Shirota Toshihiko, Yasui Hisataka, Matsuda Takehisa
Department of Biomedical Engineering, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
Tissue Eng. 2003 Jun;9(3):473-85. doi: 10.1089/107632703322066651.
Rapid reendothelialization at an atherosclerotic lesion after balloon or stent inflation may be essential for maintaining homeostatic tissue function, which could reduce or prevent restenosis. We devised an endothelial progenitor cell (EPC)-enriched tubular hybrid tissue and mounted it on a small-diameter metallic stent (outer diameter, 1.5 mm), which is used for intravascular angioplasty to atherosclerotic lesions. This study addressed the fabrication technique and in vitro performance to verify lumenal endothelialization. A thin collagenous tubular tissue was prepared by contraction of collagen fibers by inoculated EPCs, which were isolated from canine peripheral blood and expanded ex vivo, in a collagen gel formed in a mold. An EPC-inoculated hybrid tissue-covered stent, loaded on a balloon catheter, was inserted into a tubular hybrid vascular medial tissue inoculated with smooth muscle cells (SMCs) as an arterial media mimic, and subjected to balloon inflation for enlargement (outer diameter, 3 mm), followed by balloon deflation. The EPC-inoculated hybrid tissue-covered stent tightly adhered to the lumenal surface of the hybrid medial tissue. On culture, EPCs in the hybrid tissue migrated and proliferated to form a completely endothelialized lumenal surface at stented sites as well as sites adjacent to the vascular hybrid medial tissue with the prolongation of culture. This in vitro pilot study before in vivo experiments suggests that an EPC-inoculated hybrid tissue-covered stent may be a novel therapeutic device for reendothelialization or paving with EPC-enriched tissue at an atherosclerotic arterial wall, resulting in the prevention of restenosis and the rapid formation of normal tissue.
球囊或支架扩张后，动脉粥样硬化病变处的快速再内皮化对于维持体内平衡组织功能可能至关重要，这可以减少或预防再狭窄。我们设计了一种富含内皮祖细胞（EPC）的管状混合组织，并将其安装在用于血管内血管成形术治疗动脉粥样硬化病变的小直径金属支架（外径1.5毫米）上。本研究探讨了制造技术和体外性能，以验证管腔内的内皮化情况。通过接种从犬外周血中分离并在体外扩增的EPC，使其在模具中形成的胶原凝胶中收缩胶原纤维，从而制备出薄的胶原管状组织。将装载在球囊导管上的接种了EPC的混合组织覆盖支架插入接种了平滑肌细胞（SMC）作为动脉中层模拟物的管状混合血管中层组织中，进行球囊扩张以扩大（外径3毫米），然后放气。接种了EPC的混合组织覆盖支架紧密粘附在混合中层组织的管腔表面。在培养过程中，随着培养时间的延长，混合组织中的EPC迁移并增殖，在支架部位以及与血管混合中层组织相邻的部位形成完全内皮化的管腔表面。这项在体内实验之前进行的体外初步研究表明，接种了EPC的混合组织覆盖支架可能是一种新型治疗装置，用于在动脉粥样硬化动脉壁处进行再内皮化或用富含EPC的组织铺路，从而预防再狭窄并快速形成正常组织。
