Systemic Administration of Adipose-Derived Stromal Cells Concurrent with Fat Grafting

Abstract

Background: Cell-assisted lipotransfer, a technique involving free fat grafting mixed with adipose-derived stromal cells, has gained popularity for enhancing fat graft retention. In terms of stem cell delivery, intravenous injection can be a novel alternative with clinical value. However, the effects of intravenously injected adipose-derived stromal cells concurrent with fat grafting have not been described. The authors investigated the histologic and microenvironmental changes in grafted fat when adipose-derived stromal cells were injected intravenously concurrent with grafting.

Methods: Using a modified animal model of cell-assisted lipotransfer, adipose tissue from green fluorescent protein-expressing C57BL/6J (B6) mice was grafted into recipient wild-type B6 mice, followed by intravenous injection of adipose-derived stromal cells from DsRed-expressing B6 mice. The distribution of adipose-derived stromal cells was evaluated using bioluminescent imaging, and graft volume was measured using micro-computed tomographic scans. Donor fat and adipose-derived stromal cells were traced using immunofluorescent staining.

Results: The authors identified the recruitment of adipose-derived stromal cells inside the graft after intravenous injection of adipose-derived stromal cells concurrent with grafting despite the arrest of cells in the lungs. Intravenous injection of adipose-derived stromal cells resulted in significantly higher adipogenesis gene expression, retention of graft volume, and vascular density of the graft. A tracing study performed until postoperative week 8 revealed that intravenously injected adipose-derived stromal cells mainly induced angiogenesis and adipogenesis by paracrine action rather than direct differentiation.

Conclusions: Consistent with results of cell-assisted lipotransfer, adipose-derived stromal cell supplementation by systemic administration led to improved retention of the fat graft. The findings broaden the surgical options for fat grafting and enhance the clinical value of cell-assisted lipotransfer.