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骨髓间充质干细胞通过细胞外囊泡的旁分泌作用减少大鼠模型中的输尿管狭窄形成。

Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles.

机构信息

Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Department of Urology, The First Affiliated Hospital of University of South China, Hengyang, China.

出版信息

J Cell Mol Med. 2018 Sep;22(9):4449-4459. doi: 10.1111/jcmm.13744. Epub 2018 Jul 11.

DOI:10.1111/jcmm.13744
PMID:29993184
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6111875/
Abstract

With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs-derived EVs (MSC-EVs) treatment in a pre-clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC-EVs (administration via renal-arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC-EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor-β1 induced fibration. Due to MSC-EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC-EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US.

摘要

由于缺乏有效的治疗方法来预防或治疗输尿管狭窄（US），这是一种医源性输尿管损伤后的多因素纤维化疾病，因此急需新的治疗方法。间充质干细胞（MSCs）已广泛用于治疗组织缺陷和过度纤维化，最近的研究表明，MSCs 的主要治疗载体之一包含在其细胞外囊泡（EVs）的分泌组中。因此，我们决定探索 MSC-EVs（MSC 衍生的 EVs）治疗在 US 临床前模型中的特定作用。结果首先表明，无论是 MSC 的单次剂量还是 MSC-EVs 的单次剂量（通过肾动脉给药），均可显着改善 US 大鼠模型中的输尿管纤维化并恢复输尿管形态发育。通过 MSC 或 MSC-EVs 治疗减轻肾积水、肾功能障碍较轻和抑制转化生长因子-β1 诱导的纤维化，我们证实了我们的观察结果。由于 MSC-EVs 是 MSC 的等效剂量，并且观察到移植 MSC 和 MSC-EVs 的疗效相似，因此我们推测 MSC 治疗 US 的疗效可能是由于旁分泌机制释放 EVs。我们的研究为大鼠 US 模型中对抗输尿管狭窄形成提供了一种创新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/157a/6111875/ad7e28eebba2/JCMM-22-4449-g007.jpg
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