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<p>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<sup>+</sup>NKX6.1<sup>+</sup>ISL1<sup>+</sup>), 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月29日

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  • 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

摘要

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.