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.

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients

“…This suggests that smooth muscle cells could be the main receptor cells for miR-486 within the AVM context. Recent papers point out a role for miR-486 in the cardiovascular system, including angiogenesis and myocardial infarction [16,17], or even as a biomarker of cardiac pathologies such as bicuspid aortic disease [18]. Thus, we hypothesize that the increase in miR-486 in exosomes might alter the vascular remodeling, contributing to the development of AVM in HHT.…”

High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis

“…Studies have also shown an increase of miR-486-5p in patients with coronary artery disease ( Niculescu et al., 2015 ). More recently, miR-486-5p enriched in adipose-derived stem cell–EVs have been shown to accelerate the proliferation of skin fibroblasts ( Lu et al., 2020 ). Furthermore, miR-486-5p was shown to reduce ABCA-1 expression in macrophages ( Liu et al., 2016 ) that we reproduced through our studies of BMDM-HG-exo, which in this context could contribute to atherosclerosis acceleration in Apoe −/− mice treated with BMDM–HG-exo, and atherosclerosis in diabetic patients.…”

Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis via transfer of miR-21-5p after cerebral ischemia in mice

“…MiR-22 could regulate endothelial angiogenesis, in ammation, and tissue injury by targeting vascular endothelial-cadherin [51]. MiR-486-5p released by adipose-derived stem cell-derived EV could mediate wound healing and promote angiogenesis [52]. MiR-21-5p could promote extracellular matrix degradation and angiogenesis in the unilateral anterior crossbite model [53].…”