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      Current Strategies to Generate Human Mesenchymal Stem Cells In Vitro

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      Stem Cells International

      Hindawi

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          Abstract

          Mesenchymal stem cells (MSCs) are heterogeneous multipotent stem cells that are involved in the development of mesenchyme-derived evolving structures and organs during ontogeny. In the adult organism, reservoirs of MSCs can be found in almost all tissues where MSCs contribute to the maintenance of organ integrity. The use of these different MSCs for cell-based therapies has been extensively studied over the past years, which highlights the use of MSCs as a promising option for the treatment of various diseases including autoimmune and cardiovascular disorders. However, the proportion of MSCs contained in primary isolates of adult tissue biopsies is rather low and, thus, vigorous ex vivo expansion is needed especially for therapies that may require extensive and repetitive cell substitution. Therefore, more easily and accessible sources of MSCs are needed. This review summarizes the current knowledge of the different strategies to generate human MSCs in vitro as an alternative method for their applications in regenerative therapy.

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          Most cited references 78

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          Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation.

          Despite recent emerging evidence suggesting that cancer stem cells subsist in a variety of tumors, it is not yet fully elucidated whether postnatal stem cells are directly involved in tumorigenesis. We used murine bone marrow-derived mesenchymal stem cells (BMMSCs) as a model to test a hypothesis that tumorigenesis may originate from spontaneous mutation of stem cells. In this study, we demonstrated that murine BMMSCs, after numerous passages, obtained unlimited population doublings and proceeded to a malignant transformation state, resulting in fibrosarcoma formation in vivo. Transformed BMMSCs colonized to multiple organs when delivered systemically through the tail vein. Fibrosarcoma cells formed by transformed BMMSCs contained cancer progenitors, which were capable of generating colony clusters in vitro and fibrosarcoma in vivo by the second administration. The mechanism by which BMMSCs transformed to malignant cells was associated with accumulated chromosomal abnormalities, gradual elevation in telomerase activity, and increased c-myc expression. Moreover, BMMSCs and their transformed counterpart, fibrosarcoma-forming cells, demonstrated different sensitivity to anti-cancer drugs. BMMSCs/fibrosarcoma transformation system may provide an ideal system to elucidate the mechanism of how stem cells become cancer cells and to screen anti-sarcoma drugs.
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            Steps toward safe cell therapy using induced pluripotent stem cells.

            The enthusiasm for producing patient-specific human embryonic stem cells using somatic nuclear transfer has somewhat abated in recent years because of ethical, technical, and political concerns. However, the interest in generating induced pluripotent stem cells (iPSCs), in which pluripotency can be obtained by transcription factor transduction of various somatic cells, has rapidly increased. Human iPSCs are anticipated to open enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine and stem cell modeling of human disease. On the other hand, recent reports have emphasized the pitfalls of iPSC technology, including the potential for genetic and epigenetic abnormalities, tumorigenicity, and immunogenicity of transplanted cells. These constitute serious safety-related concerns for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. In this Review, recent achievements and future tasks for safe iPSC-based cell therapy are summarized, using regenerative medicine for repair strategies in the damaged central nervous system (CNS) as a model. Insights on safety and preclinical use of iPSCs in cardiovascular repair model are also discussed.
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              Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

              Mesenchymal stromal cells (MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC homing has been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.
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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                SCI
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2018
                26 August 2018
                : 2018
                Affiliations
                Institute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany
                Author notes

                Academic Editor: Stan Gronthos

                Article
                10.1155/2018/6726185
                6129345
                Copyright © 2018 Jennifer Steens and Diana Klein.

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

                Funding
                Funded by: Jürgen Manchot Stiftung
                Categories
                Review Article

                Molecular medicine

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