An adipose-derived stem cell-engineered patch represents a promising treatment for chronic wounds

Mesenchymal stem cell (MSC)-based therapies are emerging as promising approach to treat chronic wounds, although uncontrolled/sub-optimal delivery represents a major threat to their wide-spread clinical adoption. Here we report a comprehensive pre-clinical evaluation program on the mechanism of action, efficacy and safety of an easy-to-use patch that concentrates MSC extracted from the human fat (ASCs) in a clinical-grade sponge made of porcine crosslinked-gelatin. ASC were derived from the abdominal/skin fat of four ischemic patients. Microarray data revealed that ASC grown within the patch upregulate the transcription of genes important for wound healing, including VEGF, CXCL12 and FGF7. The patch acted both as a concentrator and a reservoir of ASC-derived factors and sponge-derived fragments having healing capacity. The ASC-patch promoted dermal fibroblast survival, epidermal epithelialization and neovascularization, as shown in a chick chorioallantoic membrane model. No tumor formation was observed in immunodeficient Nude mice subcutaneously transplanted with the ASC-patch. Finally, ASC-patches prepared from syngeneic rats promoted faster healing and re-vascularization of full-thickness skin defects in a pe-clinical rat animal model of ischemic wounds. Together, we provide here compelling pre-clinical evidence that patches concentrating ASCs within crosslinked gelatin may represent a convenient and effective tool for the management of chronic wounds.