Immunomodulatory Effects of Mesenchymal Stem Cells in a Rat Organ Transplant Model

Inoue, Seiichiro; Popp, Felix; Koehl, Gudrun E.; Piso, Pompiliu; Schlitt, Hans J.; Geissler, Edward K.; Dahlke, Marc H.

doi:10.1097/01.tp.0000209919.90630.7b

Cited by 241 publications

(204 citation statements)

References 30 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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“…MSCs and cyclosporine A, a potent immunosuppressant, accelerated graft rejection in experimental GvHD instead of reinforcing MSC immunosuppression [65]. These data suggest that the setting of sustained inflammation, typical of several neonatal diseases, may represent an optimal environment for MSCs to exert their therapeutic effect.…”

Section: Inflammation and Mscs: Their Strength Grows Out Of Our Weaknmentioning

confidence: 80%

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

Pierro

Thébaud

2016

Curr Stem Cell Rep

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The imbalance of inflammatory and antiinflammatory responses in favor of inflammation plays a major role in the pathogenesis of many neonatal diseases. Inflammation in the perinatal period carries important longterm consequences, including neurodevelopmental and respiratory complications. Treatments able to restore immune homeostasis may reduce neonatal mortality and prevent longterm deleterious multi-organ consequences of unchecked inflammation. Mesenchymal stromal cells are a heterogenous group of progenitors cells with potent anti-inflammatory and immunomodulatory potential, among other diverse mechanisms of action. Thus, mesenchymal stromal cells (MSCs) may represent a novel and effective therapy for several neonatal diseases, potentially capable of preventing their longterm complications. This paper reviews the role of inflammation in the perinatal period and the therapeutic role of MSCs, focusing on their anti-inflammatory potential.

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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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Immunomodulatory Effects of Mesenchymal Stem Cells in a Rat Organ Transplant Model

Abstract: The present data confirm previous reports suggesting that MSCs have immunomodulatory properties in vitro. However, their tolerogenic properties in vivo must be questioned, as MSC injections were not only ineffective at prolonging allograft survival, but tended to promote rejection.

Cited by 241 publications

References 30 publications

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

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

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

The use of mesenchymal stromal cells in solid organ transplantation

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