Improved wound healing of postischemic cutaneous flaps with the use of bone marrow-derived stem cells

Abstract

Objectives/hypothesis: To determine if the intravascular delivery of mesenchymal stem cells improves wound healing and blood perfusion to postischemic cutaneous flap tissues.

Study design: Randomized controlled study.

Methods: A murine model of a cutaneous flap was created based on the inferior epigastric vessels. Mice (n = 14) underwent 3.5 hours of ischemia followed by reperfusion. Bone marrow stromal cells (BMSCs) 1 × 10(6) were injected intravenously. Wound healing was then assessed measuring percent flap necrosis, flap perfusion, and tensile strength of the flap after a period of 14 days. Localization of BMSCs was determined with radiolabeled and fluorescent labeled BMSCs.

Results: Postischemic cutaneous flap tissues treated with BMSCs demonstrated significantly less necrosis than control flaps (P <0.01). Beginning on postoperative day 5, BMSC-treated flaps demonstrated greater blood perfusion than untreated flaps (P <0.01). Tensile strength of BMSC-treated cutaneous flaps was significantly higher (P <0.01), with a mean strength of 283.4 ± 28.4 N/m than control flaps with a mean of 122.4 ± 23.5 N/m. Radiolabeled BMSCs localized to postischemic flaps compared to untreated tissues (P = 0.001). Fluorescent microscopy revealed incorporation of BMSCs into endothelial and epithelial tissues of postischemic flaps.

Conclusions: This study demonstrates that the intravascular delivery of BMSCs increases wound healing and promotes flap survival following ischemia-reperfusion injury of cutaneous tissue flaps.

Keywords: Bone marrow stromal cells; Level of Evidence: NA; cutaneous flaps; free tissue transfer; ischemia; stem cells; wound healing.