In vitro-cultured human islet cell monolayers: stemness markers and insulin recovery upon streptozotocin exposure.

We have investigated long-term in vitro-cultured human islet-derived cell monolayers (CM) to determine their suitability as source of newly generated beta-cells. Initial loss of the islet three-dimensional architecture resulted in rearrangement of pancreatic hormone and key transcriptional factor expression, or decreased insulin secretion, or declined glucose-stimulated insulin release, reflecting reversal to an immature precursor stage. However, upon exposure to several streptozotocin (STZ) concentrations, CM showed glucose-stimulated insulin release recovery and an increased synthesis of insulin mRNA. Possibly, this outcome could derive from eventual "stemness" properties of such cell populations, unfolded by subtoxic STZ-induced CM damage. To test this hypothesis, we have examined messenger and protein expression of embryonic stem cell markers (Nanog, Sox-2, Oct-4A), which varied in CM versus control whole human islets. Moreover, different STZ concentrations were shown to modulate marker expression in CM. All together our data preliminarily seem to indicate that CM may generate reconstituted insulin-producing cells likely due to their intrinsic, preexisting stemness properties.