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      Immunomodulatory properties of stem cells from human exfoliated deciduous teeth

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          Abstract

          Introduction

          Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a population of postnatal stem cells capable of differentiating into osteogenic and odontogenic cells, adipogenic cells, and neural cells. Herein we have characterized mesenchymal stem cell properties of SHED in comparison to human bone marrow mesenchymal stem cells (BMMSCs).

          Methods

          We used in vitro stem cell analysis approaches, including flow cytometry, inductive differentiation, telomerase activity, and Western blot analysis to assess multipotent differentiation of SHED and in vivo implantation to assess tissue regeneration of SHED. In addition, we utilized systemic SHED transplantation to treat systemic lupus erythematosus (SLE)-like MRL/ lpr mice.

          Results

          We found that SHED are capable of differentiating into osteogenic and adipogenic cells, expressing mesenchymal surface molecules (STRO-1, CD146, SSEA4, CD73, CD105, and CD166), and activating multiple signaling pathways, including TGFβ, ERK, Akt, Wnt, and PDGF. Recently, BMMSCs were shown to possess an immunomodulatory function that leads to successful therapies for immune diseases. We examined the immunomodulatory properties of SHED in comparison to BMMSCs and found that SHED had significant effects on inhibiting T helper 17 (Th17) cells in vitro. Moreover, we found that SHED transplantation is capable of effectively reversing SLE-associated disorders in MRL/ lpr mice. At the cellular level, SHED transplantation elevated the ratio of regulatory T cells (Tregs) via Th17 cells.

          Conclusions

          These data suggest that SHED are an accessible and feasible mesenchymal stem cell source for treating immune disorders like SLE.

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          Most cited references25

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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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              Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo.

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                Author and article information

                Journal
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central
                1757-6512
                2010
                15 March 2010
                : 1
                : 1
                : 5
                Affiliations
                [1 ]Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA
                [2 ]Department of Oral Anatomy and Cell Biology, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan
                [3 ]Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 661 Hoes Lane, Piscataway, NJ 08854, USA
                [4 ]Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science/Hanson Institute/CSCR, University of Adelaide, Frome Rd, Adelaide, SA 5000, Australia
                [5 ]Salivary Gland Disease Center and the Molecular Laboratory for Gene Therapy & Tooth Regeneration, Capital Medical University School of Stomatology, Tian Tan Xi Li No.4, Beijing 100050, PR China
                Article
                scrt5
                10.1186/scrt5
                2873699
                20504286
                1057724f-6fc8-4f0a-b5c8-b31eb1ec4f23
                Copyright ©2010 Yamaza et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 July 2009
                : 15 March 2010
                Categories
                Research

                Molecular medicine
                Molecular medicine

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