Exosome­guided phenotypic switch of M1 to M2 macrophages for cutaneous wound healing

Abstract

Macrophages (M&#981

s) critically contribute to wound healing by coordinating inflammatory, proliferative, and angiogenic processes. A proper switch from proinflammatory M1 to anti&#8208

inflammatory M2 dominant M&#981

s accelerates the wound healing processes leading to favorable wound&#8208

care outcomes. Herein, an exosome&#8208

guided cell reprogramming technique is proposed to directly convert M1 to M2 M&#981

s for effective wound management. The M2 M&#981

&#8208

derived exosomes (M2&#8208

Exo) induce a complete conversion of M1 to M2 M&#981

s in vitro. The reprogrammed M2 M&#981

s turn Arginase (M2&#8208

marker) and iNOS (M1&#8208

marker) on and off, respectively, and exhibit distinct phenotypic and functional features of M2 M&#981

s. M2&#8208

Exo has not only M&#981

reprogramming factors but also various cytokines and growth factors promoting wound repair. After subcutaneous administration of M2&#8208

Exo into the wound edge, the local populations of M1 and M2 M&#981

s are markedly decreased and increased, respectively, showing a successful exosome&#8208

guided switch to M2 M&#981

polarization. The direct conversion of M1 to M2 M&#981

s at the wound site accelerates wound healing by enhancing angiogenesis, re&#8208

epithelialization, and collagen deposition. The M&#981

phenotype switching induced by exosomes possessing the excellent cell reprogramming capability and innate biocompatibility can be a promising therapeutic approach for various inflammation&#8208

associated disorders by regulating the balance between pro&#8208

versus anti&#8208

inflammatory M&#981

s.