Partial hepatectomy and bile duct ligation in rainbow trout (Oncorhynchus mykiss): Histologic, immunohistochemical and enzyme histochemical characterization of hepatic regeneration and biliary hyperplasia

Hepatic regeneration following partial hepatectomy (PH) and biliary hyperpl asia subsequent to bile duct ligation (BDL) were characterized in rainbow t rout (Oncorhynchus mykiss) by light microscopy using routine and special (i mmunohistochemical and enzyme histochemical) stains. Both PH and BDL involv ed initial hypertrophy and hyperplasia of bile preductular epithelial cells (BPDECs). BPDECs are small oval cells that form junctional complexes with hepatocytes and bile ductular cells and are commonly found in hepatic tubul es of teleost liver. Proliferating BPDECs transitioned through intermediate cell types before final differentiation into large basophilic hepatocytes (following PH) or biliary epithelial cells (after BDL). Normal BPDECs and h epatocytes were both negative for cytokeratin intermediate filaments in con trol fish when screened with the monoclonal antibody AE1/AE3. In contrast, hyperplastic BPDECs and their progeny (intermediate cells, immature hepatoc ytes, ductal epithelial cells) were all strongly cytokeratin positive. Cyto keratin expression was transient in newly differentiated hepatocytes (expre ssion decreased as hepatocytes acquired characteristics consistent with ful l differentiation) but was permanent in biliary epithelial cells (expressio n was very strong in large mature ducts). BPDECs, intermediate cells, and i mmature ductal cells were also strongly positive for alkaline phosphatase f ollowing BDL. Chronology of histologic events and cytokeratin and enzyme ex pression all support the hypothesis that BPDECs possess the capacity to dif ferentiate into either hepatocytes or biliary epithelial cells. Thus, BPDEC s may be the teleost equivalent of a bipolar hepatic stem cell in mammals.