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

Konturek-Ciesla, Anna LU ; Zhang, Qinyu LU orcid ; Kharazi, Shabnam LU and Bryder, David LU (2025) In Nature Communications 16(1).
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... (More)

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.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
16
issue
1
article number
5129
publisher
Nature Publishing Group
external identifiers
  • pmid:40456713
  • scopus:105007095556
ISSN
2041-1723
DOI
10.1038/s41467-025-60464-3
language
English
LU publication?
yes
id
948de61c-ffce-44c0-91d0-c95550c09f0f
date added to LUP
2025-07-14 09:49:49
date last changed
2025-07-15 03:28:21
@article{948de61c-ffce-44c0-91d0-c95550c09f0f,
  abstract     = {{<p>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.</p>}},
  author       = {{Konturek-Ciesla, Anna and Zhang, Qinyu and Kharazi, Shabnam and Bryder, David}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-60464-3}},
  doi          = {{10.1038/s41467-025-60464-3}},
  volume       = {{16}},
  year         = {{2025}},
}