Effect of exogenous adipose-derived stem cells in the early stages following free fat transplantation

Abstract

Abstract. Cotransplantation of adipose-derived stem cells (ASCs) is an effective therapeutic approach for enhancing the survival of transplanted fat tissue; however, the role of ASCs in free fat transplantation remains unclear. In the present study, fat harvested from C57BL/6 mice expressing green fluorescent protein was injected subcutaneously into the back of C57BL/6 mice, who also received ASCs (group A) or received the fat tissue only (group B). The grafts were harvested at days 1, 4, 7, 14, 30 and 90 following the transplantation. Graft volume and histology were evaluated, and the secretion levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were quantified using enzyme-linked immunosorbent assays. No statistically significant difference was identified between groups A and B in the graft survival rate up to day 14 following the aspirated fat transplantation; however, the graft survival rate decreased during the following 14-90 days. Initially, group =A exhibited a higher graft survival rate and a greater degree of angiogenesis compared with group B. The ratio of dead cells was not significantly different between the two groups on day 1; however, group A had a greater number of living interstitial cells compared with group B at the later time points. The secretion of VEGF by the ASCs had an earlier peak time in group A (day 4) compared with group B (day 7). In addition, the secretion of HGF in group A was greater compared with group B. Therefore, the role of exogenous ASCs in free fat transplantation may not directly participate in angiogenesis and adipogenesis, but may promote the survival ratio of the graft-resident interstitial cells, which are involved in angiogenesis and adipogenesis, via a paracrine effect.

Ginsenoside Rg1 Accelerates Paracrine Activity and Adipogenic Differentiation of Human Breast Adipose-Derived Stem Cells in a Dose-Dependent Manner In Vitro

“…From this perspective, several techniques have been developed to optimize the efficacy of ASCs in fat transplantation, such as drug stimulation, physical treatment, or gene modification 7 , 13 , 31 , 32 . By contrast, Yuan et al report that most transplanted ASCs die during the 1st week after transplantation and suggest that angiogenic growth factors (e.g., VEGF, EGF) secreted by ASCs increase the neovascularization density of fat grafts 33 . Besides the secretion of paracrine factors, our recent findings indicate that a portion of retained hbASCs in fat grafts differentiate into vascular endothelial cells, becoming an extra cell source for new vessel formation, and that CXCR4-modified ASCs enhance the neovascularization density of fat grafts 34 .…”

“…This phenomenon suggests that immune activity contributes to angiogenesis, consistent with the theory of tumor angiogenesis, and that immunologic factors secreted by ASCs (e.g., TGF-b1 35 , IL-10) are responsible for the enhanced density of neovascularization in fat grafts 36 . We previously observed adipogenic differentiation and increased paracrine activity of ASCs in adipose grafts, suggesting both above-mentioned regeneration modes play important roles in ASC-assisted fat grafting, and that graft take is enhanced when ASCs are pretreated with certain drugs or genetic modifications 22,33 . We suspect that the variable efficacy of ASCs in fat grafting results from different optimization methods between studies, which may induce different fat graft regeneration modes.…”

“…Besides the secretion of paracrine factors, our recent findings indicate that a portion of retained hbASCs in fat grafts differentiate into vascular endothelial cells, becoming an extra cell source for new vessel formation, and that CXCR4-modified ASCs enhance the neovascularization density of fat grafts 34 . Neovascularization in the early stage after transplantation is critical to long-term fat retention and is associated with an increased number of inflammatory cells 33 . This phenomenon suggests that immune activity contributes to angiogenesis, consistent with the theory of tumor angiogenesis, and that immunologic factors secreted by ASCs (e.g., TGF-β1 35 , IL-10) are responsible for the enhanced density of neovascularization in fat grafts 36 .…”

Adjusting the stiffness of a cell-free hydrogel system based on tissue-specific extracellular matrix to optimize adipose tissue regeneration

“…Indeed, angiogenesis and network formation are regulated by stiffness [ 45 , 46 ]. Early-stage angiogenesis in adipose tissue is very important for regeneration after grafting [ 47 , 48 ]. However, fine vascularization and sufficient supply of seed cells did not lead to better adipose regeneration in our current study.…”

Deciphering the Emerging Roles of Adipocytes and Adipose-Derived Stem Cells in Fat Transplantation

“…Interestingly, Yuan et al proposed that early vascularization of ADSCs mainly relies on secretion to produce various vascularization factors, rather than differentiation to produce functional cells 77 . As also confirmed by Yi et.al., the role of exogenous ADSCs in free fat transplantation may not directly participate in angiogenesis and adipogenesis but may promote the survival ratio of the graft-resident interstitial cells, which are involved in angiogenesis and adipogenesis, via a paracrine effect 78 . Importantly, ADSCs also participate in enhancing neovascularization via the autocrine and paracrine effect of angiogenic cytokines, including VEGF, bFGF, EGF, IGF-1, HGF, PDGF, and thereby increase the survival rate of fat grafts.…”