In vitro maintenance of terminal-differentiated state in hepatocytes entrapped within calcium alginate.

In cultured hepatocytes entrapped within Ca-alginate, liver-specific functions such as induction of tyrosine aminotransferase and serine dehydratase were stimulated by increasing the cell density. In contrast, a growth-related function such as induction of glucose-6-phosphate dehydrogenase was strongly stimulated by decreasing the cell density. This reciprocal regulation was mimicked by the addition of plasma membranes purified from adult rat liver to entrapment cultures at low cell density. Also, gluconeogenesis from lactate was stimulated by the addition of epinephrine (alpha,beta-agonist) with propranolol (beta-blocker). These results suggest that entrapped hepatocytes maintain not only terminal-differentiated state but also alpha-adrenergic response as shown in vivo.