Platelet-rich plasma in combination with adipose-derived stem cells promotes skin wound healing through activating Rho GTPase-mediated signaling pathway.

Adipose-derived stem cells (ADSCs) are multipotent stromal cells that provide an abundant source of cells for skin tissue engineering and wound healing. Platelet-rich plasma (PRP) is a concentrate of platelet-rich plasma protein, which contains several different growth factors and other cytokines. In this study, we combined ADSCs with PRP for wound healing. Herein, we found ADSCs in combination with PRP was able to promote wound healing, granulation formation, collagen deposition and re-epithelialization. The mechanism exploration discovered that PRP promoted stress fiber formation in ADSCs, leading to cell migration. Then, we demonstrated that PRP enhanced the expression of Rho GTP family proteins, including Cdc 42, Rac 1 and Rho A. Moreover, it promoted the expression of downstream Rho GTP signaling molecules, including PAK 1, ROCK 2, LIMK 1 and Cofilin. When PRP was used in combination with the Cdc 42 inhibitor ZCL278, the Rho A inhibitor CT04, Rac 1 inhibitor NSC23766, PAK inhibitor FRAX597, or Rock 2 inhibitor Y27632 to treat ADSCs, stress fiber formation was significantly reduced, resulting in decreased cell migration. Our findings may provide a promising approach to promote wound healing.