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

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  • Anna Konturek-Ciesla

    (Lund University
    ETH Zurich)

  • Qinyu Zhang

    (Lund University)

  • Shabnam Kharazi

    (Lund University)

  • David Bryder

    (Lund University)

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.

Suggested Citation

  • Anna Konturek-Ciesla & Qinyu Zhang & Shabnam Kharazi & David Bryder, 2025. "A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60464-3
    DOI: 10.1038/s41467-025-60464-3
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    1. Adam C. Wilkinson & Reiko Ishida & Misako Kikuchi & Kazuhiro Sudo & Maiko Morita & Ralph Valentine Crisostomo & Ryo Yamamoto & Kyle M. Loh & Yukio Nakamura & Motoo Watanabe & Hiromitsu Nakauchi & Sato, 2019. "Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation," Nature, Nature, vol. 571(7763), pages 117-121, July.
    2. Sean J. Morrison & David T. Scadden, 2014. "The bone marrow niche for haematopoietic stem cells," Nature, Nature, vol. 505(7483), pages 327-334, January.
    3. Jason B. Ross & Lara M. Myers & Joseph J. Noh & Madison M. Collins & Aaron B. Carmody & Ronald J. Messer & Erica Dhuey & Kim J. Hasenkrug & Irving L. Weissman, 2024. "Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity," Nature, Nature, vol. 628(8006), pages 162-170, April.
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