Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells
Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells
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DOI：
10.1182/blood-2004-03-1051
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Gurtner, GC
中科院分区：
文献类型：
--
作者：
Tepper, OM;Capla, JM;Gurtner, GC
缺血是已知的血管生长刺激。骨髓（BM）来源的内皮祖细胞（EPCs）被认为有助于新血管的生长，但这种贡献的机制尚不清楚。为了阐明BM细胞如何能够形成新血管，在致死性照射的小鼠中开发了一种新的软组织缺血的鼠模型，其中BM由tie 2/lacZ或ROSA/绿色荧光蛋白（GFP）小鼠重建（n = 24）。骨髓来源的EPCs在72小时内被募集到缺血组织，募集的程度与组织缺血的程度成正比。在第7天，血管内皮生长因子（VEGF）（2.5倍）和循环VEGF受体-2/CD11（-）（flk-1（+）/CD 11（-））细胞（18倍）水平持续升高，这与缺血组织中BM来源的EPCs数量增加相关。细胞最初位于血管外的增殖集群。到第14天，这些簇合并成血管索，到第21天成为功能性血管。来自健康志愿者（n = 10）的人EPCs的体外检查证实，在缺氧条件下，EPC增殖、粘附和趋化性都被显著刺激。我们的结论是，BM衍生的细胞产生新的血管通过本地化的招聘，增殖和分化的循环细胞在一系列的事件显着不同于现有的血管生成的范例。(C)2005年美国血液学会。
Ischemia is a known stimulus for vascular growth. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are believed to contribute to new blood vessel growth, but the mechanism for this contribution is unknown. To elucidate how BM cells are able to form new blood vessels, a novel murine model of soft tissue ischemia was developed in lethally irradiated mice with BM reconstituted from either tie2/lacZ or ROSA/green fluorescent protein (GFP) mice (n = 24). BM-derived EPCs were recruited to ischemic tissue within 72 hours, and the extent of recruitment was directly proportional to the degree of tissue ischemia. At 7 days, there were persistently elevated levels of vascular endothelial growth factor (VEGF) (2.5-fold) and circulating VEGF receptor-2/CD11(-) (flk-1(+)/CD11(-)) cells (18-fold) which correlated with increased numbers of BM-derived EPCs within ischemic tissue. The cells were initially located extravascularly as proliferative clusters. By day 14, these clusters coalesced into vascular cords, which became functional vessels by day 21. In vitro examination of human EPCs from healthy volunteers (n = 10) confirmed that EPC proliferation, adhesion, and chemotaxis were all significantly stimulated in hypoxic conditions. We conclude that BM-derived cells produce new blood vessels via localized recruitment, proliferation, and differentiation of circulating cells in a sequence of events markedly different from existing paradigms of angiogenesis. (C) 2005 by The American Society of Hematology.