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      Advances in regenerative therapy: A review of the literature and future directions

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          Abstract

          There is enormous global anticipation for stem cell-based therapies that are safe and effective. Numerous pre-clinical studies present encouraging results on the therapeutic potential of different cell types including tissue derived stem cells. Emerging evidences in different fields of research suggest several cell types are safe, whereas their therapeutic application and effectiveness remain challenged. Multiple factors that influence treatment outcomes are proposed including immunocompatibility and potency, owing to variations in tissue origin, ex-vivo methodologies for preparation and handling of the cells. This communication gives an overview of literature data on the different types of cells that are potentially promising for regenerative therapy. As a case in point, the recent trends in research and development of the mesenchymal stem cells (MSCs) for cell therapy are considered in detail. MSCs can be isolated from a variety of tissues and organs in the human body including bone marrow, adipose, synovium, and perinatal tissues. However, MSC products from the different tissue sources exhibit unique or varied levels of regenerative abilities. The review finally focuses on adipose tissue-derived MSCs (ASCs), with the unique properties such as easier accessibility and abundance, excellent proliferation and differentiation capacities, low immunogenicity, immunomodulatory and many other trophic properties. The suitability and application of the ASCs, and strategies to improve the innate regenerative capacities of stem cells in general are highlighted among others.

          Highlights

          • The current successes and challenges of cell-based therapies.

          • Basic strategies to enhance the innate potential in stem cells for therapy.

          • Experiences of applying ex vivo culture expanded stem cells in aesthetic surgery.

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          Most cited references192

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          Concise review: the surface markers and identity of human mesenchymal stem cells.

          The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments. Markers that associate with the stemness of MSCs await to be elucidated. A number of candidate MSC surface markers or markers possibly related to their stemness have been brought forward so far, including Stro-1, SSEA-4, CD271, and CD146, yet there is a large difference in their expression in various sources of MSCs. The exact identity of MSCs in vivo is not yet clear, although reports have suggested they may have a fibroblastic or pericytic origin. In this review, we revisit the reported expression of surface molecules in MSCs from various sources, aiming to assess their potential as MSC markers and define the critical panel for future investigation. We also discuss the relationship of MSCs to fibroblasts and pericytes in an attempt to shed light on their identity in vivo. © 2014 AlphaMed Press.
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            In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

            SUMMARY The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here, we use genetic lineage-tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became bi-nucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast activating peptide, Thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes.
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              Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord.

              The Wharton's jelly of the umbilical cord contains mucoid connective tissue and fibroblast-like cells. Using flow cytometric analysis, we found that mesenchymal cells isolated from the umbilical cord express matrix receptors (CD44, CD105) and integrin markers (CD29, CD51) but not hematopoietic lineage markers (CD34, CD45). Interestingly, these cells also express significant amounts of mesenchymal stem cell markers (SH2, SH3). We therefore investigated the potential of these cells to differentiate into cardiomyocytes by treating them with 5-azacytidine or by culturing them in cardiomyocyte-conditioned medium and found that both sets of conditions resulted in the expression of cardiomyocyte markers, namely N-cadherin and cardiac troponin I. We also showed that these cells have multilineage potential and that, under suitable culture conditions, are able to differentiate into cells of the adipogenic and osteogenic lineages. These findings may have a significant impact on studies of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering by helping to eliminate worrying ethical and technical issues.
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                Author and article information

                Contributors
                Journal
                Regen Ther
                Regen Ther
                Regenerative Therapy
                Japanese Society for Regenerative Medicine
                2352-3204
                20 February 2020
                June 2020
                20 February 2020
                : 14
                : 136-153
                Affiliations
                [a ]Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Japan
                [b ]Research Center for Regenerative Medicine, School of Medicine, University of the Ryukyus, Japan
                Author notes
                []Corresponding author. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa 903-0215, Japan. yyssprs@ 123456gmail.com
                Article
                S2352-3204(20)30004-3
                10.1016/j.reth.2020.01.004
                7033303
                32110683
                105b926d-d7a4-4ec4-aeff-1fe8b60fd9fb
                © 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 11 November 2019
                : 14 January 2020
                : 26 January 2020
                Categories
                Review Article

                regenerative therapies,tissue engineering,tissue derived stem cells,mesenchymal stem cells,adipose-derived stem cells,ex vivo culture-expanded stem cells,scaffold free-cellsheet technology,scaffold-based cellsheet technology

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