PROLIFERATION AND DIFFERENTIATION IN THE HUMAN FETAL ENDOCRINE PANCREAS

The morphogenesis and growth of the endocrine pancreas has not been we ll investigated in man although it represents an important issue in di abetology. We examined human fetal pancreas from 12 to 41 weeks of ges tation immunocytochemically to evaluate proliferative activity with th e Ki-67 marker, and cytodifferentiation with cytokeratin 19 (ductal ce lls), synaptophysin (all endocrine cells), and insulin, glucagon, soma tostatin and pancreatic polypeptide (islet cell types). Ki-67 labellin g was found in all these cell types but was much higher in ductal cell s than in islet cells. An intermediate population expressed synaptophy sin 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 inc luding the endocrine islet cells expressed cytokeratin 19. Thereafter cytokeratin 19 expression decreased and eventually disappeared from mo st 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 transitio nal differentiation stages between ductal and islet cells.