Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells

Area of Science:

• Cell biology
• Endocrinology
• Regenerative medicine

Background:

• Pancreatic beta cells are crucial for insulin production.
• Beta cell regeneration is limited in adults, posing challenges for diabetes treatment.

Purpose of the Study:

• To investigate the potential of adult human islet-derived cells for beta cell regeneration.
• To characterize the transition of islet cells to a mesenchymal state and their redifferentiation.

Main Methods:

• Isolation and culture of fibroblast-like cells from adult human islets.
• Induction of differentiation into hormone-expressing islet-like cell aggregates.
• Immunohistochemistry, in situ hybridization, and single-cell mRNA measurements to track cell transitions.

Main Results:

• Adult human islet-derived fibroblast-like cells proliferate readily in vitro.
• These mesenchymal-type cells can be induced to differentiate into insulin-expressing islet-like cell aggregates.
• Demonstrated a clear transition from epithelial to mesenchymal and back to epithelial cell states.

Conclusions:

• Adult human islet cells possess plasticity, enabling dedifferentiation and redifferentiation.
• This plasticity offers a promising avenue for generating functional beta cells for therapeutic purposes.
• The findings support the potential of using islet-derived mesenchymal cells for regenerative strategies in diabetes.