101. Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells.
- Author
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Yao Y, Nashun B, Zhou T, Qin L, Qin L, Zhao S, Xu J, Esteban MA, and Chen X
- Subjects
- Antigens, CD34 immunology, Cell Differentiation immunology, Cell Line, Deoxyribonucleases genetics, Deoxyribonucleases metabolism, Embryonic Stem Cells immunology, Flow Cytometry, Fluorescent Antibody Technique, Gene Silencing, Genetic Engineering, Genetic Vectors, Homologous Recombination, Humans, Induced Pluripotent Stem Cells immunology, Receptors, CCR5 immunology, Zinc Fingers, Antigens, CD34 metabolism, Embryonic Stem Cells metabolism, Induced Pluripotent Stem Cells metabolism, Receptors, CCR5 genetics
- Abstract
C-C chemokine receptor type 5 (CCR5) is a major co-receptor for the entry of human immunodeficiency virus type-1 (HIV-1) into target cells. Human hematopoietic stem cells (hHSCs) with naturally occurring CCR5 deletions (Δ32) or artificially disrupted CCR5 have shown potential for curing acquired immunodeficiency syndrome (AIDS). However, Δ32 donors are scarce, heterologous bone marrow transplantation is not exempt of risks, and genetic engineering of autologous hHSCs is not trivial. Here, we have disrupted the CCR5 locus of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) using specific zinc finger nucleases (ZFNs) combined with homologous recombination. The modified hESCs and hiPSCs retained pluripotent characteristics and could be differentiated in vitro into CD34(+) cells that formed all types of hematopoietic colonies. Our results suggest the potential of using patient-specific hHSCs derived from ZFN-modified hiPSCs for treating AIDS.
- Published
- 2012
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