THE OVAL-SHAPED CELL AS A CANDIDATE FOR A LIVER STEM-CELL IN EMBRYONIC, NEONATAL AND PRECANCEROUS LIVER - IDENTIFICATION BASED ON MORPHOLOGY AND IMMUNOHISTOCHEMICAL STAINING FOR ALBUMIN AND PYRUVATE-KINASE ISOENZYME EXPRESSION

Oval cells observed in some experimental models of hepatocarcinogenesi s can function as stem cells capable of differentiating into hepatocyt es and bile ductular cells. Using markers which characterise embryonic hepatocytes, we showed that oval cells display different patterns of gene expression, suggesting some are more mature than others. In this study we looked for oval cells in developing liver, predicting that th ey are abundant in embryonic liver and decline in number during develo pment. Albumin (ALB) serves as a liver-specific marker, and the isoenz ymes of pyruvate kinase, M(2)-PK and L-PK, are used to identify immatu re and mature hepatocytes, respectively. Small oval-shaped cells expre ssing ALB, M(2)-PK and L-PK are found near the vascular spaces and por tal areas in 20-day gestation (E20), E21, newborn, 3-day and 1-week-ol d rat liver. Similar cells expressing ALB and M(2)-PK, but not L-PK ar e seen only periportally in adult liver. These are abundant in early e mbryonic liver and decrease in number during development until only a few, located periportally, persist in the adult. Oval cells, located p eriportally a few days after commencing a choline-deficient, ethionine -supplemented diet, co-express ALE and M(2)-PK. Their similarity with respect to markers, morphology and location suggests that oval-shaped cells may be the progenitors of oval cells.