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Abstract

The aim of this work was to determine the pattern of expression of hepatic bilirubin UDP-glucuronosyltransferase throughout fetal development in rats, with the purpose of using fetal hepatocytes at the most appropiate stage of development for transplantation into Gunn rats lacking bilirubin UDP-glucuronosyltransferase activity and then assessing the therapeutic capacity of the implants. The results show that at day 13 of gestational life there is already bilirubin UDP-glucuronosyltransferase gene expression. Twenty-one-day fetal hepatocyte transplantation was also performed into the spleens of hyperbilirubinemic Gunn rats, when alpha-fetoprotein mRNA is still detectable. At 15, 30, and 90 days after transplantation, a mild decrease in total bilirubin serum levels was observed. An increase in bile conjugated bilirubin also was observed at 30 and 90 days. These data suggest the favorable evolution of transplanted cells and show its feasibility for therapy.

In UteroHepatocellular Transplantation in Rats

“…In this work, we chose fetal hepatocytes instead of adult ones because, in previous studies of our laboratory, we found that these hepatoblasts keep all their potentialities and characteristics of low immunogenicity and high proliferativity [6, 17]. Moreover, the transplantation of cells in utero to cure fetuses with birth defects has several advantages; namely, (i) the fast growth of fetuses provides an unique opportunity for the settlement and expansion of the implanted cells; (ii) the fetal immunological immaturity and the potential to induce specific tolerance to the donor; (iii) the protective and sterile fetal environment contributes to isolate environmental pathogens; and (iv) the fact that precocious treatments are beneficial and critical to assure effectiveness [11].…”

“…There are different animal models that express as a marker an enzymatic deficiency to differentiate the isolated and transplanted cells from the host's hepatocytes [6] like the Gunn rat model [17] and the most used model F344 rats [18]. …”

Ideal Experimental Rat Models for Liver Diseases

“…For its elimination from the serum, bilirubin conjugates with glucuronic acid, and UGT1A1 (bilirubin UDP-glucuronosyltransferase) is the sole isoform of bilirubin glucuronidating UGT1 in humans or rats. 10 Genetic variations in the gene encoding UGT1A1 lead to complete or partial inactivation of the glucuronidation of bilirubin in the serum, which causes unconjugated bilirubin. This may lead to the development of hyperbilirubinemic conditions such as the Crigler-Najjar (CN) Syndrome in humans.…”