It has been proposed that bone marrow–derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow–derived “SM cell–like” cells.

Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SM α-actin, we demonstrated that although some bone marrow–derived cells express SM α-actin in the wire injury–induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC⁺ bone marrow–derived cells were found in vascular lesions in apolipoprotein E^−/−mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow–derived SM α-actin⁺ cells were also CD115⁺CD11b⁺F4/80⁺Ly-6C⁺, which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b⁺Ly-6C⁺ bone marrow cells expressed SM α-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow–derived SM α-actin⁺ cells than in other regions.

It appears that bone marrow–derived SM α-actin⁺ cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage.