Replacement of Liver Function in Rats by Transplantation of Microcarrier-Attached Hepatocytes

Abstract

Isolated hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, can be attached to collagen-coated dextran microcarriers and transplanted by intraperitoneal injection into rats. Survival and function of the transplanted hepatocytes have been demonstrated in mutant rats lacking bilirubin-uridine diphosphate glucuronosyltransferase activity (Gunn strain) and rats with inherited lack of plasma albumin (Nagase analbuminemia rat strain). This simple technique promises to be useful in the treatment of acute liver failure in humans.

Perturbations in Ataxia Telangiectasia Mutant Signaling Pathways After Drug-Induced Acute Liver Failure and Their Reversal During Rescue of Animals by Cell Therapy

“…By contrast, spacious extrahepatic sites (eg, the peritoneal cavity) may accommodate many transplanted cells. 9,15,16 With appropriate scaffolds, transplanted hepatocytes may engraft in the peritoneal cavity and express metabolic or synthetic functions. Because NOD/SCID mice with RifPhen-MCT-induced ALF tolerated cell transplantation in the liver and peritoneal cavity, we were able to study cell therapy mechanisms in ALF.…”

The Liver Vascular Bed for Hepatocytes Cell Therapy and Tissue Engineering

“…In this respect, adult hepatocytes must interact with the various biomaterials, a process which is poorly understood and one of the key challenges to overcome in this field. Various hepatic tissue engineering approaches have been explored including the attachment of hepatocytes to microcarriers and encapsulated hepatocytes spheroids allowing for immunological protection and cell interaction (Demetriou et al 1986). Co transplantation is easier in within microcapsules that also have the advantage of immunological protection.…”

Acute Liver Failure

“…[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] Some of these developments may also address the issue of difficulty in finding a donor liver and use of alternative/innovative forms of transplantation. Artificial hepatic support systems are cell-based extracorporeal system incorporating hepatocytes, which take up various excretory and synthetic hepatic functions until the liver regenerates.…”

“…Hepatocyte transplantation uses hepatocytes rather than the whole organ for transplantation. [69][70][71][72][73][74][75] The procedure would be ideal for transfer of genes to individuals with genetic diseases, such as familial hypercholesterolemia, Griggler-Najjar syndrome, etc. Extracorporeal liver (ECL) support system involves the diversion of patient's circulation through a liver outside the body.…”