited references27

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          Human induced pluripotent stem cells free of vector and transgene sequences.

          Reprogramming differentiated human cells to induced pluripotent stem (iPS) cells has applications in basic biology, drug development, and transplantation. Human iPS cell derivation previously required vectors that integrate into the genome, which can create mutations and limit the utility of the cells in both research and clinical applications. We describe the derivation of human iPS cells with the use of nonintegrating episomal vectors. After removal of the episome, iPS cells completely free of vector and transgene sequences are derived that are similar to human embryonic stem (ES) cells in proliferative and developmental potential. These results demonstrate that reprogramming human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors and removes one obstacle to the clinical application of human iPS cells.
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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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              Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells.

              Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to human embryonic stem cells (HESCs). Using two genetic lineage-tracing systems, we demonstrate the generation of iPSC lines from human pancreatic islet beta cells. These reprogrammed cells acquired markers of pluripotent cells and differentiated into the three embryonic germ layers. However, the beta cell-derived iPSCs (BiPSCs) maintained open chromatin structure at key beta-cell genes, together with a unique DNA methylation signature that distinguishes them from other PSCs. BiPSCs also demonstrated an increased ability to differentiate into insulin-producing cells both in vitro and in vivo, compared with ESCs and isogenic non-beta iPSCs. Our results suggest that the epigenetic memory may predispose BiPSCs to differentiate more readily into insulin producing cells. These findings demonstrate that HiPSC phenotype may be influenced by their cells of origin, and suggest that their skewed differentiation potential may be advantageous for cell replacement therapy. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Stem Cell Reports
                Stem Cell Reports
                Stem Cell Reports
                Elsevier
                2213-6711
                9 April 2015
                9 April 2015
                12 May 2015
                : 4
                : 5
                : 914-925
                Affiliations
                [1 ]Robert Koch Institute, D-13353 Berlin, Germany
                [2 ]Berlin-Brandenburg Center for Regenerative Therapies, D-13353 Berlin, Germany
                [3 ]Seoul National University, Seoul 151-742, Korea
                Author notes
                []Corresponding author andreas.kurtz@ 123456charite.de
                [∗∗ ]Corresponding author loeserp@ 123456rki.de
                [4]

                Co-first author

                Article
                S2213-6711(15)00096-X
                10.1016/j.stemcr.2015.03.002
                4437486
                25866160
                1c409457-3c3b-4311-8acb-f1b4288dfc5a
                © 2015 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 28 October 2014
                : 6 March 2015
                : 6 March 2015
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