Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts - Implications for cell-based vascular therapy
Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts - Implications for cell-based vascular therapy
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DOI：
10.1161/01.cir.0000096490.16596.a6
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发表时间：
2003-11-25
期刊：
影响因子：
37.8
通讯作者：
Dzau, VJ
中科院分区：
文献类型：
--
作者：
Griese, DP;Ehsan, A;Dzau, VJ
背景-以前曾报道过成人骨髓来源的血源性内皮细胞。这些细胞具有内皮祖细胞（EPC）的性质，并且可以被细胞因子动员并募集到新血管形成的部位，在那里它们分化成成熟的内皮细胞。目前的协议，从外周血中分离的内皮祖细胞依赖于富集和选择的CD 34 + mononuclearcells.Methods和Results -在这份报告中，我们描述了一个简化的方法，从外周血中分离和扩增的内皮祖细胞，并评估其治疗潜力为自体细胞为基础的治疗损伤的血管和假体移植。未分级单核细胞的一个子集表现出在选择性生长条件下体外分化为内皮细胞的潜力。通过表达LacZ报告基因的逆转录病毒载体离体有效地转导细胞，并且可以扩增以产生用于治疗应用的足够数量。这些细胞移植到球囊损伤的颈动脉和兔的生物假体移植物中，导致裸露的血管和移植物段的快速内皮化，从而显着减少neointimadeposition.Conclusions -我们的结论是，移植的内皮祖细胞可能发挥至关重要的作用，在重建内皮完整性受损的血管，从而抑制新生内膜增生。这些发现可能对血管疾病的新的和实用的基于细胞的疗法有影响。
Background - Blood-borne endothelial cells originating from adult bone marrow were reported previously. These cells have the properties of an endothelial progenitor cell (EPC) and can be mobilized by cytokines and recruited to sites of neovascularization, where they differentiate into mature endothelial cells. Current protocols for isolation of EPCs from peripheral blood rely on enrichment and selection of CD34+ mononuclear cells.Methods and Results - In this report, we describe a streamlined method for the isolation and expansion of EPCs from peripheral blood and evaluate their therapeutic potential for autologous cell-based therapy of injured blood vessels and prosthetic grafts. A subset of unfractionated mononuclear cells exhibited the potential to differentiate in vitro into endothelial cells under selective growth conditions. The cells were efficiently transduced ex vivo by a retroviral vector expressing the LacZ reporter gene and could be expanded to yield sufficient numbers for therapeutic applications. Transplantation of these cells into balloon-injured carotid arteries and into bioprosthetic grafts in rabbits led to rapid endothelialization of the denuded vessels and graft segments, resulting in significant reduction in neointima deposition.Conclusions - We conclude that transplantation of EPCs may play a crucial role in reestablishing endothelial integrity in injured vessels, thereby inhibiting neointimal hyperplasia. These findings may have implications for novel and practical cell-based therapies for vascular disease.