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Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on β654-Thalassemia.
- Source :
- Stem Cells; Mar2024, Vol. 42 Issue 3, p278-289, 12p
- Publication Year :
- 2024
-
Abstract
- 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 (β<superscript>654-ER</superscript> mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C > T) mutation site and the 3ʹ splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β<superscript>654</superscript>-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β<superscript>654-ER</superscript> 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 β<superscript>654</superscript> 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 β<superscript>654-ER</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10665099
- Volume :
- 42
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Stem Cells
- Publication Type :
- Academic Journal
- Accession number :
- 176041319
- Full Text :
- https://doi.org/10.1093/stmcls/sxad096