There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. Researchers from Shanghai Jiao Tong University found that synovium mesenchymal stem cells (SMSCs) have the ability to strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, they overexpressed microRNA-126-3p (miR-126-3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis. The researchers tested a therapeutic strategy involving controlled-release exosomes derived from miR-126-3p-overexpressing SMSCs combined with chitosan. Their in vitro results showed that exosomes derived from miR-126-3p-overexpressing SMSCs (SMSC-126-Exos) stimulated the proliferation of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC-1) in a dose-dependent manner. Furthermore, SMSC-126-Exos also promoted migration and tube formation of HMEC-1. Testing this system in a diabetic rat model, they found that this approach resulted in accelerated re-epithelialization, activated angiogenesis, and promotion of collagen maturity in vivo. These data provide the first evidence of the potential of SMSC-126-Exos in treating cutaneous wounds and indicate that modifying the cells-for example, by gene overexpression-and using the exosomes derived from these modified cells provides a potential drug delivery system and could have infinite possibilities for future therapy.
In vitro experiments to evaluate the effects of SMSC-Exos and SMSC-126-Exos
(A): Proliferation of HMEC-1 and fibroblasts incubated for 0, 1, 3, or 5 days in conditioned medium from days 0 and 6. At each time point of each group, three replicates were used. (B): Representative photographs showing the effect of conditioned medium from days 0 and 6 on the transwell migration and tubule formation of HMEC-1. Three independent experiments were performed to confirm the stability of the phenomenon. Scale bars = 100 μm. (C): Protein phosphorylation levels of ERK1/2 and AKT analyzed by Western blotting. The experiments were performed three times and a representative image is shown. Abbreviations: ERK, extracellular signal-regulated kinase; HMEC-1, human dermal microvascular endothelial cells; p-ERK1/2, phospho-extracellular signal-regulated kinase 1/2; SMSC-126-Exos, exosomes derived from microRNA-126-3p-overexpressing synovium mesenchymal stem cells; SMSC-Exos, synovium mesenchymal stem cell-derived exosomes.