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Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development
Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141323/ https://www.ncbi.nlm.nih.gov/pubmed/32121121 http://dx.doi.org/10.3390/jcm9030644 |
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author | Benetó, Noelia Cozar, Monica Castilla-Vallmanya, Laura Zetterdahl, Oskar G. Sacultanu, Madalina Segur-Bailach, Eulalia García-Morant, María Ribes, Antonia Ahlenius, Henrik Grinberg, Daniel Vilageliu, Lluïsa Canals, Isaac |
author_facet | Benetó, Noelia Cozar, Monica Castilla-Vallmanya, Laura Zetterdahl, Oskar G. Sacultanu, Madalina Segur-Bailach, Eulalia García-Morant, María Ribes, Antonia Ahlenius, Henrik Grinberg, Daniel Vilageliu, Lluïsa Canals, Isaac |
author_sort | Benetó, Noelia |
collection | PubMed |
description | Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present obvious limitations. Induced pluripotent stem cells (iPSCs) are an efficient way to model human diseases in vitro. Recently developed transcription factor-based differentiation protocols allow fast and efficient conversion of iPSCs into the cell type of interest. By applying these protocols, we have generated new neuronal and astrocytic models of Sanfilippo syndrome using our previously established disease iPSC lines. Moreover, our neuronal model exhibits disease-specific molecular phenotypes, such as increase in lysosomes and heparan sulfate. Lastly, we tested an experimental, siRNA-based treatment previously shown to be successful in patients’ fibroblasts and demonstrated its lack of efficacy in neurons. Our findings highlight the need to use relevant human cellular models to test therapeutic interventions and shows the applicability of our neuronal and astrocytic models of Sanfilippo syndrome for future studies on disease mechanisms and drug development. |
format | Online Article Text |
id | pubmed-7141323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71413232020-04-10 Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development Benetó, Noelia Cozar, Monica Castilla-Vallmanya, Laura Zetterdahl, Oskar G. Sacultanu, Madalina Segur-Bailach, Eulalia García-Morant, María Ribes, Antonia Ahlenius, Henrik Grinberg, Daniel Vilageliu, Lluïsa Canals, Isaac J Clin Med Article Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present obvious limitations. Induced pluripotent stem cells (iPSCs) are an efficient way to model human diseases in vitro. Recently developed transcription factor-based differentiation protocols allow fast and efficient conversion of iPSCs into the cell type of interest. By applying these protocols, we have generated new neuronal and astrocytic models of Sanfilippo syndrome using our previously established disease iPSC lines. Moreover, our neuronal model exhibits disease-specific molecular phenotypes, such as increase in lysosomes and heparan sulfate. Lastly, we tested an experimental, siRNA-based treatment previously shown to be successful in patients’ fibroblasts and demonstrated its lack of efficacy in neurons. Our findings highlight the need to use relevant human cellular models to test therapeutic interventions and shows the applicability of our neuronal and astrocytic models of Sanfilippo syndrome for future studies on disease mechanisms and drug development. MDPI 2020-02-28 /pmc/articles/PMC7141323/ /pubmed/32121121 http://dx.doi.org/10.3390/jcm9030644 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Benetó, Noelia Cozar, Monica Castilla-Vallmanya, Laura Zetterdahl, Oskar G. Sacultanu, Madalina Segur-Bailach, Eulalia García-Morant, María Ribes, Antonia Ahlenius, Henrik Grinberg, Daniel Vilageliu, Lluïsa Canals, Isaac Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development |
title | Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development |
title_full | Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development |
title_fullStr | Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development |
title_full_unstemmed | Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development |
title_short | Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development |
title_sort | neuronal and astrocytic differentiation from sanfilippo c syndrome ipscs for disease modeling and drug development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141323/ https://www.ncbi.nlm.nih.gov/pubmed/32121121 http://dx.doi.org/10.3390/jcm9030644 |
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