Bompais Heidi, Chagraoui Jalila, Canron Xavier, Crisan Mihaela, Liu Xu Hui, Anjo Aurora, Tolla-Le Port Carine, Leboeuf Marylene, Charbord Pierre, Bikfalvi Andreas, Uzan Georges
INSERM U506, Hôpital Paul Brousse, Villejuif, France.
Blood. 2004 Apr 1;103(7):2577-84. doi: 10.1182/blood-2003-08-2770. Epub 2003 Nov 20.
Endothelial progenitor cells (EPCs) were shown to be present in systemic circulation and cord blood. We investigated whether EPCs display specific properties compared with mature endothelial cells. Human cord blood CD34+ cells were isolated and adherent cells were amplified under endothelial conditions. Expression of specific markers identified them as endothelial cells, also called endothelial progenitor-derived cells (EPDCs). When compared to mature endothelial cells, human umbilical vein endothelial cells (HUVECs) and human bone marrow endothelial cells (HBMECs), endothelial markers, were expressed to the same extent except for KDR, which is expressed more in EPDCs. They display a higher proliferation potential. Functional studies demonstrated that EPDCs were more sensitive to angiogenic factors, which afford these cells greater protection against cell death compared with HUVECs. Moreover, EPDCs exhibit more hematopoietic supportive activity than HUVECs. Finally, studies in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice demonstrated that human circulating EPCs are able to colonize a Matrigel plug. EPDCs display the morphology and phenotype of endothelial cells. Their functional features indicate, however, that although these cells have undergone some differentiation steps, they still have the properties of immature cells, suggesting greater tissue repair capabilities. Future use of in vitro amplified peripheral blood EPDCs may constitute a challenging strategy for cell therapy.
内皮祖细胞(EPCs)已被证明存在于体循环和脐带血中。我们研究了与成熟内皮细胞相比,EPCs是否具有特定特性。分离出人脐带血CD34+细胞,并在内皮条件下扩增贴壁细胞。特定标志物的表达将它们鉴定为内皮细胞,也称为内皮祖细胞衍生细胞(EPDCs)。与成熟内皮细胞、人脐静脉内皮细胞(HUVECs)和人骨髓内皮细胞(HBMECs)相比,除了KDR在EPDCs中表达更多外,内皮标志物的表达程度相同。它们具有更高的增殖潜能。功能研究表明,EPDCs对血管生成因子更敏感,与HUVECs相比,这些因子能为这些细胞提供更大的抗细胞死亡保护。此外,EPDCs比HUVECs表现出更强的造血支持活性。最后,在非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠中的研究表明,人循环EPCs能够在基质胶栓中定植。EPDCs表现出内皮细胞的形态和表型。然而,它们的功能特征表明,尽管这些细胞已经经历了一些分化步骤,但它们仍然具有未成熟细胞的特性,这表明它们具有更强的组织修复能力。体外扩增的外周血EPDCs的未来应用可能构成一种具有挑战性的细胞治疗策略。