Engineering human islet organoids from iPSCs using an organ-on-chip platform

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Regenerative Medicine

Background:

• Human pluripotent stem cell (hPSC)-derived islet cells are valuable for diabetes research and cell therapy.
• Developing biomimetic human islet organoids from hPSCs is currently challenging.
• Organoid technology offers new in vitro models for disease and regenerative medicine.

Purpose of the Study:

• To engineer biomimetic human islet organoids using a novel organ-on-a-chip platform.
• To improve the differentiation and maturation of human induced pluripotent stem cell (hiPSC)-derived islet organoids.
• To establish a robust platform for organoid engineering, disease modeling, and drug testing.

Main Methods:

• Utilized an organ-on-a-chip microsystem with a multi-layer microfluidic device.
• Applied stem cell developmental principles for controllable embryoid body (EB) aggregation and pancreatic differentiation.
• Employed perfused 3D culture within the microfluidic device for islet organoid generation.

Main Results:

• Generated heterogeneous islet organoids containing α- and β-like cells with favorable growth and viability.
• Observed enhanced expression of pancreatic β-cell specific genes (PDX1, NKX6.1) and proteins (INS, C-peptide) under perfused conditions.
• Demonstrated more sensitive glucose-stimulated insulin secretion (GSIS) and higher Ca2+ flux compared to static cultures.

Conclusions:

• The organ-on-a-chip system effectively promotes endocrine cell differentiation and maturation of islet organoids.
• Perfusion culture in the microfluidic device is crucial for enhancing islet organoid function.
• This platform offers a robust and amenable system for real-time imaging and in situ tracking of islet organoid growth.