Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study

The deleterious side effects of calcineurin inhibitors have impaired long-term survival after renal allograft. New immunotherapy regimens that minimize or even eliminate calcineurin inhibitors are required to improve transplantation outcome. Mesenchymal stem cells (MSCs) represent a unique cell popu...

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Veröffentlicht in:Transplantation 2013-01, Vol.95 (1), p.161-168
Hauptverfasser: Peng, Yanwen, Ke, Ming, Xu, Lu, Liu, Longshan, Chen, Xiaoyong, Xia, Wenjie, Li, Xiaobo, Chen, Zhen, Ma, Junjie, Liao, Dehuai, Li, Guanghui, Fang, Jiali, Pan, Guanghui, Xiang, Andy Peng
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container_end_page 168
container_issue 1
container_start_page 161
container_title Transplantation
container_volume 95
creator Peng, Yanwen
Ke, Ming
Xu, Lu
Liu, Longshan
Chen, Xiaoyong
Xia, Wenjie
Li, Xiaobo
Chen, Zhen
Ma, Junjie
Liao, Dehuai
Li, Guanghui
Fang, Jiali
Pan, Guanghui
Xiang, Andy Peng
description The deleterious side effects of calcineurin inhibitors have impaired long-term survival after renal allograft. New immunotherapy regimens that minimize or even eliminate calcineurin inhibitors are required to improve transplantation outcome. Mesenchymal stem cells (MSCs) represent a unique cell population with immunosuppressive function and prolong allograft survival in experimental organ transplant models. In this pilot study, donor-derived bone marrow MSCs combined with a sparing dose of tacrolimus (50% of standard dose) were administered to six de novo living-related kidney transplant recipients. Six other patients who received a standard dose of tacrolimus were enrolled as a control. The safety of MSC infusion, acute rejection, graft function, and patient and graft survival within 12 months after kidney transplantation were observed. The immune profiles were analyzed at different time points after transplantation. None of the MSC recipients experienced immediate or long-term toxic side effects associated with MSC infusion. The tacrolimus dose (0.045±0.002 mg/kg) in the MSC group was significantly reduced compared with the control group (0.077±0.005 mg/kg). One acute rejection occurred only in the control group. All patients survived with stable renal function at month 12 and no chimerism was detectable at month 3. Patients in the MSC group showed significantly higher B-cell levels than the control group at month 3. 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.
doi_str_mv 10.1097/TP.0b013e3182754c53
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New immunotherapy regimens that minimize or even eliminate calcineurin inhibitors are required to improve transplantation outcome. Mesenchymal stem cells (MSCs) represent a unique cell population with immunosuppressive function and prolong allograft survival in experimental organ transplant models. In this pilot study, donor-derived bone marrow MSCs combined with a sparing dose of tacrolimus (50% of standard dose) were administered to six de novo living-related kidney transplant recipients. Six other patients who received a standard dose of tacrolimus were enrolled as a control. The safety of MSC infusion, acute rejection, graft function, and patient and graft survival within 12 months after kidney transplantation were observed. The immune profiles were analyzed at different time points after transplantation. None of the MSC recipients experienced immediate or long-term toxic side effects associated with MSC infusion. 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subjects Acute Disease
Adult
Bone marrow transplantation
Cytokines - analysis
Female
Graft Rejection - prevention & control
Humans
Immunosuppressive Agents - administration & dosage
Kidney Transplantation - adverse effects
Lymphocyte Culture Test, Mixed
Male
Mesenchymal Stem Cell Transplantation
Middle Aged
Pilot Projects
Tacrolimus - administration & dosage
Tissue Donors
Tumor Necrosis Factor Receptor Superfamily, Member 7 - analysis
title Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study
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