Donor-Derived Mesenchymal Stem Cells Combined With Low-Dose Tacrolimus Prevent Acute Rejection After Renal Transplantation

Peng, Yanwen; Ke, Ming; Xu, Lu; Liu, Longshan; Xia, Wenjie; Li, Xiaobo; Chen, Zhen; Ma, Junjie; Liao, Dehuai; Li, Guanghui; Fang, Jiali; Pan, Guangdong; Xiang, Andy Peng

doi:10.1097/tp.0b013e3182754c53

Cited by 152 publications

(126 citation statements)

References 32 publications

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“…Furthermore, MSCs combined with cyclosporine A (CsA) induced tolerance of islet allografts in immune-deficient mice [14]. In a kidney allograft model, MSCs led to long-term graft acceptance in rodents [19] and had immunosuppressive effects in renal transplant recipients [22][23][24], which suggested that MSCs may reduce immunosuppressant dosage [25,26]. Collectively, these studies suggested that under certain conditions, MSCs could prolong allograft survival in combination with clinical immunosuppressants.…”

Section: Introductionmentioning

confidence: 88%

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: 88%

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 authors of this study concluded that autologous mesenchymal stem cell injection results in a lower incidence of acute rejection, a decreased risk of opportunistic infection and better regulated renal function at 1 year. Thus, although these studies differ in many aspects, such as the type of mesenchymal stem cells, their allogeneic or autologous status, their time and site of injection and protocols of immunosuppressive therapy, all of them suggest that stem cell injection is a safe strategy [90][91][92][93][94]. However, these studies were performed in LD kidneys, and not in those obtained through DBD or DCD, which are more sensitive to ischemia-reperfusion sequence.…”

Section: Strategies To Limit Renal Ischemia-reperfusion Injuries Andmentioning

confidence: 99%

Strategies to optimize kidney recovery and preservation in transplantation: specific aspects in pediatric transplantation

et al. 2014

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In renal transplantation, live donor kidney grafts are associated with optimum success rates due to the shorter period of ischemia during the surgical procedure. The current shortage of donor organs for adult patients has caused a shift towards deceased donors, often with co-morbidity factors, whose organs are more sensitive to ischemia-reperfusion injury, which is unavoidable during transplantation. Donor management is pivotal to kidney graft survival through the control of the ischemiareperfusion sequence, which is known to stimulate numerous deleterious or regenerative pathways. Although the key role of endothelial cells has been established, the complexity of the injury, associated with stimulation of different cell signaling pathways, such as unfolded protein response and cell death, prevents the definition of a unique therapeutic target. Preclinical transplant models in large animals are necessary to establish relationships and kinetics and have already contributed to the improvement of organ preservation. Therapeutic strategies using mesenchymal stem cells to induce allograft tolerance are promising advances in the treatment of the pediatric recipient in terms of reducing/withdrawing immunosuppressive therapy. In this review we focus on the different donor management strategies in kidney graft conditioning and on graft preservation consequences by highlighting the role of endothelial cells. We also propose strategies for preventing ischemia-reperfusion, such as cell therapy.

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“…The results of this showed no toxic adverse effects associated with MSC infusion and all patients survived with stable graft function to 12 mo with only 1 acute rejection episode in the control group. The one difference they did notice was elevated B-cell counts in the MSC group at 3 mo compared to the control [58] . They concluded that MSCs may provide benefits in renal transplantation by reducing the required dose of conventional immunosuppressive drug that is required for long term graft survival.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

“…They concluded that pre-transplant administration of MSCs avoided the cell induced graft dysfunction associated with posttransplant MSC administration and that this method is favourable for future trials. Peng et al [58] examined the effect of autologous MSCs on renal transplants by giving 6 patients MSCs combined with half doses of tacrolimus and comparing acute rejection, graft function, and graft survival at 12 mo to a control group of 6 patients receiving standard dose tacrolimus. The results of this showed no toxic adverse effects associated with MSC infusion and all patients survived with stable graft function to 12 mo with only 1 acute rejection episode in the control group.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Mesenchymal stem cells for kidney transplantation

Lett¹,

Sivanathan²,

Coates³

2014

WJCU

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The long term consequence of immunosuppressive therapy in kidney transplantation has prompted investigation of alternative means to modify the immune response to the allograft. Cell based therapies are potentially attractive as they may provide a long lasting immunomodulatory effect, may repair tissues and reduce the necessity to take immunosuppressive drug therapy. Of the current cell therapies, mesenchymal stem cells have now been trialled in small numbers of human kidney transplantation with apparent safety and potential efficacy. Many issues however need to be resolved before these cells will become mainstays of transplant immunosuppression including ex vivo modification to enhance immunomodulatory properties, cell number, route and frequency of administration as well as cellular source of origin.

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Donor-Derived Mesenchymal Stem Cells Combined With Low-Dose Tacrolimus Prevent Acute Rejection After Renal Transplantation

Abstract: These preliminary data suggest that the use of MSCs could provide potential benefits in renal transplantation by reducing the dosage of conventional immunosuppressive drug that is required to maintain long-term graft survival and function.

Cited by 152 publications

References 32 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

Strategies to optimize kidney recovery and preservation in transplantation: specific aspects in pediatric transplantation

Mesenchymal stem cells for kidney transplantation

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