The safety and effectiveness of genetically corrected iPSCs derived from β-thalassaemia patients in nonmyeloablative β-thalassaemic mice

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-Hbb(tm2Unc)/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.