Electrical stimulation promotes the angiogenic potential of adipose-derived stem cells (original) (raw)

Autologous fat transfer (AFT) is limited by post-operative volume loss due to ischemia-induced cell death in the fat graft. Previous studies have demonstrated that electrical stimulation (ES) promotes angiogenesis in a variety of tissues and cell types. In this study we investigated the effects of ES on the angiogenic potential of adipose-derived stem cells (ASC), important progenitor cells in fat grafts with proven angiogenic potential. Cultured human ASC were electrically stimulated for 72 hours after which the medium of stimulated (ES) and non-stimulated (control) ASC was analysed for angiogenesis-related proteins by protein array and ELISA. The functional effect of ES on angiogenesis was then assessed in vitro and in vivo. Nine angiogenesis-related proteins were detected in the medium of electrically (non-)stimulated ASC and were quantified by ELISA. The pro-angiogenic proteins VEGF and MCP-1 were significantly increased following ES compared to controls, while the anti-angiogenic factor Serpin E1/PAI-1 was significantly decreased. Despite increased levels of anti-angiogenic TSP-1 and TIMP-1, medium of ES-treated ASC significantly increased vessel density, total vessel network length and branching points in chorio-allantoic membrane assays. In conclusion, our proof-of-concept study showed that ES increased the angiogenic potential of ASC both in vitro and in vivo. Autologous fat transfer (AFT; also called fat grafting or lipofilling) is a widely used reconstructive and aesthetic procedure, wherein fat is harvested as an injectable filler to augment or reconstruct tissue in all regions of the body 1. Currently, post-operative volume loss, described to be ranging from 40 to 80% of the initial graft volume 2-4 , is a significant limitation of AFT, and often requires additional grafting procedures. A lack of blood flow through the graft necessitates the transplanted cells to fully rely on the diffusion of oxygen and nutrients from surrounding tissue for their survival 5. In an experimental mouse model, Kato et al. 6 have shown that only adipocytes in the outermost layer of the transferred fat tissue survive the first week post-operative, while adipocytes present inwards of the diffusion limit of approximately 300 µm quickly die. Numerous studies have focused on revascularization of the graft by stimulating angiogenesis in order to improve graft survival and maximize the retained graft volume. Approaches primarily focused on increasing the vascularization of the recipient site pre-and post-operatively 7,8 or on modifying the pro-angiogenic potential of the adipose graft itself by adding single growth factors (i.e. FGF-2, PDGF and IL-8) 9-11 , platelet-rich plasma 12,13 , by adding regenerative cells from stromal vascular fractions 3,4 or by adding isolated adipose-derived stem cells 14,15. While administration of angiogenic growth factors has been proven to stimulate angiogenesis 16 , clinical implementation is hampered by the short serum half-life and adverse effects associated with continuous administration 17. Others have suggested to enrich fat grafts with a heterogeneous population of regenerative cells, called the stromal vascular fraction, which is normally present in adipose tissue 18,19. This procedure has been dubbed cell-assisted lipotransfer (CAL) 19. However, Peltoniemi et al. 20 , did not find CAL to be superior to non-enriched