人胎儿肝干细胞体外长期培养的实验研究
发布时间：2019-05-15 14:11
【摘要】：背景 我国重型肝炎或急性肝功能衰竭发生率较高,其病理特点是大块或亚大块肝细胞坏死,而残存肝细胞的增殖受到多种因素的抑制,因此依赖病变肝脏自身的能力引发肝再生困难。 原位肝移植(OLT)是迄今为止治疗终末期肝病的有效的方法,但因供肝不足、费用昂贵且需终身使用免疫抑制剂等诸多因素限制了其临床应用。 肝细胞移植作为辅助治疗方法是肝脏移植的重要补充,但肝细胞的来源、数量、移植后肝细胞在体内的增殖和功能等问题尚未完全解决,阻碍着它的发展,理论上用正常人肝细胞作为细胞移植来源最为理想,但同样存在供体短缺的问题,且增殖能力较差;异种肝细胞虽然来源广泛,但又存在免疫排斥、病毒感染特别是逆转录病毒感染等问题;肝肿瘤细胞株增殖能力强,但存在肿瘤种植风险,且肝细胞功能较差;永生化细胞系应用最多的是SV40 LT基因转染的永生化肝细胞,虽解决了增殖难题,但安全性受到置疑。 人胎肝细胞可分泌细胞生长因子刺激离体细胞生长增殖,组织分化增殖能力强,且免疫原性弱,为较好的细胞来源;临床资料证实胎儿肝细胞移植在治疗肝功能衰竭、先天性酶缺乏等疾病方面有一定的价值,但同样存在供体缺乏及移植细胞增殖困难等问题。而肝干细胞可以解决这些问题,是因为它具有强大的增殖能力和双向分化潜能,移植时仅需成熟肝细胞数量的1/3～1/5,并且胎肝干细胞体积小,更易于从门静脉注射,移植后易于融入肝板,还有易于大量分离培养和基因操作等优点。研究表明处于生长静止期的成人肝脏中干细胞数量有限,而胎肝中富含大量肝干细胞,如果选取人胎儿肝干细胞作为细胞移植来源,就可避免未知病原体感染和异种基因导入人体,因此,体外成功分离纯化人胎儿肝干细胞,并对其进行培养扩增无疑具有非常重要的意义。 本实验对人胎儿肝干细胞体外分离培养扩增做了初步探索,旨在寻找对其进
[Abstract]:Background the incidence of severe hepatitis or acute liver failure in China is high. The pathological characteristics of severe hepatitis or acute liver failure are large or submassive hepatocytes, while the proliferation of residual hepatocytes is inhibited by many factors. Therefore, it is difficult to regenerate the liver by relying on the ability of the diseased liver itself. Orthopaedic liver transplantation (OLT) is an effective method for the treatment of end-stage liver disease so far, but its clinical application is limited by many factors, such as insufficient donor liver, high cost and lifelong use of immunosuppressive agents. As an auxiliary therapy, liver cell transplantation is an important supplement to liver transplantation, but the source and quantity of hepatocytes, the proliferation and function of hepatocytes in vivo have not been completely solved, which hinders its development. In theory, normal human hepatocytes are the most ideal source of cell transplantation, but there is also a shortage of donors, and the proliferation ability is poor. Although heterogeneic hepatocytes come from a wide range of sources, there are some problems, such as immune rejection, viral infection, especially retrovirus infection, and the proliferation ability of liver tumor cell lines is strong, but there is a risk of tumor implantation, and the function of hepatocytes is poor. Immortalized cell lines are most widely used in immortalized hepatocytes transfected with SV40 LT gene. Although the proliferation problem has been solved, the safety of immortalized cell lines has been questioned. Human fetal hepatocytes can secrete cell growth factor to stimulate the growth and proliferation of isolated cells, the ability of tissue differentiation and proliferation is strong, and the immunogenicity is weak, so it is a good cell source. Clinical data confirmed that fetal liver cell transplantation has certain value in the treatment of liver failure, congenital enzyme deficiency and other diseases, but there are also some problems, such as lack of donor and difficulty in proliferation of transplantation cells. Liver stem cells can solve these problems because they have strong proliferation and bidirectional differentiation potential, only 1 鈮，
本文编号：2477564
[Abstract]:Background the incidence of severe hepatitis or acute liver failure in China is high. The pathological characteristics of severe hepatitis or acute liver failure are large or submassive hepatocytes, while the proliferation of residual hepatocytes is inhibited by many factors. Therefore, it is difficult to regenerate the liver by relying on the ability of the diseased liver itself. Orthopaedic liver transplantation (OLT) is an effective method for the treatment of end-stage liver disease so far, but its clinical application is limited by many factors, such as insufficient donor liver, high cost and lifelong use of immunosuppressive agents. As an auxiliary therapy, liver cell transplantation is an important supplement to liver transplantation, but the source and quantity of hepatocytes, the proliferation and function of hepatocytes in vivo have not been completely solved, which hinders its development. In theory, normal human hepatocytes are the most ideal source of cell transplantation, but there is also a shortage of donors, and the proliferation ability is poor. Although heterogeneic hepatocytes come from a wide range of sources, there are some problems, such as immune rejection, viral infection, especially retrovirus infection, and the proliferation ability of liver tumor cell lines is strong, but there is a risk of tumor implantation, and the function of hepatocytes is poor. Immortalized cell lines are most widely used in immortalized hepatocytes transfected with SV40 LT gene. Although the proliferation problem has been solved, the safety of immortalized cell lines has been questioned. Human fetal hepatocytes can secrete cell growth factor to stimulate the growth and proliferation of isolated cells, the ability of tissue differentiation and proliferation is strong, and the immunogenicity is weak, so it is a good cell source. Clinical data confirmed that fetal liver cell transplantation has certain value in the treatment of liver failure, congenital enzyme deficiency and other diseases, but there are also some problems, such as lack of donor and difficulty in proliferation of transplantation cells. Liver stem cells can solve these problems because they have strong proliferation and bidirectional differentiation potential, only 1 鈮，
本文编号：2477564
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