Portal de Periódicos da CAPES

Physioxia improves the selectivity of hematopoietic stem cell expansion cultures

2023; Elsevier BV; Volume: 7; Issue: 14 Linguagem: Inglês

10.1182/bloodadvances.2023009668

2473-9537

Kyomi J. Igarashi, Iwo Kuciński, Yan Yi Chan, Tze-Kai Tan, Hwei Minn Khoo, David Kealy, Joydeep Bhadury, Ian Hsu, Pui Yan Ho, Kouta Niizuma, John W. Hickey, Garry P. Nolan, Katherine S. Bridge, Agnieszka Czechowicz, Berthold Göttgens, Hiromitsu Nakauchi, Adam C. Wilkinson,

T-cell and B-cell Immunology

Hematopoietic stem cells (HSCs) are a rare type of hematopoietic cell that can entirely reconstitute the blood and immune system after transplantation. Allogeneic HSC transplantation (HSCT) is used clinically as a curative therapy for a range of hematolymphoid diseases; however, it remains a high-risk therapy because of its potential side effects, including poor graft function and graft-versus-host disease (GVHD). Ex vivo HSC expansion has been suggested as an approach to improve hematopoietic reconstitution in low-cell dose grafts. Here, we demonstrate that the selectivity of polyvinyl alcohol (PVA)-based mouse HSC cultures can be improved using physioxic culture conditions. Single-cell transcriptomic analysis helped confirm the 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, and highlight the potential translational implications of selective HSC expansion systems for allogeneic HSCT.