School of Medicine, Nankai University, Tianjin, 300071, China.
Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Stem Cell Res Ther. 2021 Jul 2;12(1):379. doi: 10.1186/s13287-021-02460-0.
Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear.
In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro.
We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9 cells.
ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.
胚胎干细胞衍生的细胞外囊泡(ESC-EVs)在多种疾病的治疗中具有潜力,被认为是 ES 细胞的替代品。急性肾损伤(AKI)是临床实践中常见的急性和严重疾病,严重威胁着人类的生命和健康。然而,ESC-EVs 对 AKI 的作用和机制尚不清楚。
在这项研究中,我们使用鼠缺血再灌注损伤诱导的 AKI 模型评估了 ESC-EVs 对生理修复和病理修复的影响,接下来研究了其潜在机制。从 ESCs 中分离 EVs,并将源自小鼠成纤维细胞的 EVs 作为治疗对照。然后,我们研究了 ESC-EVs 是否可以通过促进生理修复和抑制 AKI 后病理修复过程来恢复受损肾脏的结构和功能。
我们发现 ESC-EVs 可显著促进受损肾脏的结构和功能恢复。ESC-EVs 增加了肾小管上皮细胞的增殖,促进了肾脏血管生成,抑制了肾纤维化的进展,并挽救了 AKI 后缺血再灌注引起的 DNA 损伤。最后,我们发现 ESC-EVs 通过激活 Sox9 细胞发挥治疗作用。
ESC-EVs 可显著促进 AKI 后的生理修复和抑制病理修复,使受损肾脏的结构和功能得以恢复。这种策略可能成为 ESC 临床应用的一种新的治疗策略。