Intrasplenic Hepatocyte Transplantation on Allogenic Immunosuppressed Rat ; Survival of Transplanted Cells and Threapeutic Effect of Acute Hepatic Failure

Chung, Kyu Won; Sun, Hee Sik; Kim, Boo Sung; Park, Doo Ho; Lee, Chang Don; Suh, Jeong Min; Cho, Se Hyun; Han, Nam Ik; Kim, Sung Soo; Yoon, Seung Kew

Abstract

BACKGROUND/AIMS
Recent studies have shown that purified hepatocyte may be immunogenic. We evaluated the survival of transplanted hepatocyte in rat spleen and the therapeutic effect of dimethylnitrosamine(DMNS) induced acute hepatic failure with or without immunosuppression after injecting the isolated allogenic hepatocyte into rat spleen.
METHODS
Rat hepatocyte were prepared according to a modification method of two step ex vivo perfusion of collagenase digestion. Isolated allogenic hepatocytes(2X10 cells) were injected into the spleen of normal or hepatic-failed Sprague-Dawley rats with or without cyclosporin(CsA) treatment for 2 wks.
RESULTS
Transplanted hepatocytes in allogenic normal rat spleen without CsA immunosuppression were undetected in 2 to 4 days, but detected for at least 14 days in cases using CsA immunosuppression. However, groups with allogenic hepatocytes transplantation(2Xl0 cells/rat) at 24 hr after DMNS were enhanced by the survival rate significantly without CsA administration (p<0.05), and also tended to have enhanced survival rate with CsA(p=0.56) compared to that of the controls. Furthermore, hepatocytes transplantation with or without CsA adminstration ameliorated serum level of albumin but not transaminase, bilirubin at 3 and 7 ciays in the rat with DMNS-induced hepatic failure compared to that of controls.
CONCLUSIONS
This data demonstrate that isolated and transplanted allogenic hepatocytes into the splenic parenchyma may be immunogenic, and rejected rapidly without CsA administration, but also reduced the mortality of the acute hepatic failure with or without CsA administration. Therefore, understanding the possible mechanism by which transplanted hepatocytes into the spleen reduced mortality of experimental acute hepatic failure requires further study.