Department of Nephrology, 455th hospital of PLA, Shanghai 200052, China.
Exp Biol Med (Maywood). 2013 Jun;238(6):678-86. doi: 10.1177/1535370213489486.
Bone-marrow mesenchymal stem cells (BMSCs) transplantation is effective for acute kidney injury (AKI) repair but with limited efficiency. In the present study, BMSCs marked by bromodeoxyuridine (BrdU) were transplanted to the AKI mouse model with erythropoietin (EPO) being subcutaneously injected. The blood urea nitrogen (BUN) and serum creatinine (Scr) levels, pathological changes, distribution of BMSCs, expressions of the cytokeratin 18 (CK18) and the stromal cell-derived factor 1 (SDF-1) in the nephridial tissues were measured. The directional migration of BMSCs to the AKI microenvironment in vitro was also tested. The results showed that BMSCs transplantation or EPO injection alone decreased the BUN and Scr levels and the acute tubular necrosis (ATN) scoring in varied degrees. The combination of these decreased the above indicators' levels significantly. BrdU(+) cells (BMSCs) were observed in the AKI nephridial tissues, and CK18 expressed in the cytoplasm of these cells. EPO injection increased the proportion of BrdU(+) cells with the enhanced expression of SDF-1 in the AKI nephridial tissues. EPO increased the migrating number of BMSCs to the AKI microenvironment in vitro, and additional anti-SDF-1 treatment with SDF-1 antibody neutralized this effect. Our results showed that EPO increased the number of the transplanted BMSCs in the injured nephridial tissues and enhanced the AKI repair effect of BMSCs transplantation. The enhanced kidney-homing efficiency for BMSCs mediated by the SDF-1/CXCR4 pathway is one of the possible mechanisms for EPO performance.
骨髓间充质干细胞（BMSCs）移植对急性肾损伤（AKI）的修复有效，但效率有限。在本研究中，通过皮下注射促红细胞生成素（EPO），将溴脱氧尿苷（BrdU）标记的 BMSCs 移植到 AKI 小鼠模型中。测量血尿素氮（BUN）和血清肌酐（Scr）水平、组织病理学变化、BMSCs 的分布、肾组织中细胞角蛋白 18（CK18）和基质细胞衍生因子 1（SDF-1）的表达。还测试了 BMSCs 向 AKI 微环境的体外定向迁移。结果表明，BMSCs 移植或 EPO 注射均可在不同程度上降低 BUN 和 Scr 水平和急性肾小管坏死（ATN）评分。这些组合显著降低了上述指标的水平。在 AKI 肾组织中观察到 BrdU(+)细胞（BMSCs），并且这些细胞的细胞质中表达 CK18。EPO 注射增加了 BrdU(+)细胞的比例，并增强了 AKI 肾组织中 SDF-1 的表达。EPO 增加了 BMSCs 向 AKI 微环境体外迁移的数量，并用 SDF-1 抗体中和 SDF-1 中和这种作用。我们的研究结果表明，EPO 增加了受损肾组织中移植的 BMSCs 的数量，并增强了 BMSCs 移植对 AKI 的修复作用。SDF-1/CXCR4 途径介导的 BMSCs 归巢效率的提高是 EPO 作用的可能机制之一。
