Genetically modified adipose-derived stem cells with matrix metalloproteinase 3 promote scarless cutaneous repair

Adipose-derived stem cells (ASCs) possess strong regenerative potencies and have been used to improve wound healing in animal models and clinical studies. However, the use of ASCs on scarless wound healing is not satisfactory. Matrix metalloproteinase 3 (MMP-3) is involved in extracellular matrix (ECM) remolding and scar formation. We aimed to investigate the effect of ASCs stable expressing MMP-3 (ASCs-MMP-3) on wound healing and scarring. A cutaneous wound healing animal model was used to assess the effect of ASCs and ASCs-MMP-3 on wound healing and scar formation. The target protein levels in the wound tissues were determined by western blot assay. Our results demonstrated that ASCs alone promoted wound healing but had a negligible effect on reducing scarring. ASCs-MMP-3 not only possessed the ability of ASCs to speed up wound healing, but also incorporated the capability of MMP-3 to reduce scaring. Overexpressing of MMP-3 decreased the collagen I, transforming growth factor (TGF)-beta 1, and alpha-smooth muscle actin (alpha-SMA) levels and enhanced collagen III and TGF-beta 3 levels which contributed to reducing scar formation. Our studies suggested that ASCs-MMP-3 is a potential candidate for developing effective therapeutic strategies for scarless wound healing.