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 hepatocarcinogenesis can function as stem cells capable of differentiating into hepatocytes 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 they are abundant in embryonic liver and decline in number during development. Albumin (ALB) serves as a liver-specific marker, and the isoenzymes of pyruvate kinase, M(2)-PK and L-PK, are used to identify immature and mature hepatocytes, respectively. Small oval-shaped cells expressing ALB, M(2)-PK and L-PK are found near the vascular spaces and portal areas in 20-day gestation (E20), E21, newborn, 3-day and 1-week-old rat liver. Similar cells expressing ALB and M(2)-PK, but not L-PK are seen only periportally in adult liver. These are abundant in early embryonic liver and decrease in number during development until only a few, located periportally, persist in the adult. Oval cells, located periportally 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.