Effects of Platelet Rich Fibrin (PRF) and Adipose-Derived Mesenchymal Stem Cells (ADMSCs) on Wound Healing: Regulating Macrophage Polarization Mechanism

Chronic refractory wounds are common clinical diseases and represent a significant burden to patients. Adipose-derived mesenchymal stem cells (ADMSCs) have been demonstrated to accelerate wound healing. Platelet rich fibrin (PRF) has been used to promote wound sealing, and wound healing. However, the role of ADMSCs/PRF in chronic refractory wounds remains to be elucidated. Cell proliferation was measured by Cell Counting Kit-8. Cell migration was measured using Transwell assay. Concentrations of TNF-alpha and IL-6 in supernatants or plasma were measured using ELISA kits. Collagen deposition was analyzed by Masson's trichrome staining. Quantitative PCR and immunoblots were used to evaluate mRNA and protein expression. PRF significantly promoted the proliferation and migration of ADMSCs. PRF/ADMSCs promotes M1 polarization, suppresses M2 polarization to inhibit inflammatory responses in rat alveolar macrophages. In vivo data suggest that PRF/ADMSCs time-dependently inhibited the levels of inflammatory cytokines, suppressed the levels of M1 surface markers iNOS and CD86, but increased the M2 surface markers Arg-1 and CD206. Moreover, our data also indicate that PRF/ADMSCs significantly time-dependently enhanced collagen deposition of the injury site, and increased the expression of growth factors. NPRF/ADMSCs suppressed M1 polarization, promoted M2 polarization, decreased the levels of inflammatory cytokines to inhibit inflammatory responses, increase levels of growth factors and increase collagen deposition, and therefore speed up wound healing. The findings highlighted the importance of ADMSCs/PRF in the treatment of chronic refractory wounds.