Begum Sumreen, Ahmed Nazia, Mubarak Muhammed, Mateen Syeda Mamoona, Khalid Nida, Rizvi Syed Adibul Hasan
Stem Cells Research Laboratory (SCRL).
Clinical Laboratory Sciences (CLS).
Int J Stem Cells. 2019 Mar 30;12(1):125-138. doi: 10.15283/ijsc18091.
In regenerative medicine, mesenchymal stem cells derived from adipose tissues (Ad-MSCs) are a very attractive target to treat many diseases. In relation to nephrology, the aim of the current study is to investigate the effects of Ad-MSCs for the amelioration of acute kidney injury and to explore the mechanism of renal parenchymal changes in response to allogeneic transplantation of Ad-MSCs.
The nephrotoxicity was induced by cisplatin (CP) in balb/c mice according to RIFLE Class and AKIN Stage 3. PCR, qRT-PCR and fluorescent labeled cells infusion, histopathology, immunohistochemistry, functional analyses were used for genes and proteins expressions data acquisition respectively. We demonstrated that single intravenous infusion of 2.5×10/kg mAd-MSCs in mice pre-injected with CP recruited to the kidney, restored the renal structure, and function, which resulted in progressive survival of mice. The renal tissue morphology was recovered in terms of diminished necrosis or epithelial cells damage, protein casts formation, infiltration of inflammatory cells, tubular dilatation, and restoration of brush border protein; Megalin and decreased Kim-1 expressions in mAd-MSCs transplanted mice. Significant reduction in serum creatinine with slashed urea and urinary protein levels were observed. Anti-BrdU staining displayed enhanced tubular cells proliferation. Predominantly, downgrade expressions of TNF- and TGF-1 were observed post seven days in mAd-MSCs transplanted mice.
Ad-MSCs exerts pro-proliferative, anti-inflammatory, and anti-fibrotic effects. Ad-MSCs transplantation without any chemical or genetic manipulation can provide the evidence of therapeutic strategy for the origin of regeneration and overall an improved survival of the system in functionally deprived failed kidneys.
在再生医学中，脂肪组织来源的间充质干细胞（Ad-MSCs）是治疗多种疾病的极具吸引力的靶点。就肾脏病学而言，本研究旨在探讨Ad-MSCs对改善急性肾损伤的作用，并探索同种异体移植Ad-MSCs后肾实质变化的机制。
根据RIFLE分级和AKIN分期3，用顺铂（CP）诱导balb/c小鼠产生肾毒性。分别采用PCR、qRT-PCR和荧光标记细胞输注、组织病理学、免疫组织化学、功能分析获取基因和蛋白质表达数据。我们证明，在预先注射CP的小鼠中单次静脉输注2.5×10/kg mAd-MSCs可募集至肾脏，恢复肾脏结构和功能，从而使小鼠逐渐存活。肾组织形态在坏死减轻、上皮细胞损伤、蛋白管型形成、炎性细胞浸润、肾小管扩张以及刷状缘蛋白恢复方面得到恢复；Megalin和Kim-1在mAd-MSCs移植小鼠中的表达降低。观察到血清肌酐显著降低，尿素和尿蛋白水平大幅下降。抗BrdU染色显示肾小管细胞增殖增强。主要地，在mAd-MSCs移植小鼠中，7天后观察到TNF-和TGF-1的表达下调。
Ad-MSCs具有促增殖、抗炎和抗纤维化作用。未经任何化学或基因操作的Ad-MSCs移植可为再生起源的治疗策略提供证据，并总体上改善功能丧失的衰竭肾脏系统的存活率。
