HEPATOCYTES--TRANSPLANTATION, EXTRACORPOREAL SUPPORT

尽管已经描述了各种治疗方式来治疗 肝功能不全，除了器官移植外，没有人 已被证明在临床上有用。肝移植并未得到广泛应用 由于成本高、技术难度大、需要精密 技术和支持团队以及获得身体捐赠者的困难 器官。几位研究人员试图开发出一种 肝细胞移植。用这种方法得到的结果在很大程度上 令人失望，因为无法证明长期的生存和保留 供体细胞的特异性肝型功能。然而，成功地 肝细胞移植将是有用的，因为它将使 相关的捐赠者使用，将一个捐赠者用于多个接受者，将是 简单且经济实惠，细胞可以储存起来供以后使用。我们有 开发了一种允许肝细胞附着在胶原涂层上的技术 可延长肝细胞存活率和功能的微球 无论是在体内还是体外。我们假设这种技术可以用来 至(1.)发展一种新的腹膜内肝细胞移植方法 这将延长移植细胞的存活时间和功能 (2)体外肝脏代谢辅助系统的构建 支持直到宿主肝脏再生和(3)。开发一种新方法 肝细胞的长时间储存。 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。新鲜准备的或储存的 微载体附着的肝细胞将被移植到Gunn大鼠体内 胆红素、低蛋白血症大鼠缺乏UDP葡萄糖醛酸基转移酶活性 和肝功能不全的大鼠(90%肝部分切除，脑病， 缺血性和化学性肝损伤)，以纠正不足，改善肝脏 功能和提高存活率。类似地，微载体连接 肝细胞将在体外进行灌流，并进行特定肝脏的检测 功能；这一支持系统提高动物存活率的能力 将对肝功能不全的实验模型进行测试。整体而言 我们研究的目的是确定该药的疗效 微载体附着细胞在肝细胞移植和发育中的应用 一种体外肝脏支持系统。

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.