Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals
Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals
复制标题
DOI：
10.1182/blood-2006-08-043471
复制
发表时间：
2007-03-01
期刊：
影响因子：
20.3
通讯作者：
Ingram, David A.
中科院分区：
文献类型：
--
作者：
Yoder, Mervin C.;Mead, Laura E.;Ingram, David A.
有限的血管形成能力的内皮祖细胞（EPCs）输注到心血管功能障碍患者可能与误解的细胞的生物学潜力。EPC通常通过细胞表面抗原表达或在鉴定“内皮细胞集落形成单位”（CFU-EC）的市售试剂盒中计数来鉴定。然而，CFU-ECs的起源、增殖潜力和分化能力仍存在争议。相反，其他具有血管形成能力的EPCs，称为内皮集落形成细胞（ECFCs），已从人外周血中分离出来。我们比较了CFU-EC和ECFC的功能，并使用祖细胞测定和分析来自在造血干细胞克隆中携带Janus激酶2 V617 F突变的真性红细胞增多症患者的供体细胞，确定CFU-EC来源于造血系统。此外，CFU-EC具有骨髓祖细胞活性，分化成吞噬巨噬细胞，并且不能在体内形成灌注血管。相反，ECFC在克隆上不同于CFU-EC，显示出强大的增殖潜力，并在体内形成灌注血管。因此，这些研究确定CFUECs不是EPCs，并且在进一步的临床试验之前必须重新检查这些细胞在血管生成中的作用，而ECFCs可以作为血管再生的潜在疗法。
The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colonyforming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFUECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.