title: Therapeutic effects of induced pluripotent stem cells in chimeric mice with β-thalassemia.
abstract: Although β-thalassemia is one of the most common human genetic diseases, there is still no effective treatment other than bone marrow transplantation. Induced pluripotent stem cells have been considered good candidates for the future repair or replacement of malfunctioning organs. As a basis for developing transgenic induced pluripotent stem cell therapies for thalassemia, β(654) induced pluripotent stem cells from a β(654) -thalassemia mouse transduced with the normal human β-globin gene, and the induced pluripotent stem cells with an erythroid-expressing reporter GFP were used to produce chimeric mice. Using these chimera models, we investigated changes in various pathological indices including hematologic parameters and tissue pathology. Our data showed that when the chimerism of β(654) induced pluripotent stem cells with the normal human β-globin gene in β(654) mice is over 30%, the pathology of anemia appeared to be reversed, while chimerism ranging from 8% to 16% provided little improvement in the typical β-thalassemia phenotype. Effective alleviation of thalassemia-related phenotypes was observed when chimerism with the induced pluripotent stem cells owning the erythroid-expressing reporter GFP in β(654) mouse was greater than 10%. Thus, 10% or more expression of the exogenous normal β-globin gene reduces the degree of anemia in our β-thalassemia mouse model, whereas treatment with β(654) induced pluripotent stem cells which had the normal human β-globin gene had stable therapeutic effects but in a more dose-dependent manner.
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Insitute of Medical Science, School of Medicine, Shanghai Jiaotong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China.
authors.forename: Guanheng
authors.initials: G
authors.lastname: Yang
authors.affiliation: Insitute of Medical Science, School of Medicine, Shanghai Jiaotong University.
authors.forename: Wansheng
authors.initials: W
authors.lastname: Shi
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Insitute of Medical Science, School of Medicine, Shanghai Jiaotong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China.
authors.forename: Xingyin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China.
authors.forename: Xinbing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China.
authors.forename: Zhaorui
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University Insitute of Medical Science, School of Medicine, Shanghai Jiaotong University Key Laboratory of Embryo Molecular Biology, Ministry of Health of China and Shanghai Laboratory of Embryo and Reproduction Engineering, China fzeng@sjtu.edu.cn.
authors.forename: Fanyi
authors.initials: F
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002678:Chimera; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000235:genetics / Q000473:pathology* / Q000628:therapy*