Nugent H M, Rogers C, Edelman E R
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Mass, USA.
Circ Res. 1999 Mar 5;84(4):384-91. doi: 10.1161/01.res.84.4.384.
The perivascular implantation of tissue-engineered endothelial cells around injured arteries offers an opportunity to study fundamental vascular physiology as well as restore and improve tissue function. Cell source is an important issue because the ability to implant either xenogeneic or allogeneic cells would greatly enhance the clinical applications of tissue-engineered grafts. We investigated the biological and immunological responses to endothelial cell xenografts and allografts in pigs 4 weeks after angioplasty of the carotid arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam matrices and implanted in the perivascular space of 42 injured arteries. Both porcine and bovine endothelial cell grafts reduced the restenosis index compared with control by 54% and 46%, respectively. Perivascular heparin release devices, formulated to release heparin at twice the rate of release of heparan sulfate proteoglycan from endothelial cell implants, produced no significant reduction in the restenosis index. Endothelial cell implants also reduced occlusive thrombosis compared with control and heparin release devices. Host immune responses to endothelial implants were investigated by immunohistochemical examination of explanted devices and by immunocytochemistry of serum samples. The bovine cell grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes, and caused an increase in antibodies detected in serum samples. Reduced cellular infiltration and no humoral response were detected in animals that received allografts. Despite the difference in immune response, the biological effects of xenografts or allografts did not differ significantly.
在受损动脉周围进行组织工程化内皮细胞的血管周围植入，为研究基本血管生理学以及恢复和改善组织功能提供了一个机会。细胞来源是一个重要问题，因为植入异种或同种异体细胞的能力将极大地增强组织工程移植物的临床应用。我们研究了猪颈动脉血管成形术后4周对内皮细胞异种移植物和同种异体移植物的生物学和免疫反应。将猪或牛主动脉内皮细胞在明胶海绵基质中培养，并植入42条受损动脉的血管周围间隙。与对照组相比，猪和牛内皮细胞移植物的再狭窄指数分别降低了54%和46%。血管周围肝素释放装置，其设计为以从内皮细胞植入物中释放硫酸乙酰肝素蛋白聚糖速率的两倍释放肝素，并未使再狭窄指数显著降低。与对照组和肝素释放装置相比，内皮细胞植入物也减少了闭塞性血栓形成。通过对取出装置的免疫组织化学检查和血清样本的免疫细胞化学来研究宿主对内皮植入物的免疫反应。牛细胞移植物显示有白细胞浸润，主要由淋巴细胞组成，并导致血清样本中检测到的抗体增加。在接受同种异体移植物的动物中未检测到细胞浸润减少和体液反应。尽管免疫反应存在差异，但异种移植物或同种异体移植物的生物学效应没有显著差异。
