Mesenchymal Stem Cell Engineered Nanovesicles for Accelerated Skin Wound Closure.

We report development and characterization of cell-engineered nanovesicles made from mesenchymal stem cells (MSCNVs), which have more than 300 times higher productivity than natural extracellular vesicles (EVs). MSCNVs had similar morphological characteristics to MSCEVs but have molecular characteristics that more resemble MSCs than MSCEVs. In vitro MSCNV treatment increased the proliferation and migration of primary skin fibroblasts and showed better effects than treatment using natural MSCEVs. Quantitative real-time PCR analysis showed increased expression of growth factors in MSCNV-treated skin fibroblasts. Intraperitoneal injection of MSCNVs into syngeneic mice induced mild local inflammation, which resulted in recruitment of immune cells to the injection site. In vivo MSCNV treatment of a mouse skin wound accelerated its healing; this acceleration by MSCNVs may occur by promoting blood vessel formation at the wound site. These results indicate the promise of MSCNVs as agents for regenerative medicine.