Burgos-Silva Marina, Semedo-Kuriki Patricia, Donizetti-Oliveira Cassiano, Costa Priscilla Barbosa, Cenedeze Marco Antonio, Hiyane Meire Ioshie, Pacheco-Silva Alvaro, Câmara Niels Olsen Saraiva
Nephrology Division, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
Department of Immunology-Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, São Paulo, Brazil.
PLoS One. 2015 Nov 13;10(11):e0142183. doi: 10.1371/journal.pone.0142183. eCollection 2015.
Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.
急性和慢性肾损伤(AKI和CKI)是导致大部分肾衰竭的综合征,目前其死亡率仍然很高。鉴于缺乏更有效的治疗方法,人们一直高度关注使用干细胞来发挥器官保护和再生作用。间充质干细胞(MSCs)在治疗各种免疫性疾病方面已显示出巨大潜力,尽管其作用机制仍存在争议。因此,为了更深入了解MSCs的作用,我们在FVB小鼠叶酸(FA)诱导的肾毒性实验模型中评估了脂肪组织来源干细胞(AdSCs)的作用。接受AdSC治疗的动物在治疗后24小时显示肾功能改善,表现为FA后血清尿素降低。这些数据与通过减少趋化因子表达和中性粒细胞浸润来调节细胞周期和免疫反应相关。FA后4周的长期分析表明,AdSC治疗可减少肾纤维化和慢性炎症。这通过减少间质胶原沉积以及组织趋化因子和细胞因子表达得到证实。因此,我们得出结论,AdSC治疗通过调节炎症和细胞周期,在肾毒性损伤中发挥保护作用,从而减少肾损伤并改善功能,抑制器官纤维化并提供长期免疫调节。