A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice
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-i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60464-3 |
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| author | Anna Konturek-Ciesla Qinyu Zhang Shabnam Kharazi David Bryder |
| author_facet | Anna Konturek-Ciesla Qinyu Zhang Shabnam Kharazi David Bryder |
| author_sort | Anna Konturek-Ciesla |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cfb8eb5cb01844219fbd05b6e3d8ba2f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cfb8eb5cb01844219fbd05b6e3d8ba2f2025-08-20T03:26:43ZengNature PortfolioNature Communications2041-17232025-06-0116111310.1038/s41467-025-60464-3A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in miceAnna Konturek-Ciesla0Qinyu Zhang1Shabnam Kharazi2David Bryder3Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Medical Faculty, Lund UniversityDivision of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Medical Faculty, Lund UniversityDivision of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Medical Faculty, Lund UniversityDivision of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Medical Faculty, Lund UniversityAbstract 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.https://doi.org/10.1038/s41467-025-60464-3 |
| spellingShingle | Anna Konturek-Ciesla Qinyu Zhang Shabnam Kharazi David Bryder A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice Nature Communications |
| title | A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice |
| title_full | A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice |
| title_fullStr | A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice |
| title_full_unstemmed | A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice |
| title_short | A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice |
| title_sort | non genotoxic stem cell therapy boosts lymphopoiesis and averts age related blood diseases in mice |
| url | https://doi.org/10.1038/s41467-025-60464-3 |
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