Human adipose-derived stem cells in fibrin glue carrier modulate wound healing phases in rats

Abstract

Cell-based therapy using human adipose-derived stem cells (ADSCs) is a new approach for enhancing wound healing. Therefore, in this study, we aimed to evaluate the immunomodulatory effect and wound healing process based on xenografted human ADSCs in a fibrin glue matrix carrier during the wound healing process in a full-thickness excisional model in rats. Two excisional wounds were made in the dorsum of 60 rats using a dermatological punch (1.5 cm diameter), and the rats were randomly assigned to three groups: control (untreated group), FG (topical treatment of both wounds with fibrin glue), and ADSC+FG (topical treatment of both wounds with 2.0 × 10 5 ADSCs in fibrin glue carrier). On the 2nd, 7th, 14th, and 21st days after the wounding surgical process, re-epithelialization was assessed by imaging the skin/wound/scar, and samples were harvested for histomorphometric analyses (quantification of inflammatory cells, blood vessels, fibroblasts, and collagen); biochemical quantification of myeloperoxidase (neutrophil), N-acetylglucosaminidase (macrophage), hydroxyproline (total collagen), and glycosaminoglycans; immunohistochemistry to detect IL-10 and IL-17; and western blot analysis of TNF-α, TGF-β1, and VEGF. ADSC+FG therapy stimulated the anti-inflammatory response up to the 7th day, where the IL-10 levels were higher compared with the control group. This treatment induced angiogenesis, fibroblast proliferation, and collagen formation faster than the other treatments to enhance re-epithelialization. ADSC and FG therapy could be suitable for modulating the inflammatory response and enhancing re-epithelialization, as well as the formation of new blood vessels during wound healing.