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

Authors :
Cristiana Mollinari
Chiara De Dominicis
Leonardo Lupacchini
Luigi Sansone
Davide Caprini
Carlo Massimo Casciola
Ying Wang
Jian Zhao
Massimo Fini
Matteo Russo
Enrico Garaci
Daniela Merlo
Source :
International Journal of Molecular Sciences, Vol 23, Iss 4, p 2147 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
4
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.8032faf1b0d419a9e23e5babea57fb4
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms23042147