IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60464-3.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60464-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60464-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sean J. Morrison & David T. Scadden, 2014. "The bone marrow niche for haematopoietic stem cells," Nature, Nature, vol. 505(7483), pages 327-334, January.
    2. 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.
    3. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yinghui Li & Mei He & Wenshan Zhang & Wei Liu & Hui Xu & Ming Yang & Hexiao Zhang & Haiwei Liang & Wenjing Li & Zhaozhao Wu & Weichao Fu & Shiqi Xu & Xiaolei Liu & Sibin Fan & Liwei Zhou & Chaoqun Wan, 2023. "Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Pasqualina Colella & Ruhi Sayana & Maria Valentina Suarez-Nieto & Jolanda Sarno & Kwamina Nyame & Jian Xiong & Luisa Natalia Pimentel Vera & Jessica Arozqueta Basurto & Marco Corbo & Anay Limaye & Kar, 2024. "CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    3. Tiago C. Luis & Nikolaos Barkas & Joana Carrelha & Alice Giustacchini & Stefania Mazzi & Ruggiero Norfo & Bishan Wu & Affaf Aliouat & Jose A. Guerrero & Alba Rodriguez-Meira & Tiphaine Bouriez-Jones &, 2023. "Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Trent D. Hall & Hyunjin Kim & Mahmoud Dabbah & Jacquelyn A. Myers & Jeremy Chase Crawford & Antonio Morales-Hernandez & Claire E. Caprio & Pramika Sriram & Emilia Kooienga & Marta Derecka & Esther A. , 2022. "Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Taichi Nakatani & Tatsuki Sugiyama & Yoshiki Omatsu & Hitomi Watanabe & Gen Kondoh & Takashi Nagasawa, 2023. "Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Narasaiah Kovuru & Makiko Mochizuki-Kashio & Theresa Menna & Greer Jeffrey & Yuning Hong & Young me Yoon & Zhe Zhang & Peter Kurre, 2024. "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Pradeep Ramalingam & Michael C. Gutkin & Michael G. Poulos & Taylor Tillery & Chelsea Doughty & Agatha Winiarski & Ana G. Freire & Shahin Rafii & David Redmond & Jason M. Butler, 2023. "Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Young-Woong Kim & Greta Zara & HyunJun Kang & Sergio Branciamore & Denis O’Meally & Yuxin Feng & Chia-Yi Kuan & Yingjun Luo & Michael S. Nelson & Alex B. Brummer & Russell Rockne & Zhen Bouman Chen & , 2022. "Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Tsu-Yi Su & Julia Hauenstein & Ece Somuncular & Özge Dumral & Elory Leonard & Charlotte Gustafsson & Efthymios Tzortzis & Aurora Forlani & Anne-Sofie Johansson & Hong Qian & Robert Månsson & Sidinh Lu, 2024. "Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Yang Ping Kuo & César Nombela-Arrieta & Oana Carja, 2024. "A theory of evolutionary dynamics on any complex population structure reveals stem cell niche architecture as a spatial suppressor of selection," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Runfeng Miao & Harim Chun & Xing Feng & Ana Cordeiro Gomes & Jungmin Choi & João P. Pereira, 2022. "Competition between hematopoietic stem and progenitor cells controls hematopoietic stem cell compartment size," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Qiang Zhao & Young-Min Han & Ping Song & Zhixue Liu & Zuyi Yuan & Ming-Hui Zou, 2022. "Endothelial cell-specific expression of serine/threonine kinase 11 modulates dendritic cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    13. Hung-Wei Cheng & Urs Mörbe & Mechthild Lütge & Céline Engetschwiler & Lucas Onder & Mario Novkovic & Cristina Gil-Cruz & Christian Perez-Shibayama & Thomas Hehlgans & Elke Scandella & Burkhard Ludewig, 2022. "Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. Yoshiki Omatsu & Shota Aiba & Tomonori Maeta & Kei Higaki & Kazunari Aoki & Hitomi Watanabe & Gen Kondoh & Riko Nishimura & Shu Takeda & Ung-il Chung & Takashi Nagasawa, 2022. "Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Tong Xing & Li-Juan Hu & Hong-Yan Zhao & Chen-Yuan Li & Zhen-Kun Wang & Meng-Zhu Shen & Zhong-Shi Lyu & Jing Wang & Yu Wang & Hao Jiang & Qian Jiang & Ying-Jun Chang & Xiao-Hui Zhang & Yuan Kong & Xia, 2024. "Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60464-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.