Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice

Xu, Dongli; Xiao, Yu; Zhang, D.; Zhang, M. X.; Zhou, Jianfeng; Tan, Peng; Ding, Yanping

doi:10.1007/s00125-011-2433-9

Cited by 36 publications

(19 citation statements)

References 33 publications

(50 reference statements)

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“…As for solid organ transplantation, Xu et al showed that the administration of MSCs significantly delays the rejection of allogeneic islet grafts in adaptive transferred recipients by favoring the induction of T-reg cells [25] and Tan showed that the clinical use of autologous MSCs compared with antiÀIL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection at 1 year among patients undergoing renal transplantation [26]. These results indirectly coincide with our findings and show clinical feasibility of MSCs infusion therapy for immunosuppression.…”

Section: Discussionmentioning

confidence: 98%

Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

Jeong

Yoon

2014

Transplantation Proceedings

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Section: Discussionmentioning

confidence: 98%

Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

Jeong

Yoon

2014

Transplantation Proceedings

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“…The immunosuppressive effect and low immunogenicity of mesenchymal stem cells (MSCs) make them ideal candidates for immunosuppressive strategies [3,4]. Adult MSCs have been used widely in the allogeneic heart [5][6][7][8][9][10][11], liver [12], islet [13][14][15][16][17], kidney [18,19], and composite tissue transplants [20,21]. Bone marrow mesenchymal stem cells (BM-MSCs) alone prolong heart allograft survival [8].…”

Section: Introductionmentioning

confidence: 99%

iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation

Cheng

Xiao-cun

et al. 2015

Stem Cells and Development

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Mesenchymal stem cell (MSC) differentiation is dramatically reduced after long-term in vitro culture, which limits their application. MSCs derived from induced pluripotent stem cells (iPSCs-MSCs) represent a novel source of MSCs. In this study, we investigated the therapeutic effect of iPSC-MSCs on diabetic mice. Streptozocin-induced diabetic mice transplanted with 400 islets alone or with 1 · 10 6 iPSC-MSCs were examined following rapamycin injection (0.1 mg/kg/day, i.p., from days 0 to 9) after transplantation. Our results showed that iPSC-MSCs combined with rapamycin significantly prolonged islet allograft survival in the diabetic mice; 50% of recipients exhibited long-term survival ( > 100 days). Histopathological analysis revealed that iPSCMSCs combined with rapamycin preserved the graft effectively, inhibited inflammatory cell infiltration, and resulted in substantial release of insulin. Flow cytometry results showed that the proportion of CD4 + and CD8 + T cells was significantly reduced, and the number of T regulatory cells increased in the spleen and lymph nodes in the iPSC-MSCs combined with the rapamycin group compared with the rapamycin-alone group. Production of the Th1 proinflammatory cytokines interleukin-2 (IL-2) and interferon-g was reduced, and secretion of the anti-inflammatory cytokines IL-10 and transforming growth factor-b was enhanced compared with the rapamycin group, as determined using enzyme-linked immunosorbent assays. Transwell separation significantly weakened the immunosuppressive effects of iPSC-MSCs on the proliferation of Con A-treated splenic T cells, which indicated that the combined treatment exerted immunosuppressive effects through cell-cell contact and regulation of cytokine production. Taken together, these findings highlight the potential application of iPSCMSCs in islet transplantation.

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“…However, some reports suggest that stem cells are unlikely to be used as a stand-alone therapy, because it may not be efficiently reverse autoimmunity of T1DM. They could be applied only for reducing immunosuppressant doses [88,89]. The timing of cell delivery, number of cells, engraftment, and cell manufacture are very important; however, there is still a lack of information in this regard [90].…”

Section: The Limitations Of Mesenchymal Stem Cell-based Therapy In DImentioning

confidence: 99%

Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes Mellitus

et al. 2015

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Diabetes mellitus type 1 is a form of diabetes mellitus that results from the autoimmune destruction of insulin-producing beta cells in the pancreas. The current gold standard therapy for pancreas transplantation has limitations because of the long list of waiting patients and the limited supply of donor pancreas. Mesenchymal stem cells (MSCs), a relatively new potential therapy in various fields, have already made their mark in the young field of regenerative medicine. Recent studies have shown that the implantation of MSCs decreases glucose levels through paracrine influences rather than through direct transdifferentiation into insulin-producing cells. Therefore, these cells may use pro-angiogenic and immunomodulatory effects to control diabetes following the cotransplantation with pancreatic islets. In this review, we present and discuss new approaches of using MSCs in the treatment of diabetes mellitus type 1.

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Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice

Cited by 36 publications

References 33 publications

Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation

Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes Mellitus

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