A call to action for deciphering genetic variants in human pluripotent stem cells for cell therapy

Nissim Benvenisty; Jonathan S Draper; Paul J Gokhale; Lyn Healy; Zoe Hewitt; Deborah Hursh; Adam Hodgson; Tenneille E Ludwig; Nancy Mah; Sarah E McClelland; Milena Mennecozzi; Florian T Merkle; Joanne C Mountford; Martin Pera; Alessandro Prigione; Tristan A Rodriguez; Andrea Rossi; Foad J Rouhani; Kourosh Saeb-Parsy; Lucia Selfa Aspiroz; Nika Shakiba; Claudia Spits; Peter D Tonge; Ivana Barbaric

doi:10.1016/j.stem.2025.03.003

A call to action for deciphering genetic variants in human pluripotent stem cells for cell therapy

Cell Stem Cell. 2025 Apr 3;32(4):508-512. doi: 10.1016/j.stem.2025.03.003.

Authors

Nissim Benvenisty¹, Jonathan S Draper², Paul J Gokhale³, Lyn Healy⁴, Zoe Hewitt³, Deborah Hursh⁵, Adam Hodgson³, Tenneille E Ludwig⁶, Nancy Mah⁷, Sarah E McClelland⁸, Milena Mennecozzi⁹, Florian T Merkle¹⁰, Joanne C Mountford¹¹, Martin Pera¹², Alessandro Prigione¹³, Tristan A Rodriguez¹⁴, Andrea Rossi¹⁵, Foad J Rouhani¹⁶, Kourosh Saeb-Parsy¹⁷, Lucia Selfa Aspiroz⁹, Nika Shakiba¹⁸, Claudia Spits¹⁹, Peter D Tonge²⁰, Ivana Barbaric²¹

Affiliations

¹ The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
² Stem Cell Network, Ottawa, ON K1R 1A4, Canada.
³ School of Biosciences, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
⁴ Human Embryo and Stem Cell Unit, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
⁵ Hursh Cell Therapy Consulting, LLC, Ashton, MD, USA.
⁶ WiCell Research Institute, Madison, WI, USA; University of Wisconsin - Madison, Madison, WI, USA.
⁷ Fraunhofer Institute for Biomedical Engineering (IBMT), Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach, Germany.
⁸ Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6AU, UK.
⁹ European Commission, Joint Research Centre (JRC), Ispra, Italy.
¹⁰ Department of Pharmacology, the Institute of Metabolic Science, and the Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
¹¹ Scottish National Blood Transfusion Service, Jack Copland Centre, Edinburgh EH14 4BE, UK.
¹² The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
¹³ Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹⁴ National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, UK.
¹⁵ Genome Engineering and Model Development Laboratory, IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
¹⁶ The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
¹⁷ Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
¹⁸ School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Premium Research Institute for Human Metaverse Medicine (PRIMe), Osaka University, Osaka, Japan.
¹⁹ Vrije Universiteit Brussel (VUB), Brussels Health Campus/Faculty of Medicine and Pharmacy, Research Group Genetics, Reproduction and Development, Laarbeeklaan 103, 1090 Brussels, Belgium.
²⁰ bit.bio, The Dorothy Hodgkin Building, Babraham Research Campus, Cambridge CB22 3FH, UK.
²¹ School of Biosciences, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK; Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK; INSIGNEO Institute, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK. Electronic address: i.barbaric@sheffield.ac.uk.

PMID: 40185071
DOI: 10.1016/j.stem.2025.03.003

Abstract

Human pluripotent stem cell (hPSC)-based therapies offer promise but pose potential risks due to culture-acquired genetic variants, some of which have been linked with cancer. An international workshop addressed these concerns, highlighting the need for improved strategies to stratify variants and chart a path toward definitive guidelines in hPSC-based therapy.

MeSH terms

Cell- and Tissue-Based Therapy* / methods
Genetic Variation*
Humans
Pluripotent Stem Cells* / cytology
Pluripotent Stem Cells* / metabolism