IMPROVED BIOARTIFICAL LIVER FUNCTION IN HEPATIC FAILURE

描述：(改编自申请人的摘要)本申请 建议开发一种生物人工肝(BAL)作为桥梁 用于肝移植或患者自愈的装置 患有急性肝功能衰竭。目前开发的BAL存在以下问题 肝细胞失去了重要的合成和生物转化 功能。实验室的初步工作表明，细胞/细胞和 细胞/基质相互作用对肝细胞分化和 功能。赠款的假设是，通过理解和 细胞/基质和细胞/细胞中黏附受体的调控 肝细胞分化与生物转化的相互作用 改善了BAL的疗效，并因此提高了疗效。具体目标 1.为了证明大鼠之间的黏附受体相互作用 猪肝细胞和培养底物或其他肝细胞调节 生物转化功能；2.P450的药物诱导依赖于基质 将提高BAL的生物转化能力；3. 证明了一种由基质包裹的肝细胞组成的优化的BAL 用P450诱导剂的组合预处理的球体将提供 在犬肝功能衰竭模型中的卓越治疗效果。

DESCRIPTION: (Adapted from the applicant's abstract) This application proposes to develop a bioartificial liver (BAL) to be used as a bridging device to liver transplantation or for spontaneous recovery for patients with acute liver failure. The problems with the currently developed BAL are that the liver cells lose important synthetic and biotransformation functions. Preliminary work from the laboratory suggests that cell/cell and cell/matrix interactions are important for hepatocyte differentiation and function. The hypothesis of the grant is that by understanding and manipulating adhesion receptors involved in cell/matrix and cell/cell interactions that hepatocyte differentiation and biotransformation can be improved, and therefore improve the efficacy of a BAL. The Specific Aims are: 1. To demonstrate that adhesion receptor interactions between rat or porcine hepatocytes and the culture substratum or other liver cells regulate biotransformation functions; 2. Drug induction of P450 is matrix dependent and will enhance the biotransformation capacity of the BAL; 3. To demonstrate that an optimized BAL consisting of matrix entrapped hepatocyte spheroids pretreated with a combination of P450 inducers will provide superior therapeutic efficacy in a canine liver failure model.