关键词: Gene manipulation Histone deacetylase inhibitors Long-term proliferation Microencapsulation Porcine hepatocytes

Mesh : Animals Histone Deacetylase Inhibitors / pharmacology Hepatocytes / drug effects Swine Cell Proliferation / drug effects Mice Cells, Cultured Cell Differentiation / drug effects Stem Cells / drug effects

来  源:   DOI:10.1016/j.biopha.2024.116973

Abstract:
Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.
摘要:
肝细胞移植是治疗终末期肝病的有效方法。然而,由于人类肝细胞的供应有限,猪肝细胞作为一种潜在的替代来源已经引起了人们的注意。尽管如此,传统的原代猪肝细胞在功能维持和体外增殖方面表现出一定的局限性。这项研究发现,通过使用组蛋白去乙酰化酶抑制剂(HDACi),原代猪肝细胞可以成功重编程为具有高增殖潜力的肝祖细胞。该方法使猪肝细胞能够在体外长时间增殖,并在慢病毒介导的基因修饰中表现出增加的易感性。这些肝祖细胞可以很容易地分化为成熟的肝细胞,将微囊化移植到急性肝衰竭小鼠体内,显著提高生存率。本研究为猪肝细胞在终末期肝病治疗中的应用提供了新的可能。
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