Hoffmann Jan, Paul Angela, Harwardt Marc, Groll Jürgen, Reeswinkel Thomas, Klee Doris, Moeller Martin, Fischer Heike, Walker Tobias, Greiner Tim, Ziemer Gerhard, Wendel Hans P
Department of Thoracic, Cardiac and Vascular Surgery, University of Tuebingen, Tuebingen, Germany.
J Biomed Mater Res A. 2008 Mar 1;84(3):614-21. doi: 10.1002/jbm.a.31309.
Because of their insufficient biocompatibility and high thrombogenicity, small diameter artificial vascular prostheses still do not show a satisfactory patency rate. In vitro endothelialization of artificial grafts before implantation has been established experimentally years ago, but, this procedure is extremely time consuming and expensive. This study deals with the coating of graft surfaces with capture molecules (aptamers) for circulating endothelial progenitor cells (EPCs), mimicking a prohoming substrate to fish out EPCs from the bloodstream after implantation and to create an autologous functional endothelium. Using the SELEX technology, aptamers with a high affinity to EPCs were identified, isolated, and grafted onto polymeric discs using a blood compatible star-PEG coating. A porcine in vitro model that demonstrates the specific adhesion of EPCs and their differentiation into vital endothelial-like cells within 10 days in cell culture is presented. We suggest that the rapid adhesion of EPCs to aptamer-coated implants could be useful to promote endothelial wound healing and to prevent increased neointimal hyperplasia. We hypothesize that future in vivo self-endothelialization of blood contacting implants by homing factor mimetic capture molecules for EPCs may bring revolutionary new perspectives towards clinical applications of stem cell and tissue engineering strategies.
由于其生物相容性不足和高血栓形成性，小直径人工血管假体的通畅率仍不尽人意。多年前就已通过实验确立了在植入前对人工移植物进行体外内皮化的方法，但是，此过程极其耗时且昂贵。本研究涉及用捕获分子（适体）包被移植物表面，以捕获循环中的内皮祖细胞（EPC），模拟促归巢底物，在植入后从血流中捕获EPC，并形成自体功能性内皮。利用SELEX技术，鉴定、分离出对EPC具有高亲和力的适体，并使用血液相容性星形聚乙二醇涂层将其接枝到聚合物圆盘上。本文展示了一种猪体外模型，该模型证明了EPC在细胞培养中10天内的特异性黏附及其分化为有活力的内皮样细胞。我们认为，EPC与适体包被的植入物的快速黏附可能有助于促进内皮伤口愈合并防止内膜增生加剧。我们推测，未来通过用于EPC的归巢因子模拟捕获分子实现血液接触植入物的体内自内皮化，可能会为干细胞和组织工程策略的临床应用带来革命性的新前景。
