Neointima Formation

Abstract

Where do intimal smooth muscle cells (SMCs) come from? For many years, the idea that intimal SMCs originated from the underlying media went unchallenged.1 Then, reports2,3 began to appear that up to half of the SMCs in the intima of atherosclerotic plaques and injured arteries arose from circulating progenitor cells of bone marrow origin. This new view of intimal SMC formation was potentially important because it raised the possibility of a new class of therapeutic targets for intervention in the process of restenosis based on a bone marrow derivation of intimal SMCs. However, as other laboratories began to follow up on these intriguing initial reports, a long-term contribution of bone marrow–derived cells to intimal tissue became less tenable.4,5 In this issue of A rterio s clerosis , T hrombosis, and Vascular Biology , a careful and detailed study by Daniel et al6 seems to leave little or no room for a role of bone marrow–derived cells as progenitors for the intimal SMCs and endothelial cells that are stable residents of a mature neointima that forms after acute vascular injury. See accompanying article on page 1890 Daniel et al6 transplanted bone marrow from enhanced green fluorescent protein (EGFP)–positive (EGFPpos) mice into lethally irradiated wild-type C57Bl/6 mice, allowed 12 weeks for stable engraftment, performed wire injury to the femoral artery, and then recovered injured tissues from 3 days to 16 weeks after injury. The extended time course is important because most studies of neointimal formation in this model usually stop at 4 weeks (occasionally at 8 weeks) after vascular injury. Daniel et al observed rapid accumulation of EGFPpos cells in neointimal tissue that peaked in the first 2 weeks after injury and accounted for up to 68% of the total cells in the neointima. However, …