Bone Marrow-Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages

Background-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. Methods and Results-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 alpha-actin, we demonstrated that although some bone marrow-derived cells express SM alpha-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 alpha-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 alpha-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM alpha-actin(+) cells than in other regions. Conclusions-It appears that bone marrow-derived SM alpha-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. (Circulation. 2010; 122: 2048-2057.)