AIM: To observe the therapeutic effect of intrasplenic transplantation with embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic milk (TX) mouse modeling Wilson disease.

METHODS: Donor hepatocytes were harvested from 14-d fetal liver of a pregnant homogeneous DL mouse. These cells were successively cultured, labeled with fluorescein dye Hoechst 33342 for 24 h, and sequentially infused into the spleen parenchyma of the recipient TX mice. No host immunosuppression measures were taken. Two and four weeks after transplantation, the recipients were killed for routine histologic investigation and immunohistochemistry study up to 4 wk after transplantation. The serum copper and ceruloplasmin concentrations of the recipient mice were determined by graphite furnace atomic absorption spectroscopy.

RESULTS: In the following 2^nd and 4^th wk after transplantation, the donor hepatocytes could be visualized in the livers of 47.3% recipients. The serum ceruloplasmin and copper concentrations increased by 1.6-fold after 2 wk and 2.0-fold times after 4 wk respectively, which ultimately rose from about 30% of the normal level to nearly 60% (P<0.01). The hepatic copper concentration decreased 7.2%, 4 wk after transplantation. Pathologic examination showed that there were many actively proliferative hepatocyte precursor cells with specific embryonic hepatocyte marker AFP migrated into hepatic sinusoids of the recipients. A large number of cells carrying hepatocytes marker and albumin were observed in the recipient spleen tissues.

CONCLUSION: Embryonic hepatocytes are capable of differentiating into mature hepatocytes in vivo. After transplantation, the hereditary abnormalities of copper metabolism in TX mice could be corrected partially by intrasplenic transplantation of homogeneous embryonic hepatocytes.

• Transplantation
• Wilson disease
• Copper
• Ceruloplasmin

• Animals
• Copper/blood
• Copper/toxicity
• Disease Models, Animal
• Female
• Fetal Tissue Transplantation
• Hepatocytes/transplantation
• Hepatolenticular Degeneration/chemically induced
• Hepatolenticular Degeneration/pathology
• Hepatolenticular Degeneration/therapy
• Male
• Mice
• Milk
• Pregnancy
• Spleen

AIM: To study the effect of allogeneic hepatocytes transplantation (HcT) intraperitoneally, intrasplenically or through vena portae in rats with acute hepatic failure (AHF) induced by D-galactosamine (D-gal).

METHODS: AHF rats were induced by D-gal. HcT was carried out 60h after intoxication, and all rats were divided into six groups: GroupⅠ received 2×10¹⁰/L hepatocytes 1 mL intraperitoneally with cyclosporin A (CsA) at 10 mg/kg simultaneously; Group Ⅱ received 1 mL normal saline (NS) intraperitoneally with CsA10 mg/kg; Group Ⅲ received 2×10¹⁰/L hepatocytes 1 mL through vena portae; Group Ⅳreceived 1mL NS through vena portae; Group Ⅴreceived 2×10¹⁰/L hepatocytes 1 mL intrasplenically; Group Ⅵ received 1 mL NS intrasplenically. After 1 wk the survival rates, liver function and liver histology of all rats were observed.

RESULTS: The survival rate of Group Ⅰ was higher than that of GroupⅡ (60 % vs 20%, P < 0.01), and their liver function and liver histology were obviously improved as compared with GroupⅡ. Similarly, the survival rate of Group Ⅴ was higher than that of Group Ⅵ (47% vs 20%, P < 0.05), and the liver function and liver histology were also improved in GroupⅤas compared with Group Ⅵ. On the other hand, the survival rate of Group Ⅲ was similar to that of GroupⅥ (20% vs 13.3%, P > 0.05), and their liver function and liver histology were also not improved significantly as compared with Group Ⅱ.

CONCLUSION: After HcT intraperitoneally or intrasplenically, the survival rates of AHF rats intoxicated with D-gal are increased, and the liver function and histology are also improved. On the contrary, the survival rate, liver function and liver histology of AHF rats through vena portae HcT are not improved.

• N/A