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      Mesenchymal stem cells: a new trend for cell therapy

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          Abstract

          Mesenchymal stem cells (MSCs), the major stem cells for cell therapy, have been used in the clinic for approximately 10 years. From animal models to clinical trials, MSCs have afforded promise in the treatment of numerous diseases, mainly tissue injury and immune disorders. In this review, we summarize the recent opinions on methods, timing and cell sources for MSC administration in clinical applications, and provide an overview of mechanisms that are significant in MSC-mediated therapies. Although MSCs for cell therapy have been shown to be safe and effective, there are still challenges that need to be tackled before their wide application in the clinic.

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

          Katarina Le Blanc, Ida Rasmusson, Berit Sundberg … (2004)
          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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            Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone.

            E Horwitz, P L Gordon, W. K. K. Koo … (2002)
            Treatment with isolated allogeneic mesenchymal cells has the potential to enhance the therapeutic effects of conventional bone marrow transplantation in patients with genetic disorders affecting mesenchymal tissues, including bone, cartilage, and muscle. To demonstrate the feasibility of mesenchymal cell therapy and to gain insight into the transplant biology of these cells, we used gene-marked, donor marrow-derived mesenchymal cells to treat six children who had undergone standard bone marrow transplantation for severe osteogenesis imperfecta. Each child received two infusions of the allogeneic cells. Five of six patients showed engraftment in one or more sites, including bone, skin, and marrow stroma, and had an acceleration of growth velocity during the first 6 mo postinfusion. This improvement ranged from 60% to 94% (median, 70%) of the predicted median values for age- and sex-matched unaffected children, compared with 0% to 40% (median, 20%) over the 6 mo immediately preceding the infusions. There was no clinically significant toxicity except for an urticarial rash in one patient just after the second infusion. Failure to detect engraftment of cells expressing the neomycin phosphotransferase marker gene suggested the potential for immune attack against therapeutic cells expressing a foreign protein. Thus, allogeneic mesenchymal cells offer feasible posttransplantation therapy for osteogenesis imperfecta and likely other disorders originating in mesenchymal precursors.
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              Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms.

              Florian Tögel, Zhuma Hu, Kathleen A. Weiss … (2005)
              Severe acute renal failure (ARF) remains a common, largely treatment-resistant clinical problem with disturbingly high mortality rates. Therefore, we tested whether administration of multipotent mesenchymal stem cells (MSC) to anesthetized rats with ischemia-reperfusion-induced ARF (40-min bilateral renal pedicle clamping) could improve the outcome through amelioration of inflammatory, vascular, and apoptotic/necrotic manifestations of ischemic kidney injury. Accordingly, intracarotid administration of MSC (approximately 10(6)/animal) either immediately or 24 h after renal ischemia resulted in significantly improved renal function, higher proliferative and lower apoptotic indexes, as well as lower renal injury and unchanged leukocyte infiltration scores. Such renoprotection was not obtained with syngeneic fibroblasts. Using in vivo two-photon laser confocal microscopy, fluorescence-labeled MSC were detected early after injection in glomeruli, and low numbers attached at microvasculature sites. However, within 3 days of administration, none of the administered MSC had differentiated into a tubular or endothelial cell phenotype. At 24 h after injury, expression of proinflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma, and inducible nitric oxide synthase was significantly reduced and that of anti-inflammatory IL-10 and bFGF, TGF-alpha, and Bcl-2 was highly upregulated in treated kidneys. We conclude that the early, highly significant renoprotection obtained with MSC is of considerable therapeutic promise for the cell-based management of clinical ARF. The beneficial effects of MSC are primarily mediated via complex paracrine actions and not by their differentiation into target cells, which, as such, appears to be a more protracted response that may become important in late-stage organ repair.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Acta Pharmacol Sin
                Journal ID (iso-abbrev): Acta Pharmacol. Sin
                Title: Acta Pharmacologica Sinica
                Publisher: Nature Publishing Group
                ISSN (Print): 1671-4083
                ISSN (Electronic): 1745-7254
                Publication date (Print): June 2013
                Publication date (Electronic): 05 June 2013
                Volume: 34
                Issue: 6
                Pages: 747-754
                Affiliations
                [1 ]Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200127, China
                [2 ]Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine , Shanghai 200025, China
                [3 ]Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University , Shanghai 200433, China
                Author notes
                Article
                Publisher Item ID: aps201350
                DOI: 10.1038/aps.2013.50
                PMC ID: 4002895
                PubMed ID: 23736003
                SO-VID: b7f91bc6-1088-4cda-86a0-b0d3648457be
                Copyright © Copyright © 2013 CPS and SIMM
                History
                Date received : 11 March 2013
                Date accepted : 05 April 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: mesenchymal stem cell,cell therapy,tissue injury,degenerative disease,immune disorder,graft-versus-host disease,immunomodulation,trophic factor
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: mesenchymal stem cell, cell therapy, tissue injury, degenerative disease, immune disorder, graft-versus-host disease, immunomodulation, trophic factor

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