Cargando…
Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of motor neurons. Currently, there is no effective therapy for ALS. Stem cell transplantation is a potential therapeutic strategy for ALS, and the reprogramming of adult somatic cells into induced p...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869354/ https://www.ncbi.nlm.nih.gov/pubmed/24006477 http://dx.doi.org/10.1093/hmg/ddt425 |
_version_ | 1782296560186425344 |
---|---|
author | Nizzardo, Monica Simone, Chiara Rizzo, Federica Ruggieri, Margherita Salani, Sabrina Riboldi, Giulietta Faravelli, Irene Zanetta, Chiara Bresolin, Nereo Comi, Giacomo P. Corti, Stefania |
author_facet | Nizzardo, Monica Simone, Chiara Rizzo, Federica Ruggieri, Margherita Salani, Sabrina Riboldi, Giulietta Faravelli, Irene Zanetta, Chiara Bresolin, Nereo Comi, Giacomo P. Corti, Stefania |
author_sort | Nizzardo, Monica |
collection | PubMed |
description | Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of motor neurons. Currently, there is no effective therapy for ALS. Stem cell transplantation is a potential therapeutic strategy for ALS, and the reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) represents a novel cell source. In this study, we isolated a specific neural stem cell (NSC) population from human iPSCs based on high aldehyde dehydrogenase activity, low side scatter and integrin VLA4 positivity. We assessed the therapeutic effects of these NSCs on the phenotype of ALS mice after intrathecal or intravenous injections. Transplanted NSCs migrated and engrafted into the central nervous system via both routes of injection. Compared with control ALS, treated ALS mice exhibited improved neuromuscular function and motor unit pathology and significantly increased life span, in particular with the systemic administration of NSCs (15%). These positive effects are linked to multiple mechanisms, including production of neurotrophic factors and reduction of micro- and macrogliosis. NSCs induced a decrease in astrocyte number through the activation of the vanilloid receptor TRPV1. We conclude that minimally invasive injections of iPSC-derived NSCs can exert a therapeutic effect in ALS. This study contributes to advancements in iPSC-mediated approaches for treating ALS and other neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-3869354 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38693542013-12-20 Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model Nizzardo, Monica Simone, Chiara Rizzo, Federica Ruggieri, Margherita Salani, Sabrina Riboldi, Giulietta Faravelli, Irene Zanetta, Chiara Bresolin, Nereo Comi, Giacomo P. Corti, Stefania Hum Mol Genet Articles Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of motor neurons. Currently, there is no effective therapy for ALS. Stem cell transplantation is a potential therapeutic strategy for ALS, and the reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) represents a novel cell source. In this study, we isolated a specific neural stem cell (NSC) population from human iPSCs based on high aldehyde dehydrogenase activity, low side scatter and integrin VLA4 positivity. We assessed the therapeutic effects of these NSCs on the phenotype of ALS mice after intrathecal or intravenous injections. Transplanted NSCs migrated and engrafted into the central nervous system via both routes of injection. Compared with control ALS, treated ALS mice exhibited improved neuromuscular function and motor unit pathology and significantly increased life span, in particular with the systemic administration of NSCs (15%). These positive effects are linked to multiple mechanisms, including production of neurotrophic factors and reduction of micro- and macrogliosis. NSCs induced a decrease in astrocyte number through the activation of the vanilloid receptor TRPV1. We conclude that minimally invasive injections of iPSC-derived NSCs can exert a therapeutic effect in ALS. This study contributes to advancements in iPSC-mediated approaches for treating ALS and other neurodegenerative diseases. Oxford University Press 2014-01-15 2013-09-04 /pmc/articles/PMC3869354/ /pubmed/24006477 http://dx.doi.org/10.1093/hmg/ddt425 Text en © The Author 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Articles Nizzardo, Monica Simone, Chiara Rizzo, Federica Ruggieri, Margherita Salani, Sabrina Riboldi, Giulietta Faravelli, Irene Zanetta, Chiara Bresolin, Nereo Comi, Giacomo P. Corti, Stefania Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
title | Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
title_full | Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
title_fullStr | Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
title_full_unstemmed | Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
title_short | Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
title_sort | minimally invasive transplantation of ipsc-derived aldhhissclovla4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869354/ https://www.ncbi.nlm.nih.gov/pubmed/24006477 http://dx.doi.org/10.1093/hmg/ddt425 |
work_keys_str_mv | AT nizzardomonica minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT simonechiara minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT rizzofederica minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT ruggierimargherita minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT salanisabrina minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT riboldigiulietta minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT faravelliirene minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT zanettachiara minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT bresolinnereo minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT comigiacomop minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel AT cortistefania minimallyinvasivetransplantationofipscderivedaldhhissclovla4neuralstemcellseffectivelyimprovesthephenotypeofanamyotrophiclateralsclerosismodel |