Role of Adipose Derived Stem Cells in Skin Flap Survival in a Rat Model (Experimental Study)

Abstract

Skin flap necrosis represents a great challenge in plastic and reconstructive surgery. The augmentation of skin flap survival has been of great concern for plastic surgeons. Different techniques have been employed to enhance angiogenesis within areas of ischaemia. The most effective method of increasing survival area is the surgical delay. However, the delay procedure requires repeated operations. The pharmacological manipulation mimics the surgical delay, and thereby increases the skin blood flow. However, the effects of drugs are usually transient and unstable. Angiogenic growth factors such as VEGF, bFGF and TGF-β, have been shown to be effective agents in reducing skin flap necrosis. However, their effects are limited by their short duration of action and the need for high doses. Recently, the rapid development of cell biology has helped to highlight the ability of adult stem cells, especially bone marrow-derived stem cells and adipose-derived stem cells to promote neovascularization. Adipose derived stem cells were first described in 2001 by Zuk et al. ASCs are preferable compared with bone marrow derived stem cells because of their presence in abundant amount and the ease of harvesting. Therapeutic effects of ASCs are attributed to two distinct mechanisms; paracrine pathway and cell differentiation. The paracrine pathway exists when the administered ASCs produce angiogenic factors such as VEGF, PDGF and bFGF that improve neovascularization. ASCs differentiate into endothelial cells, thereby augmenting blood supply. In our research, we studied the role of adipose derived stem cells in random skin flap survival in a rat model and the optimal timing for administration of ASCs. The study included four main groups according to the timing of ASCs application; Group A at the time of flap elevation, Group B two days prior to flap elevation, Group C seven days prior to flap elevation and Group D is the control group. Skin flap survival was evaluated on the seventh postoperative day through: percentage of flap survival, capillary density and VEGF expression. ASCs led to a statistically significant increase in skin flap viability when administered simultaneously with flap elevation or two days prior to flap elevation. This went along with the significant increase of capillary density and VEGF expression. However, the ASCs had no effect on flap survival when injected one week prior to flap elevation. In conclusion, from this study we demonstrate that the viability of random pattern skin flap can be enhanced by local ASCs administration simultaneously with flap elevation or two days prior to flap elevation. Their beneficial effect is attributed to paracrine secretion of growth factors such as VEGF which enhanced the skin flap vascularity. The angiogenic effect of ASCs can be maximized when the ASCs are injected at the time of flap elevation.