Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity
Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity
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DOI：
10.1152/ajplung.00314.2007
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
Stevens, Troy
中科院分区：
文献类型：
--
作者：
Alvarez, Diego F.;Huang, Lan;Stevens, Troy
内皮祖细胞是从出生后从骨髓、血液以及管道血管的内、外膜中分离出来的。然而，目前尚不清楚是否能从肺微循环中分离出内皮祖细胞。因此，我们试图确定微血管系统是否具有能够新生血管生成的内皮细胞。用单细胞集落形成法分离和筛选大鼠肺动脉(PAEC)和微血管(PMVEC)内皮细胞。大多数(接近60%)的PAEC是完全分化的，而大多数PMVEC(类似于75%)是分裂的，接近50%的单个细胞形成大的集落(>；2000个/克隆)。这些高度增殖的细胞能够重建PMVECs的整个增殖层次，揭示了驻留的微血管内皮祖细胞(RMEPC)的存在。RMEPC表达内皮细胞标志(CD31、CD144、内皮型一氧化氮合酶和von Willenbrand因子)和祖细胞抗原(CD34和CD309)，但不表达白细胞标志CD45。与它们的起源一致，RMEPC与单叶灰树花相互作用，并表现出限制性的屏障特性。体外和体内Matrigel分析表明，RMEPC具有血管生成能力，形成超微结构正常的新生血管。因此，肺微循环中富含内皮祖细胞，在保持功能性内皮细胞微血管特异性的同时，显示出血管生成的能力。
Endothelial progenitor cells (EPCs) have been isolated postnatally from bone marrow, blood, and both the intima and adventitia of conduit vessels. However, it is unknown whether EPCs can be isolated from the lung microcirculation. Thus we sought to determine whether the microvasculature possesses EPCs capable of de novo vasculogenesis. Rat pulmonary artery (PAEC) and microvascular (PMVEC) endothelial cells were isolated and selected by using a single-cell clonogenic assay. Whereas the majority of PAECs (similar to 60%) were fully differentiated, the majority of PMVECs (similar to 75%) divided, with similar to 50% of the single cells giving rise to large colonies (> 2,000 cells/colony). These highly proliferative cells exhibited the capacity to reconstitute the entire proliferative hierarchy of PMVECs, unveiling the existence of resident microvascular endothelial progenitor cells (RMEPCs). RMEPCs expressed endothelial cell markers (CD31, CD144, endothelial nitric oxide synthase, and von Willenbrand factor) and progenitor cell antigens (CD34 and CD309) but did not express the leukocyte marker CD45. Consistent with their origin, RMEPCs interacted with Griffonia simplicifolia and displayed restrictive barrier properties. In vitro and in vivo Matrigel assays revealed that RMEPCs possess vasculogenic capacity, forming ultrastructurally normal de novo vessels. Thus the pulmonary microcirculation is enriched with EPCs that display vasculogenic competence while maintaining functional endothelial microvascular specificity.