Background: Virtually all aspects of plastic surgery rely on new blood vessel growth, including flaps, grafts, distraction osteogenesis, and wound healing. For decades, plastic surgery as well as medicine in general has advanced under the pretense that blood vessel growth in the adult is restricted to the sprouting of pre-existing, mature blood vessels (angiogenesis). However, we recently isolated endothelial progenitor cells (EPCs) from humans, thereby discovering a new concept of adult “vasculogenesis” in which EPCs differentiate in situ. These cells have been shown to participate in neovascularization under variuos conditions, but their relative contribution is still unknown. This study set out to quantify the contribution of EPCs to newly formed vascular structures in vivo.

Methods: In order to track the recruitment of EPCs from the bone marrow (BM) and their incorporation into new vessels, we prepared mice (n=28) in which lacZ expression is limited to BM-derived EPCs. BM cells from tie2/lacZ transgenic mice (lacZ expression is regulated by an endothelial-specific tie-2 promoter) were transplanted to FVB/N mice that had their endogenous bone marrow destroyed through irradiation. Following reconstitution of the BM, two independent assays of new blood vessel growth were employed; MATRIGEL and corneal neovascularization. Since the expression of lacZ in our model is restricted to BM-derived EPCs, we then determined which new vessels had originated from EPCs by identifying lacZ expression through x-gal staining and immunohistochemistry (IHC).

Results: EPCs made a significant contribution to blood vessel formation in both assays of neovascularization. The MATRIGEL plug assay identified 5.7±1.2% and 26.5±0.9% of endothelial cells originated from EPCs using X-gal staining and IHC, respectively. Similarly, EPCs comprised of 5.0±2.4 %(x-gal) and 17.7±3.6% (IHC) of the endothelial cells in corneal neovascularization

Conclusions: Our findings indicate that EPCs make a significant contribution to new blood vessels or capillaries in vivo, and thus have important implications for a number of plastic surgery procedures. Further investigation of EPCs may offer novel explanations for impaired blood vessel growth associated with certain patients groups (i.e. diabetics and smokers) as well as offer potential therapeutic benefit through methods of stem cell transplantation.