Time-Course Analysis on the Differentiation of Bone Marrow-Derived Progenitor Cells Into Smooth Muscle Cells During Neointima Formation
Time-Course Analysis on the Differentiation of Bone Marrow-Derived Progenitor Cells Into Smooth Muscle Cells During Neointima Formation
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DOI：
10.1161/atvbaha.110.209692
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发表时间：
2010-10-01
影响因子：
8.7
通讯作者：
Sedding, Daniel G.
中科院分区：
文献类型：
--
作者：
Daniel, Jan-Marcus;Bielenberg, Wiebke;Sedding, Daniel G.
骨髓来源的祖细胞已被认为有助于新生内膜形成，但其积累和分化为血管细胞的时间进程和程度，最重要的是，骨髓来源的祖细胞对血管病变的长期贡献仍然不确定。方法和结果-在移植了来自表达增强型绿色荧光蛋白的转基因小鼠的骨髓的嵌合C57 BL/6小鼠上进行线诱导的股动脉损伤，并在扩张后3天、1、2、3、4、6和16周收获血管（每个时间点n = 8只动物）。使用高分辨率显微镜，我们意外地发现，平滑肌细胞或内皮细胞标记物的表达在增强的绿色荧光蛋白阳性细胞是一个非常罕见的事件。事实上，在急性炎症反应期间积累的大多数增强的绿色荧光蛋白阳性细胞被鉴定为单核细胞/巨噬细胞，并且它们的数量在稍后的时间点下降。相反，在外膜中检测到大量高度增殖的干细胞抗原-1和CD 34（+），但增强的绿色荧光蛋白阴性，因此是局部来源的细胞。结论-这些数据提供了证据，骨髓来源的祖细胞分化成平滑肌细胞或内皮细胞谱系似乎是一个非常罕见的事件。此外，骨髓源性细胞对新生内膜细胞区室的贡献仅限于炎症反应的短暂时期。（Arterioscler Thromb Vasc Biol.2010;30：1890-1896.）
Bone marrow-derived progenitor cells have been implicated to contribute to neointima formation, but the time course and extent of their accumulation and differentiation into vascular cells and, most importantly, the long-term contribution of bone marrow-derived progenitor cells to the vascular lesion remain undefined. Methods and Results-Wire-induced injury of the femoral artery was performed on chimeric C57BL/6 mice transplanted with bone marrow from transgenic mice expressing enhanced green fluorescence protein, and vessels were harvested at 3 days, 1, 2, 3, 4, 6, and 16 weeks after dilatation (n = 8 animals per time point). Using high-resolution microscopy, we unexpectedly found that the expression of smooth muscle cell or endothelial cell markers in enhanced green fluorescence protein positive cells was a very rare event. Indeed, most of the enhanced green fluorescence protein positive cells that accumulated during the acute inflammatory response were identified as monocytes/macrophages, and their number declined at later time points. In contrast, a substantial fraction of highly proliferative stem cell antigen-1 and CD34(+) but enhanced green fluorescence protein negative and thus locally derived cells were detected in the adventitia. Conclusion-These data provide evidence that the differentiation of bone marrow-derived progenitor cells into smooth muscle cell or endothelial cell lineages seems to be an exceedingly rare event. Moreover, the contribution of bone marrow-derived cells to the cellular compartment of the neointima is limited to a transient period of the inflammatory response. (Arterioscler Thromb Vasc Biol. 2010;30:1890-1896.)