Autologous Bone Marrow-Derived Mesenchymal Stromal Cells for the Treatment of Allograft Rejection After Renal Transplantation: Results of a Phase I Study
Autologous Bone Marrow-Derived Mesenchymal Stromal Cells for the Treatment of Allograft Rejection After Renal Transplantation: Results of a Phase I Study
复制标题
DOI：
10.5966/sctm.2012-0114
复制
发表时间：
2013-02-01
影响因子：
6
通讯作者：
Rabelink, Ton J.
中科院分区：
文献类型：
--
作者：
Reinders, Marlies E. J.;de Fijter, Johan W.;Rabelink, Ton J.
尽管短期效果很好，但移植肾的长期存活率并没有相应提高。尽管同种免疫反应和钙调磷酸酶相关的肾毒性已被确定为纤维化的主要驱动因素，但尚未出现有效的治疗选择。从这个角度来看，间充质基质细胞（MSC）是一个有趣的候选人，因为它们的免疫抑制和再生特性。重要的是，没有其他临床研究研究过它们对同种异体移植排斥反应和纤维化的影响。我们在肾同种异体移植受者中进行了安全性和可行性研究，当4周或6个月的方案肾活检显示排斥反应和/或间质纤维化/肾小管萎缩（IF/TA）增加时，给予两次静脉输注（每公斤100万个细胞）自体骨髓（BM）MSC。6例患者接受了MSC输注。在MSC输注后24周进行临床和免疫监测。MSC符合释放标准，输注耐受性良好，未报告治疗相关的严重不良事件。在两例同种异体移植排斥反应的受者中，我们有临床指征进行监测活检，并能够报告骨髓间充质干细胞在排斥反应中的潜在作用。虽然维持免疫抑制保持不变，有一个决议的小管炎没有IF/TA在这两个病人。此外，3名患者发生机会性病毒感染，6名患者中有5名显示外周血单核细胞增殖测定的供体特异性下调，未在未接受MSC治疗的患者中报告。自体骨髓间充质干细胞治疗亚临床排斥反应和IF/TA的移植受者在临床上是可行和安全的，研究结果提示全身免疫抑制。干细胞翻译医学2013;2：107-111
Despite excellent short-term results, long-term survival of transplanted kidneys has not improved accordingly. Although alloimmune responses and calcineurin inhibitor-related nephrotoxicity have been identified as main drivers of fibrosis, no effective treatment options have emerged. In this perspective, mesenchymal stromal cells (MSCs) are an interesting candidate because of their immunosuppressive and regenerative properties. Of importance, no other clinical studies have investigated their effects in allograft rejection and fibrosis. We performed a safety and feasibility study in kidney allograft recipients to whom two intravenous infusions (1 million cells per kilogram) of autologous bone marrow (BM) MSCs were given, when a protocol renal biopsy at 4 weeks or 6 months showed signs of rejection and/or an increase in interstitial fibrosis/tubular atrophy (IF/TA). Six patients received MSC infusions. Clinical and immune monitoring was performed up to 24 weeks after MSC infusions. MSCs fulfilled the release criteria, infusions were well-tolerated, and no treatment-related serious adverse events were reported. In two recipients with allograft rejection, we had a clinical indication to perform surveillance biopsies and are able to report on the potential effects of MSCs in rejection. Although maintenance immunosuppression remained unaltered, there was a resolution of tubulitis without IF/TA in both patients. Additionally, three patients developed an opportunistic viral infection, and five of the six patients displayed a donor-specific downregulation of the peripheral blood mononuclear cell proliferation assay, not reported in patients without MSC treatment. Autologous BM MSC treatment in transplant recipients with subclinical rejection and IF/TA is clinically feasible and safe, and the findings are suggestive of systemic immunosuppression. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:107-111