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      hiPSC‐derived iMSCs: NextGen MSCs as an advanced therapeutically active cell resource for regenerative medicine

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          Abstract

          Mesenchymal stem cells ( MSCs) are being assessed for ameliorating the severity of graft‐versus‐host disease, autoimmune conditions, musculoskeletal injuries and cardiovascular diseases. While most of these clinical therapeutic applications require substantial cell quantities, the number of MSCs that can be obtained initially from a single donor remains limited. The utility of MSCs derived from human‐induced pluripotent stem cells (hi PSCs) has been shown in recent pre‐clinical studies. Since adult MSCs have limited capability regarding proliferation, the quantum of bioactive factor secretion and immunomodulation ability may be constrained. Hence, the alternate source of MSCs is being considered to replace the commonly used adult tissue‐derived MSCs. The MSCs have been obtained from various adult and foetal tissues. The hi PSC‐derived MSCs ( iMSCs) are transpiring as an attractive source of MSCs because during reprogramming process, cells undergo rejuvination, exhibiting better cellular vitality such as survival, proliferation and differentiations potentials. The autologous iMSCs could be considered as an inexhaustible source of MSCs that could be used to meet the unmet clinical needs. Human‐induced PSC‐derived MSCs are reported to be superior when compared to the adult MSCs regarding cell proliferation, immunomodulation, cytokines profiles, microenvironment modulating exosomes and bioactive paracrine factors secretion. Strategies such as derivation and propagation of iMSCs in chemically defined culture conditions and use of footprint‐free safer reprogramming strategies have contributed towards the development of clinically relevant cell types. In this review, the role of i PSC‐derived mesenchymal stromal cells ( iMSCs) as an alternate source of therapeutically active MSCs has been described. Additionally, we also describe the role of iMSCs in regenerative medical applications, the necessary strategies, and the regulatory policies that have to be enforced to render iMSC's effectiveness in translational medicine.

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          Reprogramming of human somatic cells to pluripotency with defined factors.

          Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.
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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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              In search of the ‘missing self’: MHC molecules and NK cell recognition

              Immunology Today, 11, 237-244
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                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                21 April 2016
                August 2016
                : 20
                : 8 ( doiID: 10.1111/jcmm.2016.20.issue-8 )
                : 1571-1588
                Affiliations
                [ 1 ] Center for Stem Cell Research A Unit of inStem BengaluruChristian Medical College Vellore Tamil NaduIndia
                Author notes
                [*] [* ] Correspondence to: Sanjay KUMAR, Ph.D.

                E‐mail: skumar@ 123456cmcvellore.ac.in

                Article
                JCMM12839
                10.1111/jcmm.12839
                4956943
                27097531
                829a10c6-6802-4009-8414-ab78cc83fe67
                © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 January 2016
                : 14 February 2016
                Page count
                Pages: 18
                Funding
                Funded by: DBT
                Award ID: BT/PR8527/MED/31/234/2013
                Award ID: BT/PR8742/AGR/36/773/2013
                Award ID: BT/PR15420/MED/31/122/2011
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                jcmm12839
                August 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.2 mode:remove_FC converted:22.07.2016

                Molecular medicine
                mesenchymal stem cells,mscs,induced pluripotent stem cells,hipscs,imscs
                Molecular medicine
                mesenchymal stem cells, mscs, induced pluripotent stem cells, hipscs, imscs

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