Differentiation of intrahepatic peribiliary glands and pancreatic acinar cells from the remodeling ductal plate in human fetuses

Abstract

In a recent article published in Gastroenterology, Carpentier et al.1 suggested that embryonic ductal plate cells give rise to cholangiocytes, periportal hepatocytes, and adult liver progenitor cells. Herein, the authors demonstrated that the ductal plate also gives rise to pancreatic acinar cells and intrahepatic peribiliary glands.2 The authors previously reported that clusters of pancreatic acinar cells are present in normal adult livers.3 The ductal plate is a double-layered cylindrical structure located in the periportal regions of the fetal liver (Fig. 1A).4-8 The ductal plate undergoes remodeling (Fig. 1B,C), leading to the normal cholangiocytes and intrahepatic peribiliary glands.4-8 The remodeling involves apoptosis and cell proliferation of the ductal plate. Several molecules, such as glycoconjugates, Levis y, Bcl-2, C-myc, tenascin, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, trypsin, pancreatic digestive enzymes, E-cadherin, and catenin, are involved in the process of ductal plate remodeling.2-10 Pancreatic acinar cell clusters develop from the remodeling ductal plate.4, 8 The authors again reviewed 42 fetal livers of various gestational ages and 32 postnatal livers, and observed that intrahepatic peribiliary glands developed from the remodeling ductal plate at 35 to 40 gestational weeks for fetal livers as well as in the infant livers. The authors also found that pancreatic acinar cells developed from remodeling and remodeled ductal plate at 38 to 40 gestational weeks for fetal livers (Fig. 1D) as well as infant livers of 1 to 3 months (Fig. 1E). Immunohistochemically, the pancreatic acinar cells contained pancreatic amylase, trypsinogen, and lipase. The development of intrahepatic bile ducts. (A) The ductal plate at 12 gestational weeks. Cytokeratin immunostaining, ×100. (B) Remodeling or remodeled ductal plate at 18 gestational weeks. Cytokeratin immunostaining, ×100. (C) The remodeling ductal plate (arrow) at 17 gestational weeks. The cells of the ductal plate invade into the portal mesenchyma (arrow). Hematoxylin and eosin, ×200. (D) The development of pancreatic acinar cells (arrow) at 39 gestational weeks. Hematoxylin and eosin, ×50. (E) Pancreatic acinar cells (arrow) develop from the remodeled ductal plate in a 2-month-old infant liver. Hematoxylin and eosin, ×200. Tadashi Terada M.D., Ph.D.*, * Department of Pathology, Shizuoka City Shimizu Hospital, Shizuoka, Japan.