Scale up manufacturing approach for production of human induced pluripotent stem cell-derived islets using Vertical Wheel® bioreactors

Scale up manufacturing approach for production of human induced pluripotent stem cell-derived islets using Vertical Wheel® bioreactors

Abstract Advanced protocols show potential for human stem cells (SC)-derived islets generation under planar (2D) alone or three-dimensional (3D) cultures, but show challenges in scalability, cell loss, and batch-to-batch consistency. This study explores Vertical Wheel (VW)® bioreactor suspension tec...

Full description

Saved in:
Bibliographic Details
Main Authors: Nidheesh Dadheech, Mario Bermúdez de León, Zofia Czarnecka, Nerea Cuesta-Gomez, Ila Tewari Jasra, Rena Pawlick, Braulio Marfil-Garza, Sandhya Sapkota, Kevin Verhoeff, Haide Razavy, Perveen Anwar, Abhineet Singh, Nilanjan Ray, Doug O’ Gorman, Glen Jickling, James Lyon, Patrick MacDonald, A. M. James Shapiro
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-025-00409-y
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Advanced protocols show potential for human stem cells (SC)-derived islets generation under planar (2D) alone or three-dimensional (3D) cultures, but show challenges in scalability, cell loss, and batch-to-batch consistency. This study explores Vertical Wheel (VW)® bioreactor suspension technology to differentiate islets from human induced pluripotent stem cells, achieving uniform, transcriptionally mature, and functional SC-islets. A 5x increase in scale from 0.1 L to 0.5 L reactors resulted in a 12-fold (15,005–183,002) increase in islet equivalent count (IEQ) without compromising islet structure. SC-islets show enriched β-cell composition (~63% CPPT+NKX6.1+ISL1+), glucose responsive insulin release (3.9–6.1-fold increase), and reversed diabetes in STZ-treated mice. Single cell RNA sequencing and flowcytometry analysis confirmed transcriptional maturity and functional identity, similar to adult islets. Lastly, harvested SC-islet grafts demonstrate improved islet functionality and mature transcriptomic signatures. Overall, scale-up in VW® bioreactor technology enhances IEQ yield with minimal variability and reduced cell loss, offering a pathway for clinical-grade SC-islet production.
ISSN:2057-3995

Similar Items