Effect of MicroRNA-146a Modified Adipose-Derived Stem Cell Exosomes on Rat Back Wound Healing

Abstract

Objective: To investigate the effect of MicroRNA-146a modified adipose-derived stem cell exosomes on the proliferation and migration of fibroblasts and the therapeutic effect on wound healing. Methods: Culture and identification of human adipose-derived stem cells (hASCs), miRNA-146a minic vector was constructed and transfected into hASCs, the exosomes of the empty group and overexpression group were extracted, identified, and quantitatively analyzed after 24 h of successful transfection. The exosomes were added into National Institute of Health Mouse Embryonic Fibroblasts (NIH/3T3) and cultured for 48 h, the proliferation and migration ability of NIH/3T3 fibroblasts was detected. The expression of serpin family H member 1 (SERPINH1) and phosphorylated extracellular regulated protein kinase (p-ERK) was detected by Western blot. The model of back wound was established. The exosomes were injected into 4 different sites with the shape of “cross” around the wound, and the scar diameter of the skin defect was measured at 3, 7, and 11 days, the skin of the defect was taken on the 14th day. platelet endothelial cell adhesion molecule-1 (CD31) was detected by immunofluorescence staining to evaluate angiogenesis, and Western blot was used to detect the expression of SERPINH1 and p-ERK. Results: The miR-146a mimic-exosome promoted the proliferation and migration of fibroblasts, and the expression of SERPINH1 and p-ERK2 was up-regulated. After the rats were treated with exosomes, the wound area decreased rapidly, neovascularization was promoted, and the expression of SERPINH1 and p-ERK2 was up-regulated. Conclusions: MicroRNA-146a modified adipose stem cell exosomes could regulate the expression of SERPINH1 and p-ERK, promote the migration and proliferation of fibroblasts, and neovascularization to promote the wound healing of rat back.

Advances in microRNA from adipose-derived mesenchymal stem cell-derived exosome: focusing on wound healing

“…It is worth mentioning that the already mentioned Exo-related advantages create the possibility for its manufacturing of clinical-grade products on a commercial scale, and the US miRNA market is reported to have exceeded US $98.6 million in revenue in 2015. 160 These data all demonstrate that miRNA therapy has clinical value and great potential in the field of wound healing.…”

“…159 Modified ADMSC-Exo transfected with miR-146a was capable of upregulating Serpin family H member 1 (SERPINH1), phosphorylated extracellular regulated protein kinase (P-ERK), migration, proliferation of fibroblasts, neovascularization, and wound healing in rats. 160 The survival and proliferation of ADMSCs were significantly increased by hypoxia induction, as found by Wang et al 58 It is possible that up-regulated miR-21-3p/miR-126-5p/miR-31-5p and down-regulated miR-99b/miR-146-a promote the proliferation and migration of fibroblasts by ADMSC-Exo (100 μg mL −1 ) as well as regulate immune responses by activating PI3K/AKT pathways, thus markedly promoting wound healing. As can be seen, ADMSC-Exo-miRNA possesses good therapeutic potential for promoting cell proliferation, vascular repair, or inhibition of inflammatory processes.…”

Exosome derived from stem cell: A promising therapeutics for wound healing

“…Studies have found that EdSC can induce benefits in nearly all phases of wound healing. For instance, it can inhibit inflammation, control immune responses, and promote cell proliferation and angiogenesis ( He et al, 2019 ; Chen Md et al, 2021 ).…”

“…In the phase of re-epithelialization, fibroblasts proliferate and migrate in large numbers and produce and deposit ECM to form granulation tissues that replace initial fibrin clots and repair tissue losses ( Wilkinson and Hardman, 2020 ). EdSCs were readily taken up by fibroblasts that stimulate cell activity to promote wound healing ( Hu et al, 2016 ; Chen Md et al, 2021 ; Tutuianu et al, 2021 ). As a scaffold, granulation tissue supports migration as well as the proliferation of wound cells and promotes new angiogenesis.…”

Cell‐free therapy based on stem cell‐derived exosomes: A promising approach for wound healing

“…Furthermore, the wound area rapidly decreased and neovascularisation was stimulated to enhance the wound healing on the backs of rats (Figure 2C). 78 Wound closure rate, epithelial regeneration and skin remodelling were accelerated by hUCMSC‐exos encapsulated in a thermosensitive PF‐127 hydrogel to a full‐thickness cutaneous wound in a STZ‐induced diabetic rat model 79 . Skin wound healing could be effectively promoted by exosomes derived from gingival mesenchymal stem cells (GMSCs) loaded chitosan/silk hydrogel sponge in diabetic rats by promotion of the deposition, re‐epithelialisation and remodelling of collagen as well as by enhancement of neuronal ingrowth and angiogenesis 80 .…”