Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model
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 s...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-05-01
|
| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115000788 |
| _version_ | 1811283446321905664 |
|---|---|
| author | Tagan A. Griffin Hayley C. Anderson John H. Wolfe |
| author_facet | Tagan A. Griffin Hayley C. Anderson John H. Wolfe |
| author_sort | Tagan A. Griffin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T02:11:30Z |
| format | Article |
| id | doaj.art-8d4c748cdb3747fc87c6c4ee19663a21 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-13T02:11:30Z |
| publishDate | 2015-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-8d4c748cdb3747fc87c6c4ee19663a212022-12-22T03:07:17ZengElsevierStem Cell Reports2213-67112015-05-014583584610.1016/j.stemcr.2015.02.022Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse ModelTagan A. Griffin0Hayley C. Anderson1John H. Wolfe2Research Institute of the Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAResearch Institute of the Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAResearch Institute of the Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USANeural 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.http://www.sciencedirect.com/science/article/pii/S2213671115000788 |
| spellingShingle | Tagan A. Griffin Hayley C. Anderson John H. Wolfe Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model Stem Cell Reports |
| title | Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model |
| title_full | Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model |
| title_fullStr | Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model |
| title_full_unstemmed | Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model |
| title_short | Ex Vivo Gene Therapy Using Patient iPSC-Derived NSCs Reverses Pathology in the Brain of a Homologous Mouse Model |
| title_sort | ex vivo gene therapy using patient ipsc derived nscs reverses pathology in the brain of a homologous mouse model |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115000788 |
| work_keys_str_mv | AT taganagriffin exvivogenetherapyusingpatientipscderivednscsreversespathologyinthebrainofahomologousmousemodel AT hayleycanderson exvivogenetherapyusingpatientipscderivednscsreversespathologyinthebrainofahomologousmousemodel AT johnhwolfe exvivogenetherapyusingpatientipscderivednscsreversespathologyinthebrainofahomologousmousemodel |