Proliferation and differentiation in the human fetal endocrine pancreas

The morphogenesis and growth of the endocrine pancreas has not been well investigated in man although it represents an important issue in diabetology. We examined human fetal pancreas from 12 to 41 weeks of gestation immunocytochemically to evaluate proliferative activity with the Ki-67 marker, and cytodifferentiation with cytokeratin 19 (ductal cells), synaptophysin (all endocrine cells), and insulin, glucagon, somatostatin and pancreatic polypeptide (islet cell types). Ki-67 labelling was found in all these cell types but was much higher in ductal cells than in islet cells. An intermediate population expressed synaptophysin but lacked islet hormones. With increasing gestational age the Ki-67 labelling index decreased from 17 to 4% in ductal cells, from 9 to 1% in synaptophysin-positive cells, and from 3 to 0.1% in insulin- or glucagon-positive cells. From 12 to 16 weeks, all epithelial cells including the endocrine islet cells expressed cytokeratin 19. Thereafter cytokeratin 19 expression decreased and eventually disappeared from most islet cells, whereas strong expression remained in the ductal cells. We show that differentiated human islet cells have only very limited proliferative capacity, and we demonstrate the existence of transitional differentiation stages between ductal and islet cells.