Abstract

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.

Highlights

  • Autologous fat transfer (AFT; 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]

  • A titration experiment was performed to analyse the effect of different electrical stimulation parameters on the viability and detachment of the Adipose-derived stem cells (ASC) after 72 hours of continuous stimulation

  • Representative images of the control and electrical stimulation (ES)-treated chorioallantoic membrane (CAM), including their analysis, can be found in Supplementary Fig. S1. This proof-of-concept study demonstrates that ES of ASC improves in vitro and in vivo parameters of angiogenesis

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Summary

Introduction

Autologous fat transfer (AFT; 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]. 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]. A major advantage of ES is that by influencing the secretion profile of stimulated cells it can induce autologous cells to secrete a myriad of important factors, in contrast of having to inject specific exogenous factors[30] In light of these findings, we hypothesized that ES would enhance the secretion of paracrine angiogenic factors by ASC, leading to increased angiogenesis. In this study we aim to determine whether ES of ASC can stimulate in vivo parameters of angiogenesis

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