Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression

Abstract

Background: Wound healing is a complex pathophysiological process that involves a variety of cells and cytokines. In this study, we found that local injection of human amnion mesenchymal stem cells into wounds in rats could promote wound healing. Therefore, we hypothesized that the exosomes of human amnion mesenchymal stem cells contain substances that regulate the migration of epidermal cells. It has been reported that miR-135a is involved in cell migration and transformation. However, there have been no reports of its function in skin wound healing. Methods: To test this hypothesis, we injected exosomes overexpressing miR-135a directly into the wound margin. In addition, we tested the migration of BJ cells with overexpression or knockdown of miR-135a in vitro. Additionally, Western blot analysis was used to detect the expression of fibroblast migration-associated proteins after treatment with miR-135a overexpression or knockdown. Results: MiR-135a significantly promoted wound healing compared to the control treatment. Western blot analysis showed a significant downregulation of LATS2 after overexpression of miR-135a. In addition, knockdown of miR-135a effectively attenuated the promoting effect of exosomes on cell migration. Conclusions: Our results indicated that miR-135a promotes wound healing, which may be mediated by downregulating LATS2 levels to increase cell migration. This study provides a rationale for the therapeutic effect on wound healing of miR-135a in exosomes derived from human amnion mesenchymal stem cells.

Hypoxic preconditioning of human urine-derived stem cell-laden small intestinal submucosa enhances wound healing potential

“…Therefore, it is generally believed that the paracrine effect of cells, rather than their differentiation, is the main underlying repair mechanism for stem cell-based therapy [39,40]. As such, several cell-free methods using the secretion of MSCs, such as their condition medium [41,42] or exosomes [43,44], have been introduced to treat skin wounds. Chen et al demonstrated that exosomes derived from human USCs can effectively improve skin cell functions in vitro and obviously enhanced wound healing in diabetic mice [8].…”

Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

“…Our results showed that hAMSCs and hAMSCs-CM efficiently cured heat stress-induced skin injury by inhibiting apoptosis and promoting proliferation of skin cells through activating PI3K/Akt signaling pathway [ 24 ]. Gao et al observed that the exosome-derived miR-135a from hAMSCs promoted cutaneous wound healing and fibroblast migration by downregulating LATS2 levels [ 169 ]. A combined administration of hAMSCs/Matriderm was beneficial to potentiate the therapeutic effects of hAMSCs on wound healing [ 170 ].…”

Extracellular Vesicles in Skin Wound Healing

“…Besides, the significance of AdMSC-EVs cargo MALAT1 (metastasis-associated lung adenocarcinoma transcript 1, a long non-coding RNA) in maintaining fibroblast migration to wound sites was proved since EVs lacking MALAT1 decreased fibroblast migration rate by halving. Other authors determined that fibroblast migration is supported through downregulation of LATS2 (large tumour suppressor 2) levels by miR-135 transferred by human amnion MSC-EVs [ 156 ].…”