Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on β654-Thalassemia
© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com..
β-thalassemia is an inherited blood disease caused by reduced or inadequate β-globin synthesis due to β-globin gene mutation. Our previous study developed a gene-edited mice model (β654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C > T) mutation site and the 3' splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β654-ER mice on β-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted β654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the β-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from β654-ER mice on β-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Stem cells (Dayton, Ohio) - 42(2024), 3 vom: 14. März, Seite 278-289 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lu, Dan [VerfasserIn] |
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| Links: |
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| Themen: |
β-thalassemia |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/stmcls/sxad096 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a β-thalassemia is an inherited blood disease caused by reduced or inadequate β-globin synthesis due to β-globin gene mutation. Our previous study developed a gene-edited mice model (β654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C > T) mutation site and the 3' splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β654-ER mice on β-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted β654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the β-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from β654-ER mice on β-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future | ||
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| 700 | 1 | |a Yang, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Dali |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Yitao |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Fanyi |e verfasserin |4 aut | |
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