人骨髓间充质干细胞向肝样细胞分化的体内外实验研究

发布时间：2018-11-03 07:23

【摘要】：研究背景肝脏疾患是影响人类生活质量和生命健康的重要疾病之一。不管其病因如何，这些疾病都将逐渐发展，演变为肝纤维化或肝硬化，最终出现肝脏功能衰竭。对于各种类型的终末期肝病，肝移植在理论上应该为最理想的治疗选择。但由于供体缺乏及保存供体的时间限制的原因，很多病人在等待肝移植的过程中即死亡。生物人工肝系统能使终末期肝病病人桥接肝移植。肝细胞具有强大的再生能力，临时应用生物人工肝系统也可以解决急性肝功能的失代偿，促进肝细胞再生，肝功能可以暂时恢复，争取到等待肝移植的时间。经过几十年的研究，生物人工肝系统已从非生物型、生物型人工肝系统发展到混合型人工肝系统，国内外已经有不少种类的人工肝系统应用于临床。肝细胞是生物人工肝系统的主要生物成分，，生物人工肝系统的支持作用主要来源于肝细胞的生物代谢功能。然而肝细胞不易在体外培养生长，如何获得高质量、来源丰富的肝细胞是生物人工肝和干细胞移植面临的共同问题。目前肝细胞来源主要是人源性肝细胞和动物源性肝细胞，但都各有不同的缺陷。最为理想的是能在体外培养且保持肝细胞特性和功能的肝细胞，这种细胞必须具有合成代谢、解毒和生物转化功能并能长期存活，可以大量扩增，解决
[Abstract]:Background liver disease is one of the most important diseases affecting the quality of life and health of human beings. Regardless of the etiology, these diseases develop gradually, leading to liver fibrosis or cirrhosis, and ultimately liver failure. For various types of end-stage liver disease, liver transplantation should theoretically be the best treatment option. However, due to the lack of donors and the time limit of donor preservation, many patients died while waiting for liver transplantation. The bioartificial liver system can bridge liver transplantation in patients with end-stage liver disease. The temporary application of bioartificial liver system can also solve the decompensation of acute liver function and promote the regeneration of liver cells. The liver function can be temporarily recovered and the time of waiting for liver transplantation can be obtained. After decades of research, bioartificial liver system has been developed from abiotic and biological artificial liver system to mixed artificial liver system. Many kinds of artificial liver system have been applied in clinic at home and abroad. Hepatocytes are the main biological components of the bioartificial liver system, and the supporting function of the bioartificial liver system is mainly derived from the biological metabolic function of the hepatocytes. However, it is difficult for hepatocytes to grow in vitro. How to obtain high quality and abundant hepatocytes is a common problem in bioartificial liver and stem cell transplantation. At present, the main sources of hepatocytes are human hepatocytes and animal derived hepatocytes, but they all have different defects. Ideally, hepatocytes that can be cultured in vitro and maintain the characteristics and functions of hepatocytes must have the functions of synthesis, detoxification and biotransformation, and can survive for a long time, and can be expanded in large quantities.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R329.2

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