Donor-Derived Mesenchymal Stem Cells Combined With Low-Dose Tacrolimus Prevent Acute Rejection After Renal Transplantation: A Clinical Pilot Study
Donor-Derived Mesenchymal Stem Cells Combined With Low-Dose Tacrolimus Prevent Acute Rejection After Renal Transplantation: A Clinical Pilot Study
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供体间充质干细胞联合低剂量他克莫司预防肾移植后急性排斥反应：一项临床试点研究
DOI：
10.1097/tp.0b013e3182754c53
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发表时间：
2013-01-15
期刊：
影响因子：
6.2
通讯作者：
Xiang, Andy Peng
中科院分区：
文献类型：
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作者：
Peng, Yanwen;Ke, Ming;Xiang, Andy Peng
背景钙调磷酸酶抑制剂的不良副作用损害了肾移植后的长期生存。需要新的免疫治疗方案，最大限度地减少或甚至消除钙调磷酸酶抑制剂，以改善移植结果。间充质干细胞（MSCs）是一种具有免疫抑制功能的独特细胞群，在实验性器官移植模型中可延长同种异体移植物的存活时间。在这项初步研究中，将供体来源的骨髓间充质干细胞与保留剂量的他克莫司（标准剂量的50%）联合给药于6名新生活体相关肾移植受者。另外六名接受标准剂量他克莫司的患者被纳入作为对照。观察两组间充质干细胞输注的安全性、急性排斥反应、移植肾功能、术后12个月内患者和移植肾存活情况。观察移植后不同时间点的免疫功能变化。没有MSC接受者经历与MSC输注相关的立即或长期毒副作用。与对照组（0.077 +/-0.005 mg/kg）相比，MSC组中他克莫司剂量（0.045 +/-0.002 mg/kg）显著降低。对照组仅发生1例急性排斥反应。所有患者均存活，第12个月肾功能稳定，第3个月未检测到嵌合体。骨髓间充质干细胞治疗组患者术后3个月B细胞水平明显高于对照组。这些初步数据表明，使用间充质干细胞可以通过减少维持长期移植物存活和功能所需的常规免疫抑制药物的剂量，在肾移植中提供潜在的益处。
Background. 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.Methods. 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.Results. 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.Conclusion. 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.