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Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders;...

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Autores principales: Carvalho, Sofia, Santos, Juliana Inês, Moreira, Luciana, Gonçalves, Mariana, David, Hugo, Matos, Liliana, Encarnação, Marisa, Alves, Sandra, Coutinho, Maria Francisca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135551/
https://www.ncbi.nlm.nih.gov/pubmed/37189853
http://dx.doi.org/10.3390/biomedicines11041234
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author Carvalho, Sofia
Santos, Juliana Inês
Moreira, Luciana
Gonçalves, Mariana
David, Hugo
Matos, Liliana
Encarnação, Marisa
Alves, Sandra
Coutinho, Maria Francisca
author_facet Carvalho, Sofia
Santos, Juliana Inês
Moreira, Luciana
Gonçalves, Mariana
David, Hugo
Matos, Liliana
Encarnação, Marisa
Alves, Sandra
Coutinho, Maria Francisca
author_sort Carvalho, Sofia
collection PubMed
description Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.
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spelling pubmed-101355512023-04-28 Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses Carvalho, Sofia Santos, Juliana Inês Moreira, Luciana Gonçalves, Mariana David, Hugo Matos, Liliana Encarnação, Marisa Alves, Sandra Coutinho, Maria Francisca Biomedicines Review Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures. MDPI 2023-04-21 /pmc/articles/PMC10135551/ /pubmed/37189853 http://dx.doi.org/10.3390/biomedicines11041234 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Carvalho, Sofia
Santos, Juliana Inês
Moreira, Luciana
Gonçalves, Mariana
David, Hugo
Matos, Liliana
Encarnação, Marisa
Alves, Sandra
Coutinho, Maria Francisca
Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
title Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
title_full Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
title_fullStr Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
title_full_unstemmed Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
title_short Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
title_sort neurological disease modeling using pluripotent and multipotent stem cells: a key step towards understanding and treating mucopolysaccharidoses
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135551/
https://www.ncbi.nlm.nih.gov/pubmed/37189853
http://dx.doi.org/10.3390/biomedicines11041234
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