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bioRxiv · 10.1101/2025.09.10.675303

Polymer-based culture system enables expansion of human haematopoietic stem and progenitor cells while preserving ageing-associated transcriptional programs

Symeonidou, V.·Bond, L.·Giannelou, E.·Bozhilov, Y.·Rubio-Lara, J.·Wilkinson, A. C.·Vassiliou, G. S.
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Abstract

The global rise in ageing populations is driving an increase in age-associated diseases, including haematological malignancies such as myelodysplastic syndromes and acute myeloid leukaemia. A major challenge in addressing this burden is the lack of experimental systems that enable mechanistic studies and therapeutic screening in ageing haematopoiesis. Here, we evaluate a polymer-based ex vivo culture platform for studying human haematopoietic stem and progenitor cells (HSPCs) in the context of ageing. Using CD34+ cells from cord blood, bone marrow and peripheral blood from different age groups, we show that this culture system enables robust expansion of HSPCs while preserving age-associated transcriptional programs. Single-cell RNA sequencing revealed enrichment of key progenitor populations with consistent transcriptional identities across donors. Importantly, expanded HSPCs from older individuals retained ageing-associated signatures, such as upregulation of inflammatory pathways. These findings demonstrate that our polymer-based expansion system enables robust modelling of ageing haematopoiesis and provide a single cell transcriptional landscape of this ageing model. We envision that this system could provide a versatile platform for mechanistic studies and pharmacological testing, addressing a critical gap in experimental frameworks for age-related haematological disease research.

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Symeonidou, V., Bond, L., Giannelou, E., Bozhilov, Y., Rubio-Lara, J., Wilkinson, A. C., Vassiliou, G. S.. 2025-09-10. Polymer-based culture system enables expansion of human haematopoietic stem and progenitor cells while preserving ageing-associated transcriptional programs. https://doi.org/10.1101/2025.09.10.675303

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