Hepatocytes of certain rat strains are spontaneously accepted when they are implanted in the peritoneal cavity. Therefore to evaluate if microcapsules are able to immunoisolate the hepatocytes, it is necessary to find the strain of rat whose free hepatocytes are rejected. Hepatocytes were collected from Buffalo rats and were implanted intraperitoneally in one year old Gunn rats. During the first two weeks both groups of Gunn rats which received free and encapsulated hepatocytes showed a reduction in the bilirubin level relative to the control. After 15 days, the bilirubin levels increased in the group which received free hepatocytes. This suggests that an acute rejection had taken place. Bilirubin continued to stay high until the end of the experiment and there was no difference between this group and the control. As the animal ages, there is a significant accumulation of bilirubin in the tissues which affects the net reduction of serum bilirubin since once bilirubin is conjugated by the transplanted hepatocytes and eliminated, some of the bilirubin deposited in the tissues diffuses into the blood preventing a major drop in serum bilirubin levels. The findings that UDP-glucuronosyltransferase (UDPGT) activity of Buffalo rat hepatocytes is the same as the UDPGT activity of Wistar rat hepatocytes, imply that the age of the animal is a very critical factor in determining how great the depression of serum bilirubin will be after implantation of hepatocytes.
Bilirubin-Induced Cerebellar Hypoplasia in Gunn Rats and Sequencing of Bilirubin UDP-Glucuronosyltransferase cDNA.
