Transforming growth factor-β1-overexpressing mesenchymal stromal cells induced local tolerance in rat renal ischemia/reperfusion injury
Transforming growth factor-β1-overexpressing mesenchymal stromal cells induced local tolerance in rat renal ischemia/reperfusion injury
复制标题
转化生长因子-b1过表达间充质基质细胞诱导大鼠肾缺血/再灌注损伤的局部耐受
DOI：
10.1016/j.jcyt.2018.12.003
复制
发表时间：
2019-05-01
期刊：
影响因子：
4.5
通讯作者：
Yu, Xiaofang
中科院分区：
文献类型：
--
作者：
Cai, Jieru;Jiao, Xiaoyan;Yu, Xiaofang
背景：调节性T细胞（Treg）抑制过度的免疫反应，并在急性肾损伤（阿基）中发挥重要的保护作用。本研究的目的是研究转化生长因子（TGF）-β 1-过表达间充质基质细胞（MSCs）在诱导局部产生的Tcl 4在肾脏缺血/再灌注（I/R）损伤后的治疗潜力。研究方法：用表达TGF-β 1基因的慢病毒载体转导MSC;然后通过肾动脉将TGF-β 1过表达的MSC（称为TGF-β 1/MSC）输注到I/R损伤的肾脏中。结果：TGF-β 1基因修饰的MSCs表达TGF-β 1。与绿色荧光蛋白（GFP）/MSCs相比，TGF-β 1/MSCs明显改善了I/R损伤后的肾功能，减少了上皮细胞凋亡和随后的炎症反应。TGF-β 1/MSC增强的免疫抑制和治疗能力与诱导的TGF β 1的产生增加和注射细胞的肾内迁移改善相关。此外，TGF-β 1/MSC减轻肾I/R损伤的机制并非通过直接的经典TGF-β 1/Smad途径。结论：TGF-β 1/MSCs对I/R损伤的肾脏具有局部免疫抑制作用。TGF-β 1修饰的MSC的免疫调节活性似乎是预防肾I/R损伤的新治疗方法的门户。
Background: Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-beta 1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury. Methods: MSCs were transduced with a lentiviral vector expressing the TGF-beta 1 gene; TGF-beta 1-overexpressing MSCs (designated TGF-beta 1/MSCs) were then transfused into the I/R-injured kidney via the renal artery. Results: MSCs genetically modified with TGF-b1 achieved overexpression of TGF-beta 1. Compared with green fluorescent protein (GFP)/MSCs, TGF-beta 1/MSCs markedly improved renal function after I/R injury and reduced epithelial apoptosis and subsequent inflammation. The enhanced immunosuppressive and therapeutic abilities of TGF-beta 1/MSCs were associated with increased generation of induced Tregs and improved intrarenal migration of the injected cells. Futhermore, the mechanism of TGF-beta 1/MSCs in attenuating renal I/R injury was not through a direct canonical TGF-beta 1/Smad pathway. Conclusion: TGF-beta 1/MSCs can induce a local immunosuppressive effect in the I/R-injured kidney. The immunomodulatory activity of TGF-beta 1-modified MSCs appears to be a gateway to new therapeutic approaches to prevent renal I/R injury.