Bone marrow transplantation results in donor-derived hepatocytes in an animal model of inherited cholestatic liver disease.
Cell transplantation is a potential therapy for acquired or inherited liver diseases. Donor-derived hepatocytes (DDH) have been found in humans and mice after bone marrow transplantation (BMT) but with highly variable frequencies in different disease models. To test the effect of liver repopulation after BMT in inherited cholestatic liver diseases, spgp (sister of P-glycoprotein, or bile salt export pump, abcb11) knockout mice, a model for human progressive intrahepatic cholestasis type 2 with defects in excreting bile salts across the hepatocyte canalicular membrane, were transplanted with bone marrow cells from enhanced green fluorescent protein (EGFP) transgenic donor mice after lethal irradiation. One to 6 months later, scattered EGFP-positive DDHs with positive spgp staining were observed in the liver. These hepatocytes had been incorporated into hepatic plates and stained positively with hepatocyte-specific marker albumin. RT-PCR for the spgp gene revealed positive expression in the liver of sgsp knockout mice that had received the transplant. Bile acid analysis of bile samples showed that these mice also had higher levels of total biliary bile acid and taurocholic acid concentration than knockout mice without transplantation, indicating that BMT partially improved biliary bile acid secretion. Our results indicate that bone marrow cells could serve as a potential source for restoration of hepatic functions in chronic metabolic liver disease.
Department of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan, ROC.
Huey-Ling
HL
Chen
Renxue
R
Wang
Hui-Ling
HL
Chen
Wuh-Liang
WL
Hwu
Yung-Ming
YM
Jeng
Mei-Hwei
MH
Chang
Victor
V
Ling
D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D016026:Bone Marrow Transplantation; D002779:Cholestasis / Q000628:therapy*; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000166:cytology*; D008099:Liver / Q000166:cytology; D008107:Liver Diseases / Q000628:therapy*; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D018183:Transplantation Chimera
D001647:Bile Acids and Salts