Author:
Xian Yexing,Xie Yingjun,Song Bing,Ou Zhanhui,Ouyang Shuming,Xie Yuhuan,Yang Yi,Xiong Zeyu,Li Haoxian,Sun Xiaofang
Abstract
Abstract
Background
β-Thalassaemia is a clinically common cause of hereditary haemolytic anaemia stemming from mutations in important functional regions of the β-globin gene. The rapid development of gene editing technology and induced pluripotent stem cell (iPSC)-derived haematopoietic stem cell (HSC) transplantation has provided new methods for curing this disease.
Methods
Genetically corrected β-thalassaemia (homozygous 41/42 deletion) iPSCs that were previously established in our laboratory were induced to differentiate into HSCs, which were transplanted into a mouse model of IVS2–654 β-thalassaemia (B6;129P2-Hbbtm2Unc/J mice) after administration of an appropriate nonmyeloablative conditioning regimen. We also investigated the safety of this method by detecting the incidence of tumour formation in these mice after transplantation.
Results
The combination of 25 mg/kg busulfan and 50 mg/(kg day) cyclophosphamide is an ideal nonmyeloablative protocol before transplantation. Genetically corrected β-thalassaemic HSCs survived and differentiated in nonmyeloablated thalassaemia mice. No tumour formation was observed in the mice for 10 weeks after transplantation.
Conclusion
Our study provides evidence that the transplantation of genetically corrected, patient-specific iPSCs could be used to cure genetic diseases, such as β-thalassaemia major.
Funder
the Science and Information Technology of Guangzhou Key Project
the Youth Project by Education of Guangdong Province
the Guangdong Province Science and Technology Project
Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)
Cited by
5 articles.
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