Igarashi, Kyomi J, Kucinski, Iwo, Chan, Yan Yi et al. (14 more authors) (2023) Physioxia improves the selectivity of hematopoietic stem cell expansion cultures. Blood Advances. ISSN 2473-9537
Abstract
Hematopoietic stem cells (HSCs) are a rare hematopoietic cell type that can entirely reconstitute the blood and immune systems following transplantation. Allogeneic HSC transplantation (HSCT) is used clinically as a curative therapy for a range of hematolymphoid diseases, but remains a high-risk therapy due to potential side effects including poor graft function and graft-vs-host disease (GvHD). Ex vivo HSC expansion has been suggested as an approach to improve hematopoietic reconstitution from low-cell dose grafts. Here, we demonstrate that we can improve the selectivity of polyvinyl alcohol (PVA)-based mouse HSC cultures through the use of physioxic culture conditions. Single-cell transcriptomic analysis confirmed inhibition of lineage-committed progenitor cells in physioxic cultures. Long-term physioxic expansion also afforded culture-based ex vivo HSC selection from whole bone marrow, spleen, and embryonic tissues. Furthermore, we provide evidence that HSC-selective ex vivo cultures deplete GvHD-causing T cells and that this approach can be combined with genotoxic-free antibody-based conditioning HSCT approaches. Our results offer a simple approach to improve PVA-based HSC cultures and the underlying molecular phenotype, as well as highlight the potential translational implications of selective HSC expansion systems for allogeneic HSCT.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 American Society of Hematology. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 24 Feb 2023 09:00 |
Last Modified: | 21 Jan 2025 18:08 |
Published Version: | https://doi.org/10.1182/bloodadvances.2023009668 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1182/bloodadvances.2023009668 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:196757 |
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Filename: bloodadvances.2023009668.pdf
Description: Physioxia improves the selectivity of hematopoietic stem cell expansion cultures