小鼠外膜Sca-1 + CD45 +祖细胞的血管生成特性：动脉粥样硬化脉管血管的潜在来源。,Scientific Reports

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小鼠外膜Sca-1 + CD45 +祖细胞的血管生成特性：动脉粥样硬化脉管血管的潜在来源。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-05-13 , DOI: 10.1038/s41598-019-43765-8
Deborah Toledo-Flores ₁ , Anna Williamson _{1,

2} , Nisha Schwarz ₁ , Sanuja Fernando _{1,

2} , Catherine Dimasi ₁ , Tyra A Witt ₃ , Thao M Nguyen _{1,

2} , Amrutesh S Puranik ₃ , Colin D Chue ₃ , Sinny Delacroix _{2,

3} , Daniel B Spoon ₃ , Claudine S Bonder _{2,

4} , Christina A Bursill _{1,

2} , Belinda A Di Bartolo _{1,

2} , Stephen J Nicholls _{1,

2} , Robert D Simari _{3,

5} , Peter J Psaltis _{1,

2,

3}

Affiliation

脉管血管的细胞起源不清楚，可能涉及循环或局部祖细胞。我们先前发现鼠主动脉外膜含有产生巨噬细胞的Sca-1 + CD45 +祖细胞。在这里，我们调查了它们是否也具有血管生成作用。在C57BL / 6小鼠的主动脉中，Sca-1 + CD45 +细胞定位于外膜，并且缺乏内皮标志物的表面表达（对于CD31，CD144，TIE-2，<1％）。相反，它们确实在动脉粥样硬化的ApoE-/-主动脉中显示了CD31，CD144，TIE-2和VEGFR2的表达。尽管来自C57BL / 6主动脉的Sca-1 + CD45 +细胞不表达CD31，但它们在内皮分化培养基中形成CD31 +集落，并在基质胶中产生了互连的血管样索，其中既包含内皮细胞，又包含少量的巨噬细胞，位于分支点。在无缺血的后肢模型中，主动脉Sca-1 + CD45 +细胞的转移产生了内皮细胞和新生血管，与无细胞对照组相比，灌注增加了50％。同样，在动脉粥样硬化饮食后，将它们注射到ApoE-/-小鼠的颈动脉外膜中可产生供体来源的外膜和外膜周围微血管，提示新形成的血管脉管。这些发现表明，外膜Sca-1 + CD45 +细胞除了其巨噬细胞祖细胞的含量外，还具有血管生成作用，并且可能是动脉粥样硬化形成过程中血管脉管的来源。将它们注射到ApoE-/-小鼠的颈动脉外膜后，经动脉粥样硬化饮食后产生了供体来源的外膜和外膜周围微血管，提示新形成的血管脉管。这些发现表明，外膜Sca-1 + CD45 +细胞除了其巨噬细胞祖细胞的含量外，还具有血管生成作用，并且可能是动脉粥样硬化形成过程中血管脉管的来源。将它们注射到ApoE-/-小鼠的颈动脉外膜后，经动脉粥样硬化饮食后产生了供体来源的外膜和外膜周围微血管，提示新形成的血管脉管。这些发现表明，外膜Sca-1 + CD45 +细胞除了其巨噬细胞祖细胞的含量外，还具有血管生成作用，并且可能是动脉粥样硬化形成过程中血管脉管的来源。

"点击查看英文标题和摘要"

Vasculogenic properties of adventitial Sca-1+CD45+ progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis.

The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1+CD45+ progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1+CD45+ cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE-/- aortas. Although Sca-1+CD45+ cells from C57BL/6 aorta did not express CD31, they formed CD31+ colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1+CD45+ cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE-/- mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1+CD45+ cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

更新日期：2019-05-16

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