Qian Hui, Yang Huan, Xu Wenrong, Yan Yongmin, Chen Qiaolin, Zhu Wei, Cao Huiling, Yin Qin, Zhou Hongxing, Mao Fei, Chen Yongchang
Zhenjiang Key Institute of Clinical Laboratory Medicine, School of Medical Technology, Jiangsu University, Zhenjiang 212013, P.R. China.
Int J Mol Med. 2008 Sep;22(3):325-32.
In the present study, we investigated the therapeutic potential of mesenchymal stem cells (MSCs) in a rat acute renal failure (ARF) model and explored the possible in vivo and in vitro mechanisms of action. Rat and human MSCs were isolated from bone marrow. After being co-cultured with injured kidney tissues in trans-well dishes in vitro, the rat MSCs became rounded renal tubular epithelial-like cells, and highly expressed renal markers such as cytokeratin 18 (CK18) and aquaporin-1 (AQP1). Human MSCs were infused into rats with ARF, and techniques of microscopy, histology, PCR, RT-PCR and fluorescence in situ hybridization were used to characterize the MSCs after transplantation. We found that there were more exogenous human MSCs localized to injured kidney tissues. The kidney recovery rate in the transplanted MSC group was higher than in the control group. Genes associated with human renal tubular epithelial cells such as AQP1 and parathyroid hormone receptor 1 were detected. These findings suggest that the injured kidney tissue induced rat and human MSCs to differentiate into renal tubular epithelial-like cells in vitro and in vivo, and exogenous human MSCs can home specifically to injured regions and efficiently cure rat ARF. These results demonstrate that cell therapy has potential as a novel intervention in ARF.
在本研究中，我们在大鼠急性肾衰竭（ARF）模型中研究了间充质干细胞（MSC）的治疗潜力，并探讨了其可能的体内和体外作用机制。大鼠和人MSC均从骨髓中分离得到。在体外Transwell小室中与损伤的肾组织共培养后，大鼠MSC变成圆形的肾小管上皮样细胞，并高表达细胞角蛋白18（CK18）和水通道蛋白-1（AQP1）等肾标志物。将人MSC注入患有ARF的大鼠体内，并使用显微镜、组织学、PCR、RT-PCR和荧光原位杂交技术对移植后的MSC进行表征。我们发现有更多外源性人MSC定位于损伤的肾组织。移植MSC组的肾脏恢复率高于对照组。检测到与人类肾小管上皮细胞相关的基因，如水通道蛋白-1和甲状旁腺激素受体1。这些发现表明，损伤的肾组织在体外和体内均可诱导大鼠和人MSC分化为肾小管上皮样细胞，外源性人MSC可特异性归巢至损伤区域并有效治愈大鼠ARF。这些结果表明细胞治疗作为ARF的一种新型干预措施具有潜力。
