Improved survival of ischemic random skin flaps through the use of bone marrow nonhematopoietic stem cells and angiogenic growth factors.

Surgical skin flaps are frequently used in plastic and reconstructive surgery to repair acquired or congenital defects. Necrosis is a common complication associated with these flaps postoperatively as a result of inadequate blood supply. Stem cells are precursor cells with the potential to differentiate into more specialized cells. Angiogenic factors act to direct cellular differentiation and organization to form new vascular elements. Our theory was that the combination of angiogenic growth factors with stem cells derived from the subject preoperatively would augment neovascularization, thereby increasing blood supply to the flap, which may ultimately improve flap survival. In phase I, 40 Lewis rats were randomized into 4 groups of 10. Random dorsal skin flaps were elevated and treated at the same time. The first group was injected with only medium, the second with stem cells, the third with stem cells and angiogenic factors, and the fourth with angiogenic growth factors. Millimetric measurements of flap viability at 7 and 14 days did not show any statistically significant differences between the studied groups. In phase II, 24 rats were also randomized into 4 groups of 6, but this time were treated 1 week before flap elevation. The viability measurements showed an increased rate of viability in the group in which stem cells and the angiogenic factors were administered simultaneously (84.5% +/- 3.2%) as compared with the unmodified control group (62.6% +/- 7.3%) or to the groups in which only precursor cells (60.4% +/- 7.9%) or angiogenic factors (62.3%+/- 10.1%). Increased blood supply brought by these manipulations is believed translated to increased tissue flap survival. Punch biopsies showed that "green fluorescent protein"-labeled precursor cells was noted to form luminal structures in the treated flaps. The vascular cast of all flaps was filled with Mercox plastic resin. After euthanasia, the soft tissues of the harvested flaps were dissolved and the remaining vascular cast was weighted. The weight-based ratio of the vascular composition was determined. The flaps injected with both stem cells and angiogenic factors showed higher values. We conclude that the administration of bone marrow stem cells with angiogenic factors 1 week before flap creation improves the survival of ischemic random skin flaps.