Restricted accessResearch articleFirst published online 2011-09
Induction of Pancreatic β-Cell–Like Cells from CD44 + /CD105 + Human Amniotic Fluids via Epigenetic Regulation of the Pancreatic and Duodenal Homeobox Factor 1 Promoter
Pancreatic and duodenal homeobox factor 1 (PDX-1) maintains β-cell function and differentiation via direct regulation of multiple islet cell genes. However, the molecular mechanisms involved in this process remain unknown. Here, we show that PDX-1 plays an important role in the induction of CD44+/CD105+ human amniotic fluid cells (HuAFCs) into functional pancreatic β-cell–like cells in vitro. CD44+/CD105+ HuAFCs were transfected with either siRNA targeting PDX-1 (siRNA-PDX-1) or mock plasmid (siRNA-MOCK). Following induction, siRNA-MOCK–transfected cells differentiated into β-cell–like cells that expressed multiple islet cell markers and produced insulin and C-peptide in a glucose-regulated manner. However, siRNA-PDX-1–transfected cells did not fully differentiate into β-cell–like cells. Further, we observed epigenetic changes at the PDX-1 gene locus in induced CD44+/CD105+ HuAFCs. Therefore, CD44+/CD105+ HuAFCs could be a source of human pancreatic β-cell–like cells with potential uses in cell replacement therapy for diabetes.
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