Genetic correction of ?-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice.

ABSTRACT: The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches. One such genetic disease is ?-thalassemia major (Cooley's anemia). This disease is caused by either a point mutation or the deletion of several nucleotides in the ?-globin gene, and it threatens the lives of millions of people in China. In the present study, we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his ?-globin gene. More importantly, we successfully corrected this genetic mutation in the ?-thalassemia iPSCs by homologous recombination. Furthermore, transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub-lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs. Moreover, the generation of human ?-globin could be detected in the mice transplanted with corrected iPSCs-derived hematopietic progenitors. Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC3317563 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature