GMP-compliant iPS cell lines show widespread plasticity in a new set of differentiation workflows for cell replacement and cancer immunotherapy

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Daniel Terheyden-Keighley - , Catalent Düsseldorf GmbH (Author)
  • Melanie Hühne - , Catalent Düsseldorf GmbH (Author)
  • Thomas Berger - , Catalent Düsseldorf GmbH (Author)
  • Björn Hiller - , Catalent Düsseldorf GmbH (Author)
  • Soraia Martins - , Catalent Düsseldorf GmbH (Author)
  • Anna Gamerschlag - , Catalent Düsseldorf GmbH (Author)
  • Davood Sabour - , Catalent Düsseldorf GmbH (Author)
  • Andrea Meffert - , Catalent Düsseldorf GmbH (Author)
  • Andreas Kislat - , Catalent Düsseldorf GmbH (Author)
  • Carsten Slotta - , Catalent Düsseldorf GmbH (Author)
  • Francois Hafezi - , Catalent Düsseldorf GmbH (Author)
  • Jens Lichte - , Catalent Düsseldorf GmbH (Author)
  • Smita Sudheer - , Catalent Düsseldorf GmbH (Author)
  • Karen Tessmer - , Center for Regenerative Therapies Dresden, Chair of Cell Replacement in the Mammalian Retina (Author)
  • Katherina Psathaki - , University Osnabruck (Author)
  • Marius Ader - , Center for Regenerative Therapies Dresden, Chair of Cell Replacement in the Mammalian Retina (Author)
  • Gesine Kogler - , University Hospital Duesseldorf (Author)
  • Boris Greber - , Catalent Düsseldorf GmbH (Author)

Abstract

Cell therapeutic applications based on induced pluripotent stem cells (iPSCs) appear highly promising and challenging at the same time. Good manufacturing practice (GMP) regulations impose necessary yet demanding requirements for quality and consistency when manufacturing iPSCs and their differentiated progeny. Given the scarcity of accessible GMP iPSC lines, we have established a corresponding production workflow to generate the first set of compliant cell banks. Hence, these lines met a comprehensive set of release specifications and, for instance, displayed a low overall mutation load reflecting their neonatal origin, cord blood. Based on these iPSC lines, we have furthermore developed a set of GMP-compatible workflows enabling improved gene targeting at strongly enhanced efficiencies and directed differentiation into critical cell types: A new protocol for the generation of retinal pigment epithelium (RPE) features a high degree of simplicity and efficiency. Mesenchymal stromal cells (MSCs) derived from iPSCs displayed outstanding expansion capacity. A fully optimized cardiomyocyte differentiation protocol was characterized by a particularly high batch-to-batch consistency at purities above 95%. Finally, we introduce a universal immune cell induction platform that converts iPSCs into multipotent precursor cells. These hematopoietic precursors could selectively be stimulated to become macrophages, T cells, or natural killer (NK) cells. A switch in culture conditions upon NK-cell differentiation induced a several thousand-fold expansion, which opens up perspectives for upscaling this key cell type in a feeder cell-independent approach. Taken together, these cell lines and improved manipulation platforms will have broad utility in cell therapy as well as in basic research.

Details

Original languageEnglish
Pages (from-to)898-911
Number of pages14
JournalStem cells translational medicine
Volume13
Issue number9
Publication statusPublished - 23 Jul 2024
Peer-reviewedYes

External IDs

ORCID /0000-0001-9467-7677/work/218583328
PubMed 39042522

Keywords

ASJC Scopus subject areas