Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia
Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia
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DOI：
10.1096/fj.04-3282fje
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Hatzopoulos, AK
中科院分区：
文献类型：
--
作者：
Kupatt, C;Horstkotte, J;Hatzopoulos, AK
从胚胎第 7.5 天的小鼠中分离出的克隆胚胎内皮祖细胞 (eEPC) 专门定位于小鼠肿瘤转移的缺氧区域，但不影响正常器官，也不会形成癌。基于这些结果，我们评估了 eEPC 在同基因和异种生物体缺血后增强血管化和限制器官功能障碍的潜力。通过逆向输注进行局部应用后，在慢性缺血的兔后肢中评估了 eEPC 的血管生成潜力。 eEPC 治疗改善了肢体灌注，同时毛细血管密度和侧支血管数量增加。缺血性心脏损伤后，对小鼠进行全身 eEPC 输注，可增加缺血后心输出量，通过左心室发展压以及收缩和舒张功能的显着改善来衡量。在体外，eEPC 强烈诱导主动脉环血管生长。为了解决这种内在血管生成潜力的分子基础，我们研究了 eEPC 转录组。全基因组 Affymetrix GeneChip 分析表明，eEPC 表达大量已知可诱导血管生成、组织重塑和器官发生的分泌因子，这些因子可能有助于 eEPC 介导的有益作用。我们的研究结果表明，eEPC 在严重缺血条件下诱导血管生长和心脏保护，为研究新血管形成和组织恢复机制提供了现成的来源。
Clonal embryonic endothelial progenitor cells (eEPCs) isolated from embryonic day 7.5 mice home specifically to hypoxic areas in mouse tumor metastases but spare normal organs and do not form carcinomas. Based on these results, we assessed the potential of eEPCs to enhance vascularization and limit organ dysfunction after ischemia in syngenic and xenotypic organisms. The angiogenic potential of eEPCs was evaluated in chronic ischemic rabbit hindlimbs after regional application by retroinfusion. eEPC treatment improved limb perfusion, paralleled by an increase in capillary density and collateral blood vessel number. Systemic eEPC infusion into mice after ischemic cardiac insult increased postischemic heart output measured by a marked improvement in left ventricle developed pressure and both systolic and diastolic functions. In vitro, eEPCs strongly induced vascular outgrowths from aortic rings. To address the molecular basis of this intrinsic angiogenic potential, we investigated the eEPC transcriptome. Genome-wide Affymetrix GeneChip analysis revealed that the eEPCs express a wealth of secreted factors known to induce angiogenesis, tissue remodeling, and organogenesis that may contribute to the eEPC-mediated beneficial effects. Our findings show that eEPCs induce blood vessel growth and cardioprotection in severe ischemic conditions providing a readily available source to study the mechanisms of neovascularization and tissue recovery.