Melatonin promotes survival of nonvascularized fat grafts and enhances the viability and migration of human adipose‐derived stem cells via down‐regulation of acute inflammatory cytokines

Non-vascularized fat grafting is a valuable technique for soft tissue reconstruction but poor survival of fat in the host environment remains a problem. A process known as cell-assisted transfer is used to enhance fat graft retention by adding stromal vascular fraction, an adipose-derived stem cell (ASC) rich content to lipoaspirate. We have recently shown that the use of melatonin, a ROS scavenger, protects human ASCs from hydrogen peroxide induced oxidative stress and cell death in vitro but its role as a pharmacologic adjunct in clinical fat grafting has not been studied. Herein, we examined the effect of melatonin on human ASCs in-vitro using survival and functional assays including the MTT assay, CellTox Green assay, monolayer scratch assay as well as a human cytokine chemoluminescence and TNF-alpha assay. We further tested the effect of melatonin-treated fat grafts in-vivo with a murine model. Hematoxylin and eosin staining, perilipin and CD31 immunostaining were performed with morphometric analysis of adipose tissue. Our results demonstrated that in vitro, the addition of melatonin to ASCs significantly improved their cell-viability, promoted cell migration and preserved membrane integrity as compared to controls. In addition, it induced a potent anti-inflammatory response by down-regulating acute inflammatory cytokines particularly TNF-alpha. For the first time, we demonstrate in-vivo that melatonin enhances fat graft volume retention by reducing inflammation and increasing the percentage of adipose volume within fat grafts with comparable volumes to that of cell-assisted lipotransfer. Based on our novel findings, melatonin may be a useful pharmacological adjunct in clinical fat grafting.