Therapeutic Effects against Tissue Necrosis of Remote Ischemic Preconditioning Combined with Human Adipose-Derived Stem Cells in Random-Pattern Skin Flap Rat Models

Abstract

Introduction

Remote ischemic preconditioning (rIPC) is a preventive strategy against ischemia–reperfusion injury. To reduce ischemia–reperfusion injury of random-pattern skin flaps, we investigated the therapeutic effects of rIPC combined with human adipose-derived stem cells (hADSCs) in a rat model.

Material and Methods

In total, 24 female Sprague Dawley rats were divided into four groups (n = 6 each): control (skin flap only), rIPC, hADSCs, and rIPC + hADSCs. rIPC was performed in the hind limb of the rats over three cycles of 5 min of occlusion and 5 min of reperfusion, using a tourniquet. A rectangular (3 × 9 cm) dorsal skin flap was used. hADSCs (5 × 10⁵ cells/100 µL) labeled with fluorescent dye were transplanted into the normal subcutaneous tissue at the skin flap boundary. After 14 days, the therapeutic effects of rIPC and hADSCs were evaluated via analysis of the necrotic flap area, histopathologic assessment, and immunohistochemistry (von Willebrand Factor (vWF) and CD31).

Results

The necrotic area of the skin flap significantly decreased in the rIPC + hADSCs group (32.75 ± 1.43%) compared with the control (40.60 ± 3.27%, P < 0.01) and rIPC groups (38.84 ± 0.77%, P < 0.05). Dye-labeled hADSCs migrated to the skin flap from the injection site. In the rIPC + hADSCs group, the epithelial tissue and skin appendage had regenerated, and the smooth muscle and subcutaneous fat layers were preserved. Many more vWF- and CD31-positive vessels were observed in the rIPC + hADSCs group compared with the other groups.

Conclusions

The rIPC + hADSCs treatment appeared to reduce skin flap necrosis and activated neovascularization in rats. Therefore, it may be a good strategy for clinical treatment of ischemia–reperfusion injury.

Keywords:

• Skin flap
• ischemic preconditioning
• adipose-derived stem cells
• angiogenesis
• necrosis

This article is referred to by:

An Update in Reconstructive Surgery

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.