Extracellular vesicle-enclosed miR-486-5p mediates wound healing with adipose-derived stem cells by promoting angiogenesis.

Abstract

Adipose-derived stem cells (ASC) are said to have a pivotal role in wound healing. Specifically, ASC-secreted extracellular vesicles (EV) carry diverse cargos such as microRNAs (miRNAs) to participate in the ASC-based therapies. Considering its effects, we aimed to investigate the role of ASC-EVs in the cutaneous wound healing accompanied with the study on the specific cargo-medicated effects on wound healing. Two full-thickness excisional skin wounds were created on mouse dorsum, and wound healing was recorded at the indicated time points followed by histological analysis and immunofluorescence staining for CD31 and α-SMA. Human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMECs) were co-cultured with EVs isolated from ASC (ASC-EVs), respectively, followed by the evaluation of their viability and mobility using CCK-8, scratch test and transwell migration assays. Matrigel-based angiogenesis assays were performed to evaluate vessel-like tube formation by HMECs in vitro. ASC-EVs accelerated the healing of full-thickness skin wounds, increased re-epithelialization and reduced scar thickness whilst enhanced collagen synthesis and angiogenesis in murine models. However, miR-486-5p antagomir abrogated the ASC-EVs-induced effects. Intriguingly, miR-486-5p was found to be highly enriched in ASC-EVs, exhibiting an increase in viability and mobility of HSFs and HMECs and enhanced the angiogenic activities of HMECs. Notably, we also demonstrated that ASC-EVs-secreted miR-486-5p achieved the aforesaid effects through its target gene Sp5. Hence, our results suggest that miR-486-5p released by ASC-EVs could be a critical mediator to develop an ASC-based therapeutic strategy for wound healing.

• Authors: Yingjie Lu, Huicai Wen, Jinjun Huang, Peng Liao, Huaiwei Liao, Jun Tu, Yuanlin Zeng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 17 Pg. 9590-9604 (09 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32666704 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• MIRN486 microRNA, human
• MicroRNAs

Topics

• Adipocytes (metabolism, pathology)
• Adipose Tissue (metabolism, pathology)
• Adult
• Aged
• Cells, Cultured
• Cicatrix (metabolism, pathology)
• Endothelial Cells (metabolism, pathology)
• Extracellular Vesicles (metabolism, pathology)
• Female
• Fibroblasts (metabolism, pathology)
• Humans
• MicroRNAs (metabolism)
• Middle Aged
• Neovascularization, Pathologic (metabolism, pathology)
• Skin (metabolism, pathology)
• Stem Cells (metabolism, pathology)
• Wound Healing (physiology)