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

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.