Centre for Research in Vascular Biology, Biosciences Institute, University College Cork, Cork, Ireland.
FASEB J. 2010 Jan;24(1):81-92. doi: 10.1096/fj.09-132225. Epub 2009 Sep 10.
Smooth muscle cells play a major role in numerous vascular diseases that contribute to remodeling, repair after injury, and arteriogenesis, and the source of these cells is thought to lie within the vessel wall and the circulating blood. Currently, the precise origin and mechanism of differentiation of extravascular smooth muscle progenitor cells (SPCs) is unclear. We show here that the CX(3)CR1 mononuclear cell population of murine bone marrow provides a source of SPCs that contributes to smooth muscle cells within the neointimal plaque after vascular injury. Moreover, CX(3)CR1-fractalkine (FKN) interaction in vivo is essential for smooth muscle cell differentiation of bone marrow-derived progenitor cells at the vessel wall level. Functional competence of bone marrow-derived CX(3)CR1 positive cells to interact with FKN is also crucial in part for neointima formation following vascular injury. Finally, in a pure preparation of bone marrow-derived CX(3)CR1 positive cells, we show that in vitro smooth muscle cell differentiation increases markedly in the presence of FKN. Our data highlight a novel functional relationship between the myeloid and vascular systems and in the context of vascular injury and repair underscores a key chemokine-receptor pathway that may regulate cell fate when smooth muscle cell differentiation is required.
平滑肌细胞在许多血管疾病中起着重要作用，这些疾病导致血管重塑、损伤后的修复和动脉生成，而这些细胞的来源被认为存在于血管壁和循环血液中。目前，血管外平滑肌祖细胞（SPC）的确切起源和分化机制尚不清楚。我们在这里表明，骨髓中的 CX(3)CR1 单核细胞群提供了 SPC 的来源，这些 SPC 有助于血管损伤后新生内膜斑块中的平滑肌细胞。此外，体内的 CX(3)CR1- fractalkine（FKN）相互作用对于血管壁水平的骨髓源性祖细胞的平滑肌细胞分化是必不可少的。骨髓源性 CX(3)CR1 阳性细胞与 FKN 相互作用的功能能力对于血管损伤后的新内膜形成也至关重要。最后，在骨髓源性 CX(3)CR1 阳性细胞的纯制剂中，我们表明在 FKN 存在的情况下，体外平滑肌细胞分化显著增加。我们的数据突出了骨髓细胞和血管系统之间的新的功能关系，并在血管损伤和修复的背景下强调了一种关键的趋化因子-受体途径，当需要平滑肌细胞分化时，该途径可能调节细胞命运。
