Shirota Toshihiko, Yasui Hisataka, Shimokawa Hiroaki, Matsuda Takehisa
Department of Biomedical Engineering, Graduate School of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Biomaterials. 2003 Jun;24(13):2295-302. doi: 10.1016/s0142-9612(03)00042-5.
Rapid re-endothelialization at an atherosclerotic lesion after balloon inflation or stent deployment may be essential for reducing or preventing local thrombus formation and restenosis. In order to prevent these complications via enhanced rapid re-endothelialization, we fabricated two types of endothelial progenitor cell (EPC)-seeded intravascular stent devices. One was a photocured gelatin-coated metallic stent, and the other was a microporous thin segmented polyurethane (SPU) film-covered stent on which photocured gelatin was coated. Both devices were seeded with ex vivo expanded EPCs obtained from canine peripheral blood. Seeded EPCs formed confluent monolayers onto surfaces of both photocured gelatin-coated stent struts and SPU film, and a majority of cells remained on surfaces of stents after stent expansion. The EPC-seeded stent was expanded in a tubular hybrid vascular medial tissue composed of vascular smooth muscle cells and collagen as an arterial media mimic. After 7-day culture, EPCs, which migrated from the stent struts, proliferated and endothelialized the luminal surfaces of the hybrid vascular medial tissue. This in vitro pilot study prior to in vivo experiments suggests that on-stent cell delivery of EPCs may be novel therapeutic devices for re-endothelialization or endothelium lining or paving at an atherosclerotic arterial wall, resulting in the prevention of on-stent thrombus formation and in-stent restenosis, as well as the rapid formation of normal tissue architecture.
球囊扩张或支架植入后，动脉粥样硬化病变处的快速再内皮化对于减少或预防局部血栓形成和再狭窄可能至关重要。为了通过增强快速再内皮化来预防这些并发症，我们制备了两种接种有内皮祖细胞（EPC）的血管内支架装置。一种是光固化明胶涂层金属支架，另一种是微孔薄分段聚氨酯（SPU）膜覆盖且涂覆有光固化明胶的支架。两种装置都接种了从犬外周血中体外扩增获得的EPC。接种的EPC在光固化明胶涂层支架支柱和SPU膜的表面形成汇合的单层，并且在支架扩张后大多数细胞仍留在支架表面。接种EPC的支架在由血管平滑肌细胞和胶原蛋白组成的管状混合血管中层组织中扩张，作为动脉中层模拟物。培养7天后，从支架支柱迁移的EPC增殖并使混合血管中层组织的管腔表面内皮化。在体内实验之前进行的这项体外初步研究表明，EPC在支架上的细胞递送可能是用于动脉粥样硬化动脉壁再内皮化或内皮衬里或铺设的新型治疗装置，从而预防支架上血栓形成和支架内再狭窄，以及快速形成正常组织结构。
