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

doi:10.3390/biomedicines11041234

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

by

Sofia Carvalho

^1,2,3,4,

Juliana Inês Santos

^1,2,3,5,

Luciana Moreira

^1,2,3,

Mariana Gonçalves

^1,2,3,6

,

Hugo David

^1,2,3,5

,

Liliana Matos

^1,2,3,

Marisa Encarnação

^1,2,3

,

Sandra Alves

^1,2,3,†

and

Maria Francisca Coutinho

^1,2,3,*,†

¹

Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal

²

Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal

³

Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal

⁴

Faculty of Pharmacy, University of Coimbra, Polo das Ciências da Saúde, Azinhaga de SantaComba, 3000-548 Coimbra, Portugal

⁵

Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal

⁶

Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Biomedicines 2023, 11(4), 1234; https://doi.org/10.3390/biomedicines11041234

Submission received: 8 March 2023 / Revised: 18 April 2023 / Accepted: 19 April 2023 / Published: 21 April 2023

(This article belongs to the Special Issue Molecular Mechanisms in Lysosomal Storage Diseases: From Pathogenesis to Therapeutic Strategies 2.0)

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Abstract

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.

Keywords: mucopolysaccharidoses; disease modeling; in vitro models; induced pluripotent stem cells (iPSCs); dental pulp stem cells (DPSCs)

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MDPI and ACS Style

Carvalho, S.; Santos, J.I.; Moreira, L.; Gonçalves, M.; David, H.; Matos, L.; Encarnação, M.; Alves, S.; Coutinho, M.F. Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses. Biomedicines 2023, 11, 1234. https://doi.org/10.3390/biomedicines11041234

AMA Style

Carvalho S, Santos JI, Moreira L, Gonçalves M, David H, Matos L, Encarnação M, Alves S, Coutinho MF. Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses. Biomedicines. 2023; 11(4):1234. https://doi.org/10.3390/biomedicines11041234

Chicago/Turabian Style

Carvalho, Sofia, Juliana Inês Santos, Luciana Moreira, Mariana Gonçalves, Hugo David, Liliana Matos, Marisa Encarnação, Sandra Alves, and Maria Francisca Coutinho. 2023. "Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses" Biomedicines 11, no. 4: 1234. https://doi.org/10.3390/biomedicines11041234

APA Style

Carvalho, S., Santos, J. I., Moreira, L., Gonçalves, M., David, H., Matos, L., Encarnação, M., Alves, S., & Coutinho, M. F. (2023). Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses. Biomedicines, 11(4), 1234. https://doi.org/10.3390/biomedicines11041234

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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

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