We recently corrected sickle cell disease in our knockin mouse model by reprogramming skin fibroblasts into iPS (induced Pluripotent Stem) cells, replacing the defective sickle beta-globin gene with a normal beta-globin gene, differentiating the corrected iPS cells into hematopoietic progenitors and transplanting these cells into irradiated sickle mouse recipients. The goal of the present proposal is to translate these results to human cells.
The specific aims are (1) to produce human iPS cells from skin biopsy samples of patients with sickle cell disease (2) to correct the sickle mutation in iPS cells derived from patients and (3) to differentiate corrected iPS cells into transplantable hematopoietic stem cells that produce normal erythroid cells.

Public Health Relevance

We recently corrected sickle cell disease in our knockin mouse model by reprogramming skin fibroblasts into iPS (induced Pluripotent Stem) cells, replacing the defective sickle beta-globin gene with a normal beta-globin gene, differentiating the corrected iPS cells into hematopoietic progenitors and transplanting these cells into irradiated sickle mouse recipients. The goal of the present proposal is to translate these results to human cells. These studies will provide a foundation for future clinical trials in humans.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057619-17
Application #
8604723
Study Section
Erythrocyte and Leukocyte Biology Study Section (ELB)
Program Officer
Qasba, Pankaj
Project Start
1996-09-30
Project End
2014-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
17
Fiscal Year
2014
Total Cost
$387,939
Indirect Cost
$123,134
Name
University of Alabama Birmingham
Department
Biochemistry
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Chang, Chia-Wei; Lai, Yi-Shin; Lamb Jr, Lawrence S et al. (2014) Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells. PLoS One 9:e97335
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