Intra-arterial injection of human adipose-derived stem cells improves viability of the random component of axial skin flaps in nude mice

Abstract

Skin flap necrosis is a common postoperative complication in reconstructive surgery. Recent evidence suggests that subcutaneously injected adipose-derived stem cells (ASCs) increase the viability of random skin flaps. Here, we examined whether intra-arterial human ASC administration could improve random component survival of axial skin flaps in nude mice. Human ASCs isolated from a healthy volunteer by liposuction were injected into nude mice through the right femoral artery at a low (1 × 103 cells), medium (1 × 104 cells), or high (1 × 105 cells) dose. After ASC infusion, right superficial inferior epigastric vessels were ligated to create unipedicled superficial inferior epigastric artery (SIEA) flap with random extension. Flap survival was higher in mice from all three ASC-treated groups, and particularly the medium-dose group was 30% better, than in the control group. Histological examination demonstrated a significantly higher vascular density in the axial skin flap in nude mice treated with the medium ASC dose than in control mice. PKH26-labeled ASCs were identified in skin flaps of ASC-treated mice; some endothelial cells exhibited positive staining for human HLA-A. Compared to the control group, mice in ASC-treated groups had higher vascular endothelial growth factor levels and lower tumor necrosis factor α, interferon γ, and interleukin-6 levels. Intra-arterial human ASC administration increased the survival of axial skin flaps by attenuating inflammatory reactions and enhancing neovascularization. Intra-arterial ASC administration might yield a higher rate of these cells and of engraftment in the skin flaps. This approach may have a therapeutic role in increasing flap survival.