JIANG Li,LAN Lin,LI Jun-gang,WANG Yu-ming,LIU Guo-dong.HepaRG cells engraftment treats acute liver failure in severe combined immuno-deficient mice after mouse-specific anti-Fas antibody inducement[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(18):1724-1727.
JIANG Li,LAN Lin,LI Jun-gang,WANG Yu-ming,LIU Guo-dong.HepaRG cells engraftment treats acute liver failure in severe combined immuno-deficient mice after mouse-specific anti-Fas antibody inducement[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(18):1724-1727.DOI:
HepaRG cells engraftment treats acute liver failure in severe combined immuno-deficient mice after mouse-specific anti-Fas antibody inducement
HepaRG细胞的小鼠为实验组(10只),未经HepaRG细胞移植的小鼠为对照组(10只)。观察小鼠的存活率、肝脏功能、肝组织变化情况。实验组移植4周免疫组化检测肝组织人白蛋白、人CK18、人Hep Par 1的表达,免疫荧光检测人白蛋白的表达。 结果 实验组小鼠有9只存活超过4周,而对照组小鼠3 d内先后死亡9只,实验组血清ALT和AST趋于正常,显著低于对照组(P0.01),且存活时间显著高于对照组(P0.01)。实验组经HepaRG细胞移植能避免Jo2 mAb所致肝组织出血、坏死,移植后4周免疫组化可见人白蛋白、CK18、Hep Par 1阳性表达细胞,肝组织免疫荧光可见人白蛋白阳性细胞的表达。 结论 移植HepaRG细胞可治疗Jo2 mAb腹腔注射小鼠诱导的急性肝衰竭,HepaRG细胞不仅在小鼠肝内存活,且得以增殖。
Abstract
Objective To investigate the effect of engrafting human liver cancer cell line HepaRG on mouse-specific anti-Fas monoclonal antibody (Jo2 mAb) induced acute liver failure(ALF) in the severe combined immunodeficient (SCID) mice and investigate the heteroplastic strategy of human hepatocyte. Methods ALF was induced by injecting Jo2 mAb (0.3 mg/kg) intraperitoneally in SCID mice. Mice from experimental group (n=10)received 2×10
6
HepaRG cells engraftment in the spleen w
ithin 24 h after Jo2 mAb administration
and another 10 ALF mice served as control. The survival rate of mice
liver function and liver morphology of all mice were observed. At 4 weeks post-engraftment
HepaRG cells was characterized by S-P immunohistochemical staining for human albumin
human cytokeratin 18 and human Hep Par 1
meanwhile
immunofluorescence staining for human albumin. Results Nine transplanted mice were survival in 4 weeks after treatment and 9 non-transplanted mice were dead successively within 3 d. Compared to control group
survival time was prolonged significantly and serum liver enzyme levels was reduced significantly either of experimental group (P0.01). HepaRG cells engraftment protected mice from Jo2 mAb mediated liver hemorrhage and hepatocyte apoptosis in contrast to matched nonengrafted mice. In 4 weeks post-engraftment
human albumin
CK18 and specific human Hep Par 1 were found by immunohistochemistry staining
so was human albumin by immunofluorescence staining. Conclusion HepaRG cells transplantation prolongs the survival time and attenuates histological changes of Jo2 mAb-induced ALF mice. The transplanted HepaRG cells may well survive and regenerate for some period.