建立人鼠嵌合肝动物模型的实验研究

Establishment of an animal model of tolerant rats with chimeric human liver

Objective To determine whether genetically normal immunocompetent rodent hosts could be manipulated to accept human fetal hepatocyte transplants and survive without immunosuppression. Methods Tolerance to human hepatocytes was established by injection of human fetal hepatocytes into the peritoneal cavities of fetal Wistar rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24 h after birth to establish tolerant rats with chimeric human liver. Results Transplanted human fetal hepatocytes in rat livers were visualized at different time with different assays after birth. Human albumin protein was detected in rat serum by Western blotting from week 4 to 8. Human albumin mRNA was detected in rat livers by RT-PCR from week 4 to 10, and cell keratin from human hepatocyte of cytokeratin 18 was also detected in rat livers by immunohistochemical staining from week 4 to 12. Conclusion Human fetal hepatocytes could be introduced into an immunocompetent rats at the appropriate time during fetal development, which could be rendered tolerant and serve as suitable hosts to human hepatocyte transplants after birth without either genetic or pharmacological generalized immunosuppression, and the survival time of functional human hepatocytes was 12 weeks.