In Vitro Endothelialization of Biodegradable Vascular Grafts Via Endothelial Progenitor Cell Seeding and Maturation in a Tubular Perfusion System Bioreactor
In Vitro Endothelialization of Biodegradable Vascular Grafts Via Endothelial Progenitor Cell Seeding and Maturation in a Tubular Perfusion System Bioreactor
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DOI：
10.1089/ten.tec.2015.0562
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发表时间：
2016-07-01
影响因子：
3
通讯作者：
Fisher, John P.
中科院分区：
文献类型：
--
作者：
Melchiorri, Anthony J.;Bracaglia, Laura G.;Fisher, John P.
生物可降解血管移植物成功的一个关键挑战是建立一个健康的内皮。为了建立内皮细胞(ECs)的单层，已经开发了各种技术，包括细胞种植。血管移植物可以植入相关的细胞类型，并在植入前成熟。由于成人内皮细胞的低增殖能力和供体部位发病率的问题，使用内皮祖细胞(EPC)进行血管修复越来越受到人们的关注。在这项工作中，我们将早期内皮祖细胞的商业细胞系的增殖和分化能力与已建立的生物反应器系统相结合，以支持细胞种子血管移植物的饱和。血管移植物和生物反应器装置的所有组件都可以在市场上买到，并允许支架和培养系统的完全定制。这种生物反应器的设置能够控制通过移植物的流动，向内皮祖细胞施加流体剪应力，并影响细胞的增殖和分化。与在静态系统中种植和培养的移植物相比，在生物反应器系统中与内皮祖细胞培养的移植物相比，细胞数量和新生组织的形成显著增加。在生物反应器培养的EPC种子移植物中，也观察到成熟内皮组织标志物的表达增加。这些发现表明，可定制的生物反应器设置对于内皮祖细胞的增殖和成熟具有明显的优势。这样的策略可能有利于在血管组织工程应用中使用内皮祖细胞。
A critical challenge to the success of biodegradable vascular grafts is the establishment of a healthy endothelium. To establish this monolayer of endothelial cells (ECs), a variety of techniques have been developed, including cell seeding. Vascular grafts may be seeded with relevant cell types and allowed to mature before implantation. Due to the low proliferative ability of adult ECs and issues with donor site morbidity, there has been increasing interest in using endothelial progenitor cells (EPCs) for vascular healing procedures. In this work, we combined the proliferative and differentiation capabilities of a commercial cell line of early EPCs with an established bioreactor system to support thematuration of cell-seeded vascular grafts. All components of the vascular graft and bioreactor setup are commercially available and allow for complete customization of the scaffold and culturing system. This bioreactor setup enables the control of flow through the graft, imparting fluid shear stress on EPCs and affecting cellular proliferation and differentiation. Grafts cultured with EPCs in the bioreactor system demonstrated greatly increased cell populations and neotissue formation compared with grafts seeded and cultured in a static system. Increased expression of markers for mature endothelial tissues were also observed in bioreactor-cultured EPC-seeded grafts. These findings suggest the distinct advantages of a customizable bioreactor setup for the proliferation and maturation of EPCs. Such a strategy may be beneficial for utilizing EPCs in vascular tissue engineering applications.