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      Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine

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          Abstract

          Mesenchymal stem cells (MSCs), adherent fibroblastoid cells, present in bone marrow and many other tissues can be easily isolated and expanded in vitro. They are capable of differentiating into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells and neuronal cells. Such immense plasticity coupled with their ability to modulate the activity of immune cells makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. Preclinical studies have reported successful use of MSCs for delivering therapeutic proteins and repairing defects in a variety of disease models. These studies highlighted the in vivo potential of MSCs and their ability to home to injury sites and modify the microenvironment by secreting paracrine factors to augment tissue repair. Their therapeutic applicability has been widened by genetic modification to enhance differentiation and tissue targeting, and use in tissue engineering. Clinical trials for diseases such as osteogenesis imperfecta, graft-versus-host disease and myocardial infarction have shown some promise, demonstrating the safe use of both allogeneic and autologous cells. However, lack of knowledge of MSC behaviour and responses in vitro and i n vivo force the need for basic and animal studies before heading to the clinic. Contrasting reports on immunomodulatory functions and tumorigenicity along with issues such as mode of cell delivery, lack of specific marker, low survival and engraftment require urgent attention to harness the potential of MSC-based therapy in the near future.

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          Most cited references143

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          Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.

          Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.
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            Progress and problems with the use of viral vectors for gene therapy.

            Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.
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              Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views.

              Mesenchymal stem cells or multipotent stromal cells (MSCs) isolated from the bone marrow of adult organisms were initially characterized as plastic adherent, fibroblastoid cells with the capacity to generate heterotopic osseous tissue when transplanted in vivo. In recent years, MSCs or MSC-like cells have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well described. A large number of reports have also indicated that the cells possess the capacity to transdifferentiate into epithelial cells and lineages derived from the neuroectoderm. The broad developmental plasticity of MSCs was originally thought to contribute to their demonstrated efficacy in a wide variety of experimental animal models of disease as well as in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for transdifferentiation in tissue repair. Herein, we critically evaluate the literature describing the plasticity of MSCs and offer insight into how the molecular and functional heterogeneity of this cell population, which reflects the complexity of marrow stroma as an organ system, may confound interpretation of their transdifferentiation potential. Additionally, we argue that this heterogeneity also provides a basis for the broad therapeutic efficacy of MSCs.
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                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                jcmm
                Journal of Cellular and Molecular Medicine
                John Wiley & Sons, Ltd (Chichester, UK )
                1582-1838
                1582-4934
                Nov-Dec 2009
                10 July 2009
                : 13
                : 11-12
                : 4385-4402
                Affiliations
                [a ]Stem Cell and Gene Therapy Research Group, Institute of Nuclear Medicine and Allied Sciences Lucknow Road, Timarpur, Delhi, India
                [b ]Department of Biotechnology, Hamdard University Hamdard Nagar, New Delhi, India
                Author notes
                * Correspondence to: G. U. GURUDUTTA, Stem Cell and Gene Therapy Research Group, Institute of Nuclear Medicine and Allied Sciences, Lucknow Road, Timarpur, Delhi 110054, India. Tel.: 91-11-23905144 Fax: 91-11-25737049 E-mail: gugdutta@ 123456rediffmail.com
                Article
                10.1111/j.1582-4934.2009.00857.x
                4515054
                19602034
                2d7fb5a9-5bca-436e-a57d-efa0e951fb65
                © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
                History
                : 12 August 2008
                : 07 July 2009
                Categories
                Reviews

                Molecular medicine
                mesenchymal stem cells,stem cell therapy,genetic modification,protein therapy,tissue engineering

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