Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Circulation. 2010 Nov 16;122(20):2048-57. doi: 10.1161/CIRCULATIONAHA.110.965202. Epub 2010 Nov 1.
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.
有人提出骨髓来源的细胞浸润到新生内膜，在那里分化为平滑肌（SM）细胞；然而，技术限制阻碍了对骨髓源性“SM 细胞样”细胞谱系的明确鉴定。
使用针对明确的 SM 细胞谱系标志物 SM 肌球蛋白重链（SM-MHC）的特异性抗体，以及由 SM-MHC 或 SM α-肌动蛋白的调控程序驱动报告基因的小鼠系，我们证明尽管一些骨髓来源的细胞在钢丝损伤诱导的新生内膜中表达 SM α-肌动蛋白，但这些细胞不表达 SM-MHC，即使在损伤后 30 周也是如此。同样，在载脂蛋白 E（-/-）小鼠的血管病变或心脏移植血管病模型中也未发现 SM-MHC（+）骨髓源性细胞。相反，大多数骨髓源性 SM α-肌动蛋白（+）细胞也为 CD115（+）CD11b（+）F4/80（+）Ly-6C（+），这是炎症单核细胞的表面表型。此外，在损伤的动脉中，转导的 CD11b（+）Ly-6C（+）骨髓细胞表达 SM α-肌动蛋白。在富含骨髓源性 SM α-肌动蛋白（+）细胞的新生内膜亚区中，炎症相关基因的表达明显高于其他区域。
似乎骨髓源性 SM α-肌动蛋白（+）细胞来源于单核/巨噬细胞谱系，并参与血管重塑。这些细胞极不可能获得明确的 SM 细胞谱系。
