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      Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials

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          Abstract

          Human mesenchymal stem cells (MSCs) are multilineage somatic progenitor/stem cells that have been shown to possess immunomodulatory properties in recent years. Initially met with much skepticism, MSC immunomodulation has now been well reproduced across tissue sources and species to be clinically relevant. This has opened up the use of these versatile cells for application as 3rd party/allogeneic use in cell replacement/tissue regeneration, as well as for immune- and inflammation-mediated disease entities. Most surprisingly, use of MSCs for in immune-/inflammation-mediated diseases appears to yield more efficacy than for regenerative medicine, since engraftment of the exogenous cell does not appear necessary. In this review, we focus on this non-traditional clinical use of a tissue-specific stem cell, and highlight important findings and trends in this exciting area of stem cell therapy.

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          Inflammatory bowel disease.

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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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              Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.

              Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various components of the marrow microenvironment, such as bone, adipose, and stromal tissues. The bone marrow microenvironment is vital to the development, differentiation, and regulation of the lymphohematopoietic system. We hypothesized that the activities of MSCs in the bone marrow microenvironment might also include immunomodulatory effects on lymphocytes. Baboon MSCs were tested in vitro for their ability to elicit a proliferative response from allogeneic lymphocytes, to inhibit an ongoing allogeneic response, and to inhibit a proliferative response to potent T-cell mitogens. In vivo effects were tested by intravenous administration of donor MSCs to MHC-mismatched recipient baboons prior to placement of autologous, donor, and third-party skin grafts. MSCs failed to elicit a proliferative response from allogeneic lymphocytes. MSCs added into a mixed lymphocyte reaction, either on day 0 or on day 3, or to mitogen-stimulated lymphocytes, led to a greater than 50% reduction in proliferative activity. This effect could be maximized by escalating the dose of MSCs and could be reduced with the addition of exogenous IL-2. In vivo administration of MSCs led to prolonged skin graft survival when compared to control animals: 11.3 +/- 0.3 vs 7 +/- 0. Baboon MSCs have been observed to alter lymphocyte reactivity to allogeneic target cells and tissues. These immunoregulatory features may prove useful in future applications of tissue regeneration and stem cell engineering.
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                Author and article information

                Contributors
                +037-246-166 , blyen@nhri.org.tw
                Journal
                J Biomed Sci
                J. Biomed. Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                4 November 2016
                4 November 2016
                2016
                : 23
                Affiliations
                [1 ]Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), 35 Keyan Road, Zhunan, 35053 Taiwan
                [2 ]Graduate Institute of Life Sciences, National Defense Medical Center (NDMC), Taipei, Taiwan
                [3 ]Department of Ob/Gyn, National Taiwan University Hospital & College of Medicine, National Taiwan University, Taipei, Taiwan
                [4 ]National Institute of Cancer Research, NHRI, Tainan, Taiwan
                [5 ]Graduate Institute of Microbiology and Immunology, NDMC, Taipei, Taiwan
                [6 ]Graduate Institute of Basic Medical Sciences, China Medical College, Taichung, Taiwan
                Article
                289
                10.1186/s12929-016-0289-5
                5095977
                27809910
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: MOST-104-2321-B-400-021
                Award ID: MOST-104-2314-B-400-002
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004737, National Health Research Institutes;
                Award ID: CS-105-PP-06
                Award Recipient :
                Categories
                Review
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                © The Author(s) 2016

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