HEPATOCYTES--TRANSPLANTATION, EXTRACORPOREAL SUPPORT

尽管已经描述了用于治疗的各种治疗方式， 肝功能不全，除了器官移植，没有人有 被证明在临床上有用。 肝移植并没有被广泛应用 由于成本高，技术难度大，需要精密的 技术和支持团队以及获得尸体捐赠者困难 机关 几位研究者试图开发一种技术， 肝细胞移植 这种方法的结果在很大程度上 令人失望的是，由于无法显示长期生存和保留 供体细胞的特异性肝型功能。 然而，成功 肝细胞移植将是有用的，因为它将允许存活 相关的供体使用，一个供体用于多个受体， 简单且成本有效，并且细胞可以被储存以备后用。 我们有 开发了一种技术，使肝细胞附着在胶原蛋白涂层的 导致肝细胞活力和功能延长的微球 无论是在体内还是体外。 我们假设可以使用这种技术 至（1.）腹腔内肝细胞移植新方法的建立 这将使移植细胞的存活率和功能得以延长 （2.）建立一个体外肝辅助系统， 支持直到宿主肝脏再生，以及（3.）开发一种新的方法 肝细胞的长期储存。 将进行一系列全面的体内和体外实验研究， 来检验我们的假设 新鲜制备或储存的 将微载体附着的肝细胞移植到古恩大鼠中， 对胆红素缺乏UDP葡萄糖醛酸基转移酶活性，无白蛋白血症大鼠， 和肝功能不全的大鼠（90%部分肝切除，脑病， 缺血性和化学性肝损伤），以纠正缺陷，改善肝脏 功能和提高生存。 类似地，微载体连接 将在体外灌注肝细胞，并检测特定肝细胞 功能;这种支持系统的能力，以提高动物的生存， 将测试肝功能不全的实验模型。 整体 我们研究的目的是确定 微载体粘附细胞在肝细胞移植和发育中的应用 体外肝脏支持系统

Although various therapeutic modalities have been described for treating liver insufficiency, with the exception of organ transplantation, none have proven to be clinically useful. Liver transplantation is not widely used because of the high cost, technical difficulty, need for sophisticated technology and support teams and difficulty in obtaining cadaver donor organs. Several investigators attempted to develop the technique of hepatocyte transplantation. Results with this method have been largely disappointing due to inability to show long-term survival and retention of specific hepatocype function of donor cells. However, successful hepatocyte transplantation would be useful because it would allow living related donor use, use of a single donor for multiple recipients, would be simple and cost-effective and cells could be stored for later use. We have developed a technique which allows hepatocyte attachment on collagen-coated microspheres which results in prolonged hepatocyte viability and function both in vivo and in vitro. We hypothesize that this technique can be used to (1.) Develop a new method of intra-peritoneal hepatocyte transplantation which will allow prolonged viability and function of transplanted cells (2.) To construct an extracorporeal liver assist system for metabolic support until the host liver regenerates and (3.) To develop a new method of storage of hepatocytes for long periods of time. A series of comprehensive in vivo and in vitro experimental studies will be carried out to test our hypotheses. Freshly prepared or stored microcarrier-attached hepatocytes will be transplanted into Gunn rats which lack UDPglucuronosyltransferase activity for bilirubin, analbuminemic rats, and rats with liver insufficiency (90% partial hepatectomy, encephalopathy, ischemic and chemical liver injury) to correct deficits, improve liver function and enhance survival. Similarly, microcarrier-attached hepatocytes will be perfused in vitro and tested for specific liver functions; the ability of this support system to improve animal survival in experimental models of liver insufficiency will be tested. The overall objective of our studies is to determine the efficacy of the microcarrier-attached cells in hepatocyte transplantation and in developing an extracorporeal liver support system.