A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice

Anna Konturek-Ciesla, Qinyu Zhang, Shabnam Kharazi and David Bryder ()
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Anna Konturek-Ciesla: Lund University
Qinyu Zhang: Lund University
Shabnam Kharazi: Lund University
David Bryder: Lund University

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Hematopoietic stem cell (HSC) transplantation offers a cure for a variety of blood disorders, predominantly affecting the elderly; however, its application, especially in this demographic, is limited by treatment toxicity. In response, we employ a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated HSC depletion. While aging presents a significant barrier to effective HSC engraftment, optimizing HSC doses and non-genotoxic targeting methods greatly enhance the long-term multilineage activity of the transplanted cells. We demonstrate that young HSCs, once effectively engrafted in aged hosts, improve hematopoietic output and ameliorate age-compromised lymphopoiesis. This culminated in a strategy that robustly mitigates disease progression in a genetic model of myelodysplastic syndrome. These results suggest that non-genotoxic HSC transplantation could fundamentally change the clinical management of age-associated hematological disorders, offering a prophylactic tool to delay or even prevent their onset in elderly patients.

Date: 2025
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DOI: 10.1038/s41467-025-60464-3

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