Effectiveness of Bone Marrow Stromal Cell Sheets in Maintaining Random-Pattern Skin Flaps in an Experimental Animal Model

BACKGROUND: Bone marrow stromal cells can be applied therapeutically to enhance angiogenesis; however, the use of bone marrow stromal cell suspensions reduces efficiency because of low-level attachment. The authors hypothesized that bone marrow stromal cell sheets would facilitate cell fixation, thus enhancing angiogenesis. The authors investigated flap survival area and enhancement of angiogenic factors in a rat random-pattern skin flap model after application of bone marrow stromal cell sheets. METHODS: Bone marrow stromal cell sheets (prepared from 7-week-old rat femurs) were cultured under four different hypoxic conditions. Sheets with the highest angiogenic potential, determined by an in vitro pilot study, were injected into subcutaneous layers of the rat dorsum (bone marrow stromal cell sheet group). A control group (phosphate-buffered saline only) was included. On day 2 after injection, caudally based random-pattern skin flaps (12 × 3 cm) were elevated. On day 7 after elevation, surviving skin flap areas were measured. Skin samples were harvested from each flap and gene expression levels of vascular endothelial growth factor and basic fibroblast growth factor were measured by quantitative real-time polymerase chain reaction. RESULTS: Skin flap survival area (71.6 ± 2.3 percent versus 51.5 ± 3.3 percent) and levels of vascular endothelial growth factor and basic fibroblast growth factor were significantly higher in the bone marrow stromal cell sheet group than in the control group (p < 0.05). CONCLUSIONS: Implantation of bone marrow stromal cell sheets increased the survival area of random-pattern skin flaps. Expression of angiogenic factors may have contributed to the increased flap survival.