A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection.
A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection.
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DOI：
10.1002/sctm.17-0134
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发表时间：
2017-12
影响因子：
6
通讯作者：
Wang FS
中科院分区：
文献类型：
--
作者：
Shi M;Liu Z;Wang Y;Xu R;Sun Y;Zhang M;Yu X;Wang H;Meng L;Su H;Jin L;Wang FS
尽管使用了现代免疫抑制剂，肝移植术后急性排斥反应仍然很常见。此外，这些方案的长期副作用，包括机会性感染，具有挑战性。本研究评价了脐带间充质干细胞（UC-MSC）治疗肝移植急性排斥反应患者的安全性和临床可行性。27例急性排斥反应的肝移植受者被随机分配到UC‐MSC输注组或对照组。13例患者接受了一次UC-MSC输注（1 × 106/kg体重）; 1例患者接受了多次UC-MSC输注; 13例患者用作对照。所有入组患者均接受常规免疫抑制剂，并在UC‐MSC输注后随访12周。治疗组未出现不良反应。在UC-MSC输注后4周，丙氨酸氨基转移酶水平显著降低，并在整个12周随访期间保持较低水平。重要的是，给予UC-MSC后，同种异体移植物组织学得到改善。输注后4周，调节性T细胞（TcR）的百分比和Treg/辅助性T细胞17（Th 17）的比例显著增加;相反，Th 17细胞的百分比呈下降趋势。在对照组中，Treg和Th 17细胞的百分比以及Treg/Th 17比率与基线测量相比在统计学上没有变化。UC-MSC输注后转化生长因子β 1和前列腺素E2显著增加;相比之下，对照组无显著变化。我们的数据表明，UC‐MSC输注治疗肝移植后的急性移植物排斥是可行的，并可能介导治疗性免疫抑制作用。干细胞转化医学2017;6：2053-2061
Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned into the UC‐MSC infusion group or the control group. Thirteen patients received one infusion of UC‐MSCs (1 × 106/kg body weight); one patient received multiple UC‐MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow‐up for 12 weeks after UC‐MSC infusions. No side effects occurred in treated patients. Four weeks after UC‐MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12‐week follow‐up period. Importantly, allograft histology was improved after administration of UC‐MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC‐MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC‐MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect. Stem Cells Translational Medicine 2017;6:2053–2061
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