顺铂广泛应用于肿瘤化疗，但肾毒性是顺铂不可避免的副作用。多项研究表明间充质基质细胞（MSC）可改善顺铂诱导的肾损伤，但其潜在机制尚不清楚。本研究通过顺铂单次腹腔注射建立顺铂肾损伤小鼠模型。注射顺铂前一小时，小鼠通过转染或不转染 siRNA、重组人肿瘤坏死因子 (TNF)-α 刺激的基因/蛋白 6 (rhTSG-6) 或 PBS 接受人骨髓 MSC (hBM-MSC)。尾静脉。此外，顺铂刺激的 HK-2 细胞用 hBM-MSC 或 rhTSG-6 处理。 hBM-MSCs 治疗显着改善了顺铂引起的急性和慢性肾损伤，血清肌酐 (Scr)、血尿素氮 (BUN)、肾小管损伤、胶原蛋白沉积、α-平滑肌肌动蛋白积累以及炎症反应，以及肾组织中抗炎因子表达和 Treg 细胞浸润显着增加。此外，我们发现只有少数hBM-MSCs移植到受损的肾脏中，并且在施用hBM-MSCs后，小鼠血清中的人TSG-6水平显着增加。此外，hBM-MSC 显着增加了受损 HK-2 细胞的活力，并降低了培养上清液中炎症细胞因子的水平。然而，hBM-MSC 中 TSG-6 基因的敲低显着削弱了它们在体内和体外的有益作用。相反，用rhTSG-6处理获得了与hBM-MSC类似的有益效果。我们的结果表明，hBM-MSC 的全身给药可部分通过旁分泌 TSG-6 分泌来减轻顺铂引起的急性和慢性肾损伤。© 作者 2024。由牛津大学出版社出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需更多信息，请联系journals.permissions@oup.com。

Cisplatin is widely employed in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rhTSG-6), or PBS through tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. hBM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen (BUN), tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, knockdown of TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviate cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.