Premium
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
Author(s) -
Tan Shaun S.,
Zhan Weiqing,
Poon Christopher J.,
Han Xiaolian,
Marre Diego,
Boodhun Sholeh,
Palmer Jason A.,
Mitchell Geraldine M.,
Morrison Wayne A.
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2463
Subject(s) - melatonin , adipose tissue , stromal vascular fraction , stem cell , transplantation , viability assay , proinflammatory cytokine , in vivo , stromal cell , perilipin , chemistry , inflammation , medicine , andrology , adipocyte , biology , microbiology and biotechnology , cell , biochemistry
Nonvascularized 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 reactive oxygen species scavenger, protects human ASCs from hydrogen peroxide‐induced oxidative stress and cell death in vitro but its role as a pharmacological adjunct in clinical fat grafting has not been studied. Herein, the effect of melatonin was examined 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 tumour necrosis factor‐α assay. Further, the effect of melatonin‐treated fat grafts was tested in vivo with a murine model. Haematoxylin and eosin staining, perilipin and CD31 immunostaining were performed with morphometric analysis of adipose tissue. The results demonstrate 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 downregulating acute inflammatory cytokines particularly tumour necrosis factor‐α. For the first time, it is demonstrated 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 these novel findings, melatonin may be a useful pharmacological adjunct in clinical fat grafting.