LIVER REPOPULATION FOR LIVER INJURY AND GENE THERAPY

肝损伤的肝脏再生和基因治疗

• 批准号: 2623453
• 负责人: SANJEEV GUPTA
• 金额: $ 32.95万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-20 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2623453
• 关键词: SCID mouse; cell differentiation; cell growth regulation; cell line; cell transplantation; disease /disorder model; gene mutation; gene therapy; genetic models; genetically modified animals; human fetus tissue; injury; laboratory mouse; laboratory rat; liver cells; liver circulation; liver disorder; liver failure; liver pharmacology; liver regeneration; liver transplantation; model design /development; peptidyl dipeptidase; vasodilators

Our hypothesis has been that liver repopulation with parenchymal cells will help develop novel therapies and provide systems for addressing fundamental questions in liver biology. We and others have made significant progress in advancing these goals by identifying permissive conditions for hepatocyte survival and function, methods to increase the mass of transplanted hepatocytes, insights into hepatic gene transfer, and analysis of hepatic progenitor cells. However, more work is necessary before clinical applications of hepatocyte transplantation could be systematically analyzed. We propose a series of studies directed at further defining the safety of liver repopulation by analyzing transplanted cell biodistributions during manipulations to increase liver repopulation, amelioration of deleterious changes in the host liver emanating from cell transplantation, and mechanisms for improving cell engraftment in the normal or the diseased liver. We will begin to isolate and characterize progenitor cells derived from the fetal human liver and to isolate stable cell lines capable of differentiating into hepatocytes. To demonstrate the fate of progenitor human liver cells, we will develop novel genetic animal models, which will allow unequivocal analysis of transplanted cell survival, differentiation and human hepatocytes could be infected with hepatitis viruses to help develop models of disease. These systems will allow us and others to develop effective therapies and to address basic questions concerning mechanisms in hepatitis viral persistence and replication. In parallel bonafide animal models of acute and chronic liver disease in humans. Completion of our proposed studies will greatly advance fundamental knowledge of the ontogeny and differentiation of the liver, therapeutic potential of hepatocyte transplantation, and development of novel biological systems.

我们的假设是肝实质细胞的再生 将有助于开发新的疗法，并提供解决 肝脏生物学的基本问题。 我们和其他人 在通过确定允许的 肝细胞存活和功能的条件，增加肝细胞存活和功能的方法， 移植肝细胞的质量，对肝脏基因转移的见解， 和肝祖细胞的分析。 然而，更多的工作是 肝细胞移植临床应用前的必要性 可以进行系统分析。 我们提出了一系列的研究 旨在通过以下方式进一步确定肝脏再生的安全性： 分析操作过程中移植细胞的生物分布， 增加肝脏再生，改善 来自细胞移植的宿主肝脏，以及 改善正常或患病肝脏中的细胞植入。 我们将 开始分离和表征来源于细胞的祖细胞。 人胎肝和分离稳定的细胞系， 分化成肝细胞。 为了证明祖先的命运 人类肝细胞，我们将开发新的遗传动物模型， 将允许明确的移植细胞存活分析， 人肝细胞可感染肝炎病毒 病毒来帮助开发疾病模型。 这些系统将使我们能够 和其他人开发有效的治疗方法， 关于肝炎病毒持续存在和复制的机制。 在急性和慢性肝病的平行真实动物模型中， 在人类身上。 我们建议的研究完成后， 肝脏个体发育和分化的基础知识， 肝细胞移植的治疗潜力， 新的生物系统