Adipose-Derived Stem Cell to Epithelial Stem Cell Transdifferentiation: A Mechanism to Potentially Improve Understanding of Fat Grafting's Impact on Skin Rejuvenation

Background: Recent evidence suggests that lipofilling improves overlying skin composition and appearance. Adipose-derived stem cells (ADSC) have been implicated. Objective: The authors identify ADSC transdifferentiation into epithelial stem cells through coexpression of GFP+ (green fluorescent protein positive) ADSC with the epithelial stem cell marker p63 in an in vivo fat grafting model. Methods: Six male, GFP+ mice served as adipose tissue donors. Twelve nude mice served as recipients. Recipients were subdivided into 2 arms (6 mice/each arm) and received either whole-fat specimen (group 1) or isolated and purified ADSC + peptide hydrogel carrier (group 2) engrafted into a 1-cm(2) left parascapular subdermal plane. The right parascapular subdermal plane served as control. Skin flaps were harvested at 8 weeks and subjected to (1) confocal fluorescent microscopy and (2) reverse transcriptase polymerase chain reaction (RT-PCR) for p63 mRNA expression levels. Results: Gross examination of skin flaps demonstrated subjectively increased dermal vessel presence surrounding whole-fat and ADSC specimens. The GFP+ cells were seen within overlying dermal architecture after engraftment and were found to coexpress p63. Significantly increased levels of p63 expression were found in the ADSC + hydrogel skin flaps. Conclusions: We offer suggestive evidence that GFP+ ADSC are found within the dermis 8 weeks after engraftment and coexpress the epithelial stem cell marker p63, indicating that ADSC may transdifferentiate into epithelial stem cells after fat grafting. These findings complement current understanding of how fat grafts may rejuvenate overlying skin.