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Updated: Sep 14, 2025

Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters

Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters

Published on: June 23, 2023

Micropocket-Based Differentiation System to Streamline and Scale Stem Cell-Derived Pancreatic Islet Production.

Susan O'Brien¹, Chen Li¹, Rusvir Trana²

¹Department of Chemical Engineering, McGill University, Montreal, QC H3A 0G4, Canada.

ACS Biomaterials Science & Engineering

|July 23, 2025

Summary

A novel micropocket hydrogel platform enables controlled aggregate size during stem-cell-derived islet production for type 1 diabetes. This scalable system prevents fusion and oxygen limitations, improving therapeutic potential.

Keywords:

Microwell controlled aggregation pancreatic dfferentiation stem cell-derived islets

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Differentiation of Human Pluripotent Stem Cells Into Pancreatic Beta-Cell Precursors in a 2D Culture System

Differentiation of Human Pluripotent Stem Cells Into Pancreatic Beta-Cell Precursors in a 2D Culture System

Published on: December 16, 2021

Area of Science:

Biotechnology
Regenerative Medicine
Cell Therapy

Background:

Stem-cell-derived islets (SC-islets) are a promising alternative to cadaveric islets for type 1 diabetes treatment.
Controlling SC-islet aggregate size is crucial for reproducibility and therapeutic efficacy.
Current methods face challenges in scalability and maintaining consistent aggregate dimensions due to fusion and oxygen limitations.

Purpose of the Study:

To develop and validate a scalable culture system for producing uniform SC-islets.
To address the limitations of conventional methods in controlling aggregate size during differentiation.
To enhance the potential for therapeutic applications of SC-islets.

Main Methods:

Fabrication of a micropocket hydrogel platform with a lip-and-funnel geometry to capture and protect cellular aggregates.
Aggregation and differentiation of pancreatic progenitor cells into SC-islets over 23 days within the micropockets.
Assessment of aggregate size, shear stress protection, and aggregate retention during media exchange.

Main Results:

The micropocket platform maintained consistent SC-islet aggregate sizes (136 μm ± 31 μm SD), comparable to human islets.
Aggregates in suspension culture exhibited uncontrolled growth (114 μm ± 8 μm SD to 275 μm ± 62 μm SD) due to fusion.
The micropockets reduced shear stress by approximately 50× and prevented aggregate loss during media exchanges, demonstrating scalability.

Conclusions:

The micropocket hydrogel system offers a robust and scalable method for producing uniform SC-islets.
This approach overcomes key challenges in SC-islet production, including aggregate fusion and microenvironmental control.
The technology holds significant potential for the therapeutic manufacturing of stem-cell-derived islets for type 1 diabetes treatment.