Circulating progenitors contribute to vascular repair and lesion formation
Masataka Sata, MD, Ph.D
University of Tokyo Graduate School of Medicine, Tokyo, Japan
Accumulating evidence suggests that circulating progenitors potentially contribute to vascular
healing and remodeling under physiological and pathological conditions. Although there is growing
enthusiasm for therapeutic and diagnostic application of circulating progenitors, there are concerns
that transplanted precursors or bone marrow-derived cells may participate in the pathogenesis of
unfavorable diseases such as cancer, retinopathy, and atherosclerosis. Thus, it is warranted to
clarify the molecular signaling that regulates the fate of circulating vascular progenitors. We
investigated potential contribution of circulating blood cells in various types of vascular remodeling. We
also studied the mechanical and humoral factors that recruit circulating progenitors to vascular lesions.
We examined the vascular lesions in models of transplant arteriosclerosis, post-PCI restenosis, and
hyperlipidemia-induced atherosclerosis after bone marrow (BM) transplantation from LacZ-mice or
GFP-mice to wild-type mice. Peripheral blood mononuclear cells (PBMNCs) were collected from animals or
patients and cultured in the presence of various cytokines. A significant amount of α-actin-positive cells in
the vascular lesions were derived from BM. BM-derived cells also participated in re-endothelialization of
the luminal side and neovascularization in the adventitia. Contribution of BM cells to neointimal hyperplasia
depends on the type of injury models. PBMNCs differentiated into SMC-like cells or endothelial-like cells
in vitro depending on the cytokines in the medium. In contrast to media-derived SMCs, the
PBMNCs-derived SMC-like cells expressed abundant MMP-9 and little collagen. Coronary risk factors and
angiotensin receptor blockers significantly influenced the number of circulating PBMNCs that could
differentiate into SMC-like cells or endothelial-like cells.
Our findings suggest that BM cells can give rise to vascular progenitor cells that home at the damaged
vessels and differentiate into SMC-like cells or endothelial-like cells, thereby contributing to vascular repair,
remodeling, and lesion formation. Tissue renin-angiotensin system appears to play an important role in
mobilization, homing, differentiation and proliferation of circulating vascular progenitor cells.