Combinations of Activin A or Nicotinamide with the Pancreatic Transcription Factor PDX1 Support Differentiation of Human Amnion Epithelial Cells Toward a Pancreatic Lineage.

Abstract

The differentiation of multipotent stem cells toward a pancreatic lineage provides us with an alternative cell-based therapeutic approach to type 1 diabetes and enables us to study pancreas development. The current study aims to study the effect of growth factors such as activin A or nicotinamide, alone and in combinations with the transcription factor, PDX1 (pancreatic and duodenal homeobox-1), on human amnion epithelial cells (hAECs) toward a pancreatic lineage. Ectopic expression of Pdx1 followed by treatment of hAECs with nicotinamide for 4 days resulted in strong induction of pancreatic endoderm and pancreatic progenitor genes, including NKX6.1 and NEUROD1. Pancreatic lineage cells expressing PDX1, SOX17, and RFX6 are derived from Pdx1-transduced hAECs treated with activin A or nicotinamide, but not cells treated with activin A or nicotinamide alone. Our study provides a novel culture protocol for generating pancreas-committed cells from hAECs and reveals an interplay between Pdx1 and activin A/nicotinamide signaling in early pancreatic fate determination.