3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform

Area of Science:

• Biotechnology
• Regenerative Medicine
• Stem Cell Biology

Background:

• Organoids mimic in vivo organ systems for in vitro study.
• Human pluripotent stem cells (hPSCs) are a promising source for regenerative organoid engineering.
• Generating functional beta-like cells from hPSCs is key for islet organoid development.

Purpose of the Study:

• To engineer regenerative islet organoids with controlled size and cellular heterogeneity.
• To evaluate a novel hydrogel system, Amikagel, for islet organoid formation.
• To assess the maturation and function of engineered islet organoids.

Main Methods:

• Utilized Amikagel hydrogel for controlled aggregation of hPSC-derived pancreatic progenitor cells (hESC-PP).
• Engineered homogeneous and heterogeneous spheroids by controlling cell population integration.
• Induced hESC-PP spheroids towards mature beta-like cells and co-cultured with endothelial cells.

Main Results:

• Amikagel facilitated robust spheroid formation and enhanced expression of islet-specific genes (Pdx-1, NKX6.1).
• Engineered beta-like cells showed increased INS1 gene and C-peptide protein expression, with functional insulin secretion.
• Multicellular organoids with endothelial cells exhibited enhanced maturation and extracellular matrix development.

Conclusions:

• Amikagel is an effective platform for engineering precise and functional islet organoids.
• The developed platform supports the generation of mature, functional beta-like cells from hPSCs.
• This approach holds significant potential for advancing diabetes research and regenerative therapies.