Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice
Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice
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DOI：
10.1096/fj.06-6884com
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
--
作者：
Tanaka, Kimie;Sata, Masataka;Nagai, Ryozo
最近的证据表明，骨髓来源的细胞可能有助于血管损伤后的修复和损伤的形成。在大多数研究中，通过将外源细胞移植到受辐射影响的骨髓中来追踪骨髓来源的细胞。在生理条件下，内源性循环祖细胞是否真的参与动脉重塑仍有待确定。在这里，我们建立了一种异生动物模型，在该模型中，两只小鼠被连接到皮下，没有任何血管吻合。当野生型小鼠与在所有组织中表达绿色荧光蛋白(GFP)的转基因小鼠连接时，不仅在野生型小鼠的外周血中检测到GFP阳性细胞，而且在骨髓中也检测到GFP阳性细胞。野生型小鼠的股动脉通过插入一根大钢丝进行机械损伤。4wk时可见新生内膜增生，主要由α-平滑肌肌动蛋白阳性细胞组成。GFP阳性细胞主要见于损伤动脉的新生内膜(14.8±4.5%)和中膜(31.1±8.8%)。一些GFP阳性细胞表达α-平滑肌肌动蛋白或内皮细胞标记物。这些结果表明，即使在未受照射的小鼠中，循环中的祖细胞也参与了机械血管损伤后的再内皮化和新生内膜的形成。
Recent evidence suggests that bone marrow-derived cells may contribute to repair and lesion formation following vascular injury. In most studies, bone marrow- derived cells were tracked by transplanting exogenous cells into bone marrow that had been compromised by irradiation. It remains to be determined whether endogenous circulating progenitors actually contribute to arterial remodeling under physiological conditions. Here, we established a parabiotic model in which two mice were conjoined subcutaneously without any vascular anastomosis. When wild-type mice were joined with transgenic mice that expressed green fluorescent protein (GFP) in all tissues, GFP-positive cells were detected not only in the peripheral blood but also in the bone marrow of the wild-type mice. The femoral arteries of the wild-type mice were mechanically injured by insertion of a large wire. At 4 wk, there was neointima hyperplasia that mainly consisted of alpha-smooth muscle actin-positive cells. GFP-positive cells were readily detected in the neointima (14.8 +/- 4.5%) and media (31.1 +/- 8.8%) of the injured artery. Some GFP-positive cells expressed alpha-smooth muscle actin or an endothelial cell marker. These results indicate that circulating progenitors contribute to re-endothelialization and neointimal formation after mechanical vascular injury even in nonirradiated mice.