There is an accumulating body of evidence that in the adult bone marrow there are somatic stem cells which can differentiate into various lineages, including vascular endothelial cells 1, 2. Recently, it was demonstrated that Flk1-positive cells derived from embryonic stem cells can differentiate into both endothelial cells and smooth-muscle cells, reproducing the vascular organization process 3. This has aroused enthusiasm for the potential use of somatic stem cells for tissue engineering of the vascular system; however, it remains to be determined whether the vascular progenitor cells contribute to the growth of smooth-muscle cells observed in vascular lesions, such as atherosclerosis, post-angioplasty restenosis and transplant-related vasculopathy 4.

Thus, to evaluate the involvement of vascular progenitor cells in the pathogenesis of vascular lesions, we investigated the origin of neointimal cells by performing heterotopic cardiac transplantation between wild-type mice and ROSA26 mice (LacZ mice), which express the marker gene LacZ, ubiquitously and constitutively 5. At thirty days after transplantation, the allografts were collected and stained with X-gal to detect the cells derived from LacZ mice. The lumens of large pericardial coronary arteries as well as their smaller branches were narrowed by neointimal hyperplasia (Fig. 1). In the wild-type allograft transplanted into a LacZ mouse, most of the neointimal cells expressed LacZ (86.2±3.2%), whereas only a few medial cells (10.2±6.2%) were positive (Fig. 1a). In contrast, when the heart from a LacZ mouse was transplanted into a wild-type mouse, few neointimal cells (2.3±1.1%) were positive for LacZ whereas most of the medial cells (65.3±12.4%) expressed LacZ. Immunohistochemical analysis revealed that the neointima as well as the media was exclusively composed of α-smooth-muscle actin-positive cells (Fig. 1b). Moreover, in situ hybridization of the allografts from female to male mice revealed that most of the neointimal cells corresponded to cells from the recipients (Fig. 1c). Taken together, these results indicate that the majority of the neointimal cells derived from the recipient cells.