Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice.

Recent evidence suggests that bone marrow-derived cells may contribute to repair and lesion formation following vascular injury. In most studies, bone marrow-derived cells were tracked by transplanting exogenous cells into bone marrow that had been compromised by irradiation. It remains to be determined whether endogenous circulating progenitors actually contribute to arterial remodeling under physiological conditions. Here, we established a parabiotic model in which two mice were conjoined subcutaneously without any vascular anastomosis. When wild-type mice were joined with transgenic mice that expressed green fluorescent protein (GFP) in all tissues, GFP-positive cells were detected not only in the peripheral blood but also in the bone marrow of the wild-type mice. The femoral arteries of the wild-type mice were mechanically injured by insertion of a large wire. At 4 wk, there was neointima hyperplasia that mainly consisted of alpha-smooth muscle actin-positive cells. GFP-positive cells were readily detected in the neointima (14.8+/-4.5%) and media (31.1+/-8.8%) of the injured artery. Some GFP-positive cells expressed alpha-smooth muscle actin or an endothelial cell marker. These results indicate that circulating progenitors contribute to re-endothelialization and neointimal formation after mechanical vascular injury even in nonirradiated mice.