Engineered BMSCs-Derived Exosomal miR-542-3p Promotes Cutaneous Wound Healing

Abstract

Background: The healing of cutaneous wounds requires better strategies, which remain a challenge. Previous reports indicated that the therapeutic function of mesenchymal stem cells is mediated by exosomes. This work demonstrated the regenerative effects of engineered BMSCs-derived Exosomal miR-542-3p in skin wound mouse models. Methods: Bone marrow mesenchymal stem cells (BMSCs) -derived exosomes (BMSCs-Exos) were isolated by ultracentrifugation and identified by Transmission Electron Microscope (TEM) and Nanoparticle Tracking Analysis (NTA). BMSCs-Exo loaded with miRNA-542-3p by electroporation. We explored the effects of miRNA-542-3p-Exo on the proliferation and migration of Human Skin Fibroblasts (HSFs)/Human dermal microvascular endothelial cells (HMECs). In addition, The angiogenesis of HMECs was detected by Tube formation assay in vitro. The effects of miRNA-542-3p-Exo in the skin wound mouse model were detected by H&E staining, Masson staining, and immunofluorescence analysis. We assessed the effect of miRNA-542-3p-Exo on collagen deposition, new blood vessel formation, and wound remodeling in a skin wound mouse model. Results: MiRNA-542-3p-Exos could be internalized by HSFs/HMECs and enhance the proliferation, migration, and angiogenesis of HSFs/HMECs in vitro and in vivo. The protein expression of collagen1/3 was significantly increased after miRNA-542-3p-Exo treatment in HSFs. In addition, the local injection of miRNA-542-3p-Exo promoted cellular proliferation, collagen deposition, neovascularization, and accelerated wound closure. Conclusion: ConclusionThis study suggested that miRNA-542-3p-Exo can stimulate HSFs/HMECs function. The treatment of miRNA-542-3p-Exo in the skin wound mouse model significantly promotes wound repair. The therapeutic potential of miRNA-542-3p-Exo may be a future therapeutic strategy for cutaneous wound healing.

Bone marrow mesenchymal stem cell‑derived exosomes: A novel therapeutic agent for tendon‑bone healing (Review)

“…Li et al (118) first described that TGF-β1 treatment promoted BMSc-EXO secretion, and miR-29a promoted tendon cell proliferation, migration and fibrosis by targeting fatty acid binding protein 3, thereby improving tendon injury and Rc tear. Several previous studies have shown that BMScs-EXOs can promote skin wound healing by regulating the activation and proliferation of fibroblasts (119)(120)(121). Recently, Li et al (122) confirmed that BMSC-EXOs also play a critical role in promoting tendon-bone healing by promoting the proliferation and differentiation of fibroblasts.…”

Exosomal microRNA-Based therapies for skin diseases

“…Xiong et al. [ 38 ] found that the expression of miR-542-3p in the damaged skin of mice was significantly lower than that in normal skin; therefore, they used miR-542-3p to promote wound healing. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (BMSC-Exos) were isolated using ultracentrifugation, and then loaded with miRNA-542-3p by electroporation.…”

Advancements in engineered exosomes for wound repair: current research and future perspectives

“…Electroporation, a relatively straightforward method, involves creating pores in the exosome membrane using high voltage, allowing for the loading of external target molecules near the endosomal cavity ( Gilligan and Dwyer, 2017 ). Xiong et al (2023) reported that miR-542-3p targeted stimulation of human skin fibroblasts (HSFs)/human dermal microvascular endothelial cells (HMECs), and successfully modified exosomes to target the wound healing mechanism by introducing miR-542-3p into bone marrow mesenchymal stem cells (BMSCs) by electroporation. This modification enhanced the exosome’s pro-angiogenic and pro-cell proliferative effects, enabling effective wound treatment ( Yan et al, 2022 ).…”