Abstract |
Neural stem cell (NSC) transplantation is a promising strategy for delivering therapeutic proteins in the brain. We evaluated a complete process of ex vivo gene therapy using human induced pluripotent stem cell (iPSC)-derived NSC transplants in a well-characterized mouse model of a human lysosomal storage disease, Sly disease. Human Sly disease fibroblasts were reprogrammed into iPSCs, differentiated into a stable and expandable population of NSCs, genetically corrected with a transposon vector, and assessed for engraftment in NOD/SCID mice. Following neonatal intraventricular transplantation, the NSCs engraft along the rostrocaudal axis of the CNS primarily within white matter tracts and survive for at least 4 months. Genetically corrected iPSC-NSCs transplanted post-symptomatically into the striatum of adult Sly disease mice reversed neuropathology in a zone surrounding the grafts, while control mock-corrected grafts did not. The results demonstrate the potential for ex vivo gene therapy in the brain using human NSCs from autologous, non-neural tissues.
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Authors | Tagan A Griffin, Hayley C Anderson, John H Wolfe |
Journal | Stem cell reports
(Stem Cell Reports)
Vol. 4
Issue 5
Pg. 835-46
(May 12 2015)
ISSN: 2213-6711 [Electronic] United States |
PMID | 25866157
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Adult
- Animals
- Brain
(pathology)
- Cell Differentiation
- Cells, Cultured
- Cellular Reprogramming
- Dependovirus
(genetics)
- Disease Models, Animal
- Female
- Genetic Therapy
- Humans
- Karyotyping
- Mice
- Mice, Inbred C57BL
- Mice, Inbred NOD
- Mice, SCID
- Mucopolysaccharidosis VII
(therapy)
- Neural Stem Cells
(cytology, metabolism, transplantation)
- Pluripotent Stem Cells
(cytology)
- Transcription Factors
(genetics, metabolism)
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