Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School of Rehabilitation Medicine,Weifang Medical University, Shandong Province, China.
Biochem Biophys Res Commun. 2020 Jan 29;522(1):205-212. doi: 10.1016/j.bbrc.2019.11.006. Epub 2019 Nov 20.
Renal CD133 + scattered tubular cells (STCs) have been regarded as progenitor-like cells in the kidney and participated in ischemic renal injury repair. However, the mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the protective effect of CD133 + STCs depends on the transfer of mitochondria to injured tubular cells in vitro. In this study, renal ischemic reperfusion injury (IRI) rat model was established with one side kidney ischemic for 45 min and animals were sacrificed at 48 h after operation. Tubular cells were isolated and cultured in vitro, and then CD133 + STCs were selected from the cultured cells. Then, CD133 + STCs were co-cultured with CD133-tubular cells (TECs) to detect the tunneling nanotubes like structures, and the transfer of mitochondria from CD133 + STCs to injured tubular cells were detected by fluorescent imaging and flow cytometry. Further, cellular protective effects of CD133 + STCs were tested when cultured with TECs under hypoxic conditions. In results, renal CD133 + STCs were scattered throughout the normal kidney and increased upon ischemic injury. Nanotube formations were commonly found between CD133 + STCs and TECs, and the transfer of mitochondria was detected from CD133 + STCs to TECs. Further, CD133 + STCs exist significant anti-apoptosis and pro-proliferation effects for TECs under hypoxic culture conditions. Thus, this study was first described that renal CD133 + STCs could transfer mitochondria to injured TECs in vitro for its protective effects, which revealed an important novel mechanism for renal repair after ischemic injury.
肾 CD133+散在的管状细胞 (STCs) 被认为是肾脏中的祖细胞样细胞，并参与缺血性肾损伤修复。然而，其作用机制尚未完全阐明。本研究的主要目的是验证 CD133+STCs 的保护作用依赖于其向受损管状细胞转移线粒体的假说。本研究建立了单侧肾脏缺血 45 分钟的肾缺血再灌注损伤 (IRI) 大鼠模型，术后 48 小时处死动物。体外分离和培养管状细胞，从培养的细胞中选择 CD133+STCs。然后，将 CD133+STCs 与 CD133-管状细胞 (TECs) 共培养，检测隧道纳米管样结构，并通过荧光成像和流式细胞术检测 CD133+STCs 向受损管状细胞转移的线粒体。进一步，在缺氧条件下与 TEC 共培养时，检测 CD133+STCs 的细胞保护作用。结果显示，正常肾脏中 CD133+STCs 呈散在分布，缺血损伤后增加。在 CD133+STCs 和 TECs 之间常见纳米管形成，并且从 CD133+STCs 向 TECs 检测到线粒体转移。此外，在缺氧培养条件下，CD133+STCs 对 TECs 具有显著的抗凋亡和促增殖作用。因此，本研究首次描述了肾脏 CD133+STCs 可以在体外将线粒体转移到受损的 TECs 中，发挥其保护作用，这揭示了缺血性损伤后肾脏修复的一个重要新机制。
