Reprogramming of human pancreatic exocrine cells to β-like cells

Area of Science:

• Endocrinology and Metabolism
• Cell Biology
• Regenerative Medicine

Background:

• Rodent acinar cells demonstrate plasticity, differentiating into duct, hepatocyte, and islet beta-like cells.
• The potential for similar transdifferentiation in adult human pancreatic exocrine cells remains largely unexplored.

Purpose of the Study:

• To investigate whether adult human pancreatic exocrine cells can be reprogrammed into insulin-producing cells.
• To explore a novel cell therapy strategy for type 1 diabetes.

Main Methods:

• Human exocrine cells were transduced with lentiviruses encoding activated MAPK and STAT3.
• Cells were cultured as monolayers or 3D structures, with some initially grown in suspension.
• Lineage tracing and long-term engraftment in immunocompromised mice were employed.

Main Results:

• Activation of MAPK and STAT3 induced proendocrine factor neurogenin 3 expression in 50-80% of human exocrine cells.
• Insulin-positive cells increased significantly when exocrine cells were initially cultured in suspension before 3D culture.
• Human acinar cells were identified as the source of Ngn3- and insulin-expressing cells.
• Engraftment in mice enhanced reprogramming efficiency.

Conclusions:

• Adult human exocrine pancreas cells can be reprogrammed into functional, transplantable insulin-producing cells.
• This reprogramming approach offers a potential new source for cell therapy in type 1 diabetes, leveraging the abundance of exocrine cells.