The effect of cotransplantation of nonparenchymal liver cells on the survival of intraperitoneally transplanted hepatocytes

Jung, Yong Hee; Dong, Seok Ho; Kim, Byung Ho; Jung, Sung Hoon; Lee, Chang Kyun; Jang, Jae Young; Kim, Hyo Jong; Chang, Young Woon; Chang, Rin

Abstract

BACKGROUND: Transplantation of primary hepatocytes (PH) has been shown to provide metabolic support during acute liver failure. However, PH are known to be subject to necrosis in the peritoneal cavity. This is because cell-cell interaction plays an important role in their survival, but the peritoneal cavity can not provide such an environment. We tried to improve the survival of PH by simultaneously transplanting nonparenchymal liver cells (NPL).
METHODS
PH from normal Wistar rats, either alone (10(9) cells/kg, group 1, n=10) or mixed with NPL (5x10(8) cells/kg, group 2, n=10) were transplanted into the peritoneal cavity of hyperbilirubinemic Gunn rats which are congenitally devoid of bilirubin glucuronidation. Liver cells from Gunn rats were transplanted as a control.
RESULTS
Bilirubin glucuronides (BG) were detected in the bile of both group 1 and 2 rats collected at 6 hours after transplantation, and reached peak levels in 4 days. However, in the third and fourth week, BG could be detected only in group 2 animals. The serum bilirubin levels were decreased by 12.1~18.9% of basal levels in the second and third week for group 2 rats, but decreased by 15.1% only in the second week for the group 1 rats. Using in situ hybridization, albumin mRNA positive cells could be detected until the fourth week for the group 2 animals, but only until the second week for the group 1 rats.
CONCLUSIONS
PH start functioning in a short time after intraperitoneal transplantation and simultaneous transplantation of NPL with PH can prolong the survival and function of transplanted hepatocytes.