Autologous Mesenchymal Stromal Cells and Kidney Transplantation: A Pilot Study of Safety and Clinical Feasibility
Autologous Mesenchymal Stromal Cells and Kidney Transplantation: A Pilot Study of Safety and Clinical Feasibility
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DOI：
10.2215/cjn.04950610
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发表时间：
2011-02-01
影响因子：
9.8
通讯作者：
Remuzzi, Giuseppe
中科院分区：
文献类型：
--
作者：
Perico, Norberto;Casiraghi, Federica;Remuzzi, Giuseppe
背景与目的骨髓间充质干细胞（MSCs）在体外可消除同种异体免疫反应，为移植提供了一种新的细胞基础方法。将这一概念向器官移植的临床应用转移应该进行严格的评估。设计、设置、参与者和测量在两名来自活体亲属供体的肾脏接受者中进行自体MSC输注的安全性和临床可行性研究（ClinicalTrials.gov，NCT 00752479）。患者接受T细胞耗竭诱导治疗，并使用环孢素和霉酚酸酯维持免疫抑制。在移植后第7天，静脉内施用MSC。MSC治疗的患者的临床和免疫监测进行了360天postsurgical.Results血肌酐水平上升7至14天后，在两个MSC治疗的患者细胞输注。患者2的移植物活检排除了急性移植物排斥反应，但显示局灶性炎症浸润，主要是粒细胞。在患者1中，移植后1年的方案活检显示移植物正常。两名MSC治疗的患者健康状况良好，移植物功能稳定。移植后CD 4（+）CD 25（高）FoxP 3（+）CD 127（-）Treg百分比逐渐升高，记忆性CD 45 RO（+）RA（-）CD 8（+）T细胞扩增明显抑制。患者T细胞显示出CD 8（+）T细胞活性的显著降低。结论两例患者的研究结果表明，肾移植受者的MSC输注是可行的，可以扩大外周血中的Treg，并控制记忆性CD 8（+）T细胞功能。建议将来使用MSC进行临床试验，以最大限度地关注不必要的副作用。Clin J Am Soc Nephrol 6：412-422，2011. doi：10.2215/CJN.04950610
Background and objectives Mesenchymal stromal cells (MSCs) abrogate alloimmune response in vitro, suggesting a novel cell-based approach in transplantation. Moving this concept toward clinical application in organ transplantation should be critically assessed.Design, setting, participants & measurements A safety and clinical feasibility study (ClinicalTrials.gov, NCT00752479) of autologous MSC infusion was conducted in two recipients of kidneys from living-related donors. Patients were given T cell-depleting induction therapy and maintenance immunosuppression with cyclosporine and mycophenolate mofetil. On day 7 posttransplant, MSCs were administered intravenously. Clinical and immunomonitoring of MSC-treated patients was performed up to day 360 postsurgery.Results Serum creatinine levels increased 7 to 14 days after cell infusion in both MSC-treated patients. A graft biopsy in patient 2 excluded acute graft rejection, but showed a focal inflammatory infiltrate, mostly granulocytes. In patient 1 protocol biopsy at 1-year posttransplant showed a normal graft. Both MSC-treated patients are in good health with stable graft function. A progressive increase of the percentage of CD4(+)CD25(high)FoxP3(+)CD127(-) Treg and a marked inhibition of memory CD45RO(+)RA(-)CD8(+) T cell expansion were observed posttransplant. Patient T cells showed a profound reduction of CD8(+) T cell activity.Conclusions Findings from this study in the two patients show that MSC infusion in kidney transplant recipients is feasible, allows enlargement of Treg in the peripheral blood, and controls memory CD8(+) T cell function. Future clinical trials with MSCs to look with the greatest care for unwanted side effects is advised. Clin J Am Soc Nephrol 6: 412-422, 2011. doi: 10.2215/CJN.04950610