Abstract
Exuberant accumulation of smooth muscle cells plays a principal role in the pathogenesis of vascular diseases. It has been assumed that smooth muscle cells derived from the adjacent medial layer migrate, proliferate and synthesize extracellular matrix. Although a lot of effort has been devoted targeting migration and proliferation of medial smooth muscle cells, no effective therapy to prevent occlusive vascular remodeling has been established. Here, we show that bone marrow cells give rise to the majority of smooth muscle cells that contribute to arterial remodeling in models of post-angioplasty restenosis, graft vasculopathy and hyperlipidemia-induced atherosclerosis. Notably, purified hematopoietic stem cells differentiated into smooth muscle cells in vitro and in vivo. Our findings suggest that somatic stem cells contribute to pathological remodeling of remote organs. Our study provides the basis for the development of a new therapeutic strategies for vascular diseases, targeting mobilization, homing, differentiation and proliferation of bone marrow-derived vascular progenitor cells.
