Mechanisms of In Vivo Cell Fusion

体内细胞融合机制

• 批准号: 7450731
• 负责人: ANDREW W DUNCAN
• 金额: $ 5.04万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7450731
• 关键词: Animal Model; Bone Marrow Cells; Cell fusion; Cells; Centrosome; Cytogenetics; Event; Frequencies; Fumarylacetoacetase; Genetic Markers; Genome Stability; Goals; Growth; Hematopoietic; Hematopoietic stem cells; Hepatic; Hepatocyte; Injury; Knockout Mice; Lead; Liver; Liver diseases; Metabolic; Methods; Mus; Numbers; Process; Proliferating; Property; Proteins; Therapeutic; Transplantation; Viral Envelope Proteins; chromosome loss; env Gene Products; in vivo; intrahepatic; liver function; nuclear reprogramming; segregation

DESCRIPTION (provided by applicant): Hepatocytes derived by cell fusion of transplanted bone marrow cells have the capacity to proliferate and completely restore abnormal liver function in an animal model of metabolic liver disease, the fumarylacetoacetate hydrolase (Fah) knockout mouse. However, spontaneous fusion is a very rare event and remains far below the threshold required for therapeutic utility unless the fusion products have a strong selective growth advantage. Furthermore, basic properties of fusion-derived hepatocytes such as genomic stability, centrosome number and efficiency of nuclear reprogramming are unknown. The overall goal of this application is to determine whether in vivo cell fusion could be a viable therapeutic strategy. To achieve this goal we will clarify some of the basic processes that lead to cell fusion in the liver. We will also delineate the properties of early and late fusion products. Finally, methods to enhance the efficiency of cell fusion in vivo will be studied. Aim 1: To elucidate details of the intrahepatic fusion process. Aim 2: To determine relevant properties of fusion-derived hepatocytes. Aim 3: To enhance in vivo cell fusion by expression of fusogenic viral envelope proteins.

描述（申请人提供）：在代谢性肝病动物模型——延胡索酰乙酰乙酸水解酶（Fah）基因敲除小鼠中，移植骨髓细胞的细胞融合衍生的肝细胞具有增殖能力并完全恢复异常肝功能。然而，自发融合是一种非常罕见的事件，并且仍然远远低于治疗用途所需的阈值，除非融合产物具有强大的选择性生长优势。此外，融合衍生肝细胞的基本特性，如基因组稳定性、中心体数量和核重编程效率尚不清楚。该应用的总体目标是确定体内细胞融合是否是一种可行的治疗策略。为了实现这一目标，我们将阐明导致肝脏细胞融合的一些基本过程。我们还将描述早期和晚期融合产物的特性。最后，将研究提高体内细胞融合效率的方法。目标 1：阐明肝内融合过程的细节。目标 2：确定融合衍生肝细胞的相关特性。目标 3：通过表达融合病毒包膜蛋白来增强体内细胞融合。