Exosomal microRNA-125a-3p from human adipose-derived mesenchymal stem cells promotes angiogenesis of wound healing through inhibiting PTEN.

Angiogenesis plays a key in the process of tissue repair and wound healing. Human adipose-derived mesenchymal stem cells (HADSCs) have been found to act a promotion role during angiogenesis. Moreover, miR-125a-3p in HADSCs could promote the angiogenesis of HUVECs, but their specific mechanism in wound healing needs further study. Western blotting and qRT-PCR were used for detecting the protein and mRNA level, respectively. Exosomes were isolated successfully, and transmission electron microscope was used to identify exosomes. Angiogenesis, cell migration, and proliferation were detected with tube formation, wound healing, and MTT assays. The interactions of miR-125a-3p and PTEN were validated using dual-luciferase reporter assay. Animal model was used to evaluate the effect of miR-125a-3p on wound healing. HADSCs-exosome remarkably promoted the viability, migration, and angiogenesis of HUVECs. Knockdown of miR-125a-3p in HADSCs could inhibit the effect of HADSCs-exosome, while overexpression of miR-125a-3p could further promote the effect of HADSCs-exosome on HUVECs. MiR-125a-3p from HADSCs-exosome inhibited the expression of PTEN in HUVECs. Knockdown of PTEN promoted the viability, migration, and angiogenesis of HUVECs and reversed the effect of miR-125a-3p knockdown on HUVECs. Finally, miR-125a-3p from HADSCs-exosome could promote wound healing and angiogenesis in mice by inhibiting PTEN in mice wound granulation tissues. MiR-125a-3p from the HADSCs-exosome promoted the wound healing and angiogenesis, and these effects were achieved through regulating PTEN. This study may provide a new thought for the treatment and prevention of tissue repair.

Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis.

It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and ß-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/ß-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.

LncRNA MALAT1 from human adipose-derived stem cell exosomes accelerates wound healing via miR-378a/FGF2 axis.

Aim: The effects of MALAT1 from human adipose-derived stem cell (ADSC) exosomes in skin wound healing were investigated. Material & methods: The viability, apoptosis and migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometry and scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosis and inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2 expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

Skin wound healing is a process of synergistic action of multiple factors. Adipose-derived stem cells (ADSCs), a group of stem cells, are recruited into damaged tissues and secret several cytokines, which promote nascent tissue formation. ADSC-derived exosomes play crucial roles in wound healing as a paracrine vehicle for delivering chemokines, growth factors and RNAs to host cells. LncRNAs are involved in multiple physiological processes, including tissue repair. Furthermore, lncRNA MALAT1 is associated with endothelial cell migration and angiogenesis in different types of diseases. This study demonstrated that hADSC exosomes promoted the proliferation and migration of human skin fibroblasts and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited human skin fibroblast viability and migration, promoted apoptosis and suppressed angiogenesis by upregulating miR-378a. miR-378a overexpression inhibited the phenotypic characteristics of human skin fibroblasts by downregulating FGF2. Exosomal MALAT1 appeared to accelerate skin wound healing by mediating the miR-378a/FGF2 axis.