Long term organ culture of rat liver rudiment in a synthetic medium: Morphological and biochemical development

Abstract

Embryonic rat liver rudiments were grown and maintained in a chemically defined medium for up to 16 weeks. Liver explants grew and developed liver plates, bile canaliculi and ductules. Liver cells differentiated and, by the end of the second culture week, revealed cytological and ultrastructural features of adult rat liver cells. Glycogen synthetase activity appeared and reached a plateau within 2 weeks. Plasma proteins produced by the explants appeared sequentially in the culture medium. Their relative concentrations in the medium increased progressively to a plateau and they persisted throughout the culture period. Albumin was present in trace amounts during early days of culture. Its relative concentration increased and it became the major protein constituent of the medium by the second week. Transferrin, α 1M-globulin, haptoglobin, β 1c- and α 1B-globulin appeared in that order. The three fibrinogen subunits were identified during the first week of culture. Fetal proteins were identified during the early culture period, the most prominent being α-fetoprotein. The relative concentration of fetal proteins declined steadily as the culture progressed.