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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.