Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate

Popp, Felix; Eggenhofer, Elke; Renner, Philipp; Slowik, Przemyslaw; Lang, Sven A.; Kaspar, Hannelore; Geissler, Edward K.; Piso, Pompiliu; Schlitt, Hans J.; Dahlke, Marc H.

doi:10.1016/j.trim.2008.08.004

Cited by 186 publications

(184 citation statements)

References 41 publications

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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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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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“…The effects of MSC administration on heart allograft survival are still unknown. Some authors have shown that in rats MSCs did not prolong allograft survival [60] and even accelerated allograft rejection when used alone [61] or when added to low-dose CSP [62], while other studies demonstrated increased heart allograft survival using MSCs alone [63][64][65][66] or when MSCs were added to MMF [60,67]. A combination of MSCs and low-dose sirolimus has enabled long-term heart graft survival of more than 100 days with normal histology [65].…”

Section: Animal Studiesmentioning

confidence: 99%

The use of mesenchymal stromal cells in solid organ transplantation

Delens

Jouret

Detry

et al. 2016

The Biology and Therapeutic Application of Mesenchymal Cells

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“…Inversely, it has been shown that MSCs are susceptible for lysis by NK cells (Spaggiari, Capobianco et al 2006;Crop, Korevaar et al 2011) as MSCs express the activating NK cell-receptor ligands NKG2D and UL16 (Poggi, Prevosto et al 2007). Moreover, intravenously administered MSCs have been demonstrated to disappear within days after infusion in immunocompetent mice (Popp, Eggenhofer et al 2008). It is possible that lysis by cytotoxic T cells (and not NK cells) is responsible for the disappearance of the infused MSCs (Eliopoulos, Stagg et al 2005).…”

Section: Natural Killer Cellsmentioning

confidence: 99%