Cell Therapy Center, Severance Hospital, Seoul, 03722, Republic of Korea.
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Sci Rep. 2022 Feb 17;12(1):2776. doi: 10.1038/s41598-022-06824-1.
Stem cell-derived exosomes are efficient and safe therapeutic tools for transferring endogenous biological cargo or functional biomolecules for regenerative medicine. The regulation of inflammation and angiogenesis plays a pivotal role in wound healing and tissue regeneration. The purpose of this study was to investigate the anti-inflammatory and pro-angiogenic roles of human adipose mesenchymal stem cell-derived exosomes, focusing on the underlying mechanisms. Exosomes inhibited LPS-induced inflammation by activating ROCK1 and PTEN expression. Moreover, microRNAs (miR-132 and miR-146a) released from exosomes upregulated the expression of pro-angiogenic genes and promoted proliferation activity and tube formation in human umbilical vein endothelial cells. Exosomal effects were verified using ROCK1/PTEN inhibitors for anti-inflammation and miR-132/miR-146a inhibitors for pro-angiogenesis. Our findings suggest that exosomes exert anti-inflammatory effects by targeting the ROCK1/PTEN pathway and exhibit pro-angiogenic effects via delivery of miR-132 and miR-146a. Taken together, these results suggest that exosomes may be promising therapeutic candidates for curing diseases involved in inflammation and angiogenesis.
干细胞衍生的外泌体是传递内源性生物货物或功能性生物分子用于再生医学的有效和安全的治疗工具。炎症和血管生成的调节在伤口愈合和组织再生中起着关键作用。本研究旨在探讨人脂肪间充质干细胞衍生的外泌体的抗炎和促血管生成作用,重点研究其潜在机制。外泌体通过激活 ROCK1 和 PTEN 表达抑制 LPS 诱导的炎症。此外,外泌体释放的 microRNAs(miR-132 和 miR-146a)上调了促血管生成基因的表达,并促进了人脐静脉内皮细胞的增殖活性和管形成。使用 ROCK1/PTEN 抑制剂进行抗炎和 miR-132/miR-146a 抑制剂进行促血管生成来验证外泌体的作用。我们的研究结果表明,外泌体通过靶向 ROCK1/PTEN 通路发挥抗炎作用,并通过递送 miR-132 和 miR-146a 发挥促血管生成作用。总之,这些结果表明,外泌体可能是治疗涉及炎症和血管生成的疾病的有前途的治疗候选物。