Physioxia improves the selectivity of hematopoietic stem cell expansion cultures

Journal article

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.

Authors: Igarashi, KJ; Kucinski, I; Chan, YY; Tan, T-K; Khoo, HM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society of Hematology
• Journal: Blood Advances
• Volume: 7
• Issue: 14
• Pages: 3366–3377
• Publication date: 2023-02-21
• Acceptance date: 2023-01-30
• DOI: 10.1182/bloodadvances.2023009668
• EISSN: 2473-9537
• ISSN: 2473-9529
• Language: English
• Keywords: FFR