Ferratge S, Boyer J, Arouch N, Chevalier F, Uzan G
Inserm U1197, Hôpital Paul Brousse, Bâtiment Lavoisier, 12-14 avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France.
Biomed Mater Eng. 2017;28(s1):S65-S74. doi: 10.3233/BME-171625.
Endothelial Colony Forming Cells (ECFCs) are obtained in culture from Circulating Endothelial Progenitor Cells. They display all characteristics of endothelial cells and they display stem cells features. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials, and exhibit vascular repair capabilities useful for the treatment of ischemic diseases. However, the link between immaturity and functional properties of CB-ECFCs is still poorly defined. We showed that these cells have a high clonogenic potential and are capable to be efficiently reprogrammed into induced pluripotent stem cells. Moreover, we analyzed the expression of a broad panel of genes involved in embryonic stem cell properties. We define a novel stem cell transcriptional signature for CB-ECFCs fora better characterization and stratification according to their stem cell profile. We then improved the yield of CB-ECFC production for obtaining cells more functional in fewer passages. We used Glycosaminoglycans (GAG), components from the extracellular matrix which potentiate heparin binding growth factor activities. GAG mimetics were designed, having the capacity to increase the yield of ECFC during the isolation process, to increase the number of colonies, improve adhesion, proliferation, migration and self-renewal. GAG mimetics have thus great interest for vascular regeneration in combination with ECFC. Our results show that CB-ECFC are immature cells harboring specific functions such as formation of colonies, proliferation and formation of vascular structures in vitro and in vivo.
内皮祖细胞集落形成细胞(ECFCs)是从循环内皮祖细胞经培养获得的。它们表现出内皮细胞的所有特征,同时也具有干细胞特性。脐血来源的ECFCs(CB-ECFCs)具有高克隆形成和增殖潜能,并展现出对缺血性疾病治疗有用的血管修复能力。然而,CB-ECFCs的不成熟性与功能特性之间的联系仍未明确界定。我们发现这些细胞具有高克隆形成潜能,并且能够高效重编程为诱导多能干细胞。此外,我们分析了一系列与胚胎干细胞特性相关基因的表达。我们为CB-ECFCs定义了一种新的干细胞转录特征,以便根据其干细胞特征进行更好的表征和分层。然后,我们提高了CB-ECFCs的产量,以便在更少的传代次数中获得功能更强的细胞。我们使用了糖胺聚糖(GAG),它是细胞外基质的成分,可增强肝素结合生长因子的活性。设计了GAG模拟物,其能够在分离过程中提高ECFCs的产量、增加集落数量、改善黏附、增殖、迁移和自我更新能力。因此,GAG模拟物与ECFCs联合用于血管再生具有极大的意义。我们的结果表明,CB-ECFCs是具有特定功能的未成熟细胞,如在体外和体内形成集落、增殖以及形成血管结构。