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Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons

Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection...

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Autores principales: Mollinari, Cristiana, De Dominicis, Chiara, Lupacchini, Leonardo, Sansone, Luigi, Caprini, Davide, Casciola, Carlo Massimo, Wang, Ying, Zhao, Jian, Fini, Massimo, Russo, Matteo, Garaci, Enrico, Merlo, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879457/
https://www.ncbi.nlm.nih.gov/pubmed/35216271
http://dx.doi.org/10.3390/ijms23042147
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author Mollinari, Cristiana
De Dominicis, Chiara
Lupacchini, Leonardo
Sansone, Luigi
Caprini, Davide
Casciola, Carlo Massimo
Wang, Ying
Zhao, Jian
Fini, Massimo
Russo, Matteo
Garaci, Enrico
Merlo, Daniela
author_facet Mollinari, Cristiana
De Dominicis, Chiara
Lupacchini, Leonardo
Sansone, Luigi
Caprini, Davide
Casciola, Carlo Massimo
Wang, Ying
Zhao, Jian
Fini, Massimo
Russo, Matteo
Garaci, Enrico
Merlo, Daniela
author_sort Mollinari, Cristiana
collection PubMed
description Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases. We found that FAD fibroblasts have a reduced efficiency of reprogramming, and converted ciNs show a less complex neuronal network. In addition, ciNs from patients show misfolded protein accumulation and mitochondria ultrastructural abnormalities, biomarkers commonly associated with neurodegeneration. Moreover, for the first time, we show that microfluidic technology, in combination with chemical reprogramming, enables on-chip examination of disease pathological processes and may have important applications in diagnosis. In conclusion, ciNs on microfluidic devices represent a small-scale, non-invasive and cost-effective high-throughput tool for protein misfolding disease diagnosis and may be useful for new biomarker discovery, disease mechanism studies and design of personalised therapies.
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spelling pubmed-88794572022-02-26 Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons Mollinari, Cristiana De Dominicis, Chiara Lupacchini, Leonardo Sansone, Luigi Caprini, Davide Casciola, Carlo Massimo Wang, Ying Zhao, Jian Fini, Massimo Russo, Matteo Garaci, Enrico Merlo, Daniela Int J Mol Sci Article Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases. We found that FAD fibroblasts have a reduced efficiency of reprogramming, and converted ciNs show a less complex neuronal network. In addition, ciNs from patients show misfolded protein accumulation and mitochondria ultrastructural abnormalities, biomarkers commonly associated with neurodegeneration. Moreover, for the first time, we show that microfluidic technology, in combination with chemical reprogramming, enables on-chip examination of disease pathological processes and may have important applications in diagnosis. In conclusion, ciNs on microfluidic devices represent a small-scale, non-invasive and cost-effective high-throughput tool for protein misfolding disease diagnosis and may be useful for new biomarker discovery, disease mechanism studies and design of personalised therapies. MDPI 2022-02-15 /pmc/articles/PMC8879457/ /pubmed/35216271 http://dx.doi.org/10.3390/ijms23042147 Text en © 2022 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 Article
Mollinari, Cristiana
De Dominicis, Chiara
Lupacchini, Leonardo
Sansone, Luigi
Caprini, Davide
Casciola, Carlo Massimo
Wang, Ying
Zhao, Jian
Fini, Massimo
Russo, Matteo
Garaci, Enrico
Merlo, Daniela
Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons
title Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons
title_full Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons
title_fullStr Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons
title_full_unstemmed Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons
title_short Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons
title_sort detection of pathological markers of neurodegenerative diseases following microfluidic direct conversion of patient fibroblasts into neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879457/
https://www.ncbi.nlm.nih.gov/pubmed/35216271
http://dx.doi.org/10.3390/ijms23042147
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