Wang Wei-Wei, Li Ze-Zheng, Wang Wei, Jiang Yan, Cheng Jin, Lu Shi, Zhang Jin-Yuan
Nephrology Division, Jimin Hospital, Shanghai 200052, China.
Sci Rep. 2015 Jun 5;5:10851. doi: 10.1038/srep10851.
Current therapeutic options for acute kidney injury (AKI) are limited to the use of supportive measures and dialysis. A recent approach that has sparked great interest and gained enormous popularity is the implantation of stem cells to repair acutely damaged kidney organ. Hypoxia inducible factor-1α (HIF-1α) is effective in protecting the kidney from ischemia and nephrotoxicity. In this study, we investigated whether HIF-1α-modified adipose-derived stem cells (ASCs) had an enhanced protective effect on cisplatin-induced kidney injury in vivo. Cisplatin-induced AKI was established in nude mice. Our study demonstrated that HIF-1α-modified ASCs obviously promoted the recovery of renal function, ameliorated the extent of histologic injury and reduced renal apoptosis and inflammation, but HIF-1α-modified ASCs homed to kidney tissues at very low levels after transplantation. In addition, we also found that HIF-1α-modified ASCs significantly increased HO-1 expression in cisplatin-induced AKI in vivo. Thus, our study indicated HIF-1α-modified ASCs implantation could provide advanced benefits in the protection again AKI, which will contribute to developing a new therapeutic strategy for the treatment of AKI.
急性肾损伤(AKI)目前的治疗选择仅限于采取支持措施和进行透析。最近一种引发了极大兴趣并广受欢迎的方法是植入干细胞以修复急性受损的肾脏器官。缺氧诱导因子-1α(HIF-1α)在保护肾脏免受缺血和肾毒性方面具有成效。在本研究中,我们调查了HIF-1α修饰的脂肪来源干细胞(ASC)对顺铂诱导的小鼠体内肾损伤是否具有增强的保护作用。在裸鼠中建立了顺铂诱导的AKI模型。我们的研究表明,HIF-1α修饰的ASC明显促进了肾功能的恢复,改善了组织学损伤程度,并减少了肾脏细胞凋亡和炎症,但移植后HIF-1α修饰的ASC归巢至肾组织的水平非常低。此外,我们还发现HIF-1α修饰的ASC在顺铂诱导的体内AKI中显著增加了HO-1的表达。因此,我们的研究表明,植入HIF-1α修饰的ASC在保护AKI方面可带来更多益处,这将有助于开发一种治疗AKI的新策略。