Modelling neurodegenerative diseases in vitro: recent advances in 3D iPSC technologies

Siney, E.J., Kurbatskaya, K., Chatterjee, S. ORCID: 0000-0002-2506-1278, Prasannan, P., Mudher, A. and Willaime-Morawek, S., 2018. Modelling neurodegenerative diseases in vitro: recent advances in 3D iPSC technologies. AIMS Cell and Tissue Engineering, 2 (1), pp. 1-23. ISSN 2574-0105

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Abstract

The discovery of induced pluripotent stem cells (iPSC) 12 years ago has fostered the development of innovative patient-derived in vitro models for better understanding of disease mechanisms. This is particularly relevant to neurodegenerative diseases, where availability of live human brain tissue for research is limited and post-mortem interval changes influence readouts from autopsy-derived human tissue. Hundreds of iPSC lines have now been prepared and banked, thanks to several large scale initiatives and cell banks. Patient- or engineered iPSC-derived neural models are now being used to recapitulate cellular and molecular aspects of a variety of neurodegenerative diseases, including early and pre-clinical disease stages. The broad relevance of these models derives from the availability of a variety of differentiation protocols to generate disease-specific cell types and the manipulation to either introduce or correct disease-relevant genetic modifications. Moreover, the use of chemical and physical three-dimensional (3D) matrices improves control over the extracellular environment and cellular organization of the models. These iPSC-derived neural models can be utilised to identify target proteins and, importantly, provide high-throughput screening for drug discovery. Choosing Alzheimer’s disease (AD) as an example, this review describes 3D iPSC-derived neural models and their advantages and limitations. There is now a requirement to fully characterise and validate these 3D iPSC-derived neural models as a viable research tool that is capable of complementing animal models of neurodegeneration and live human brain tissue. With further optimization of differentiation, maturation and aging protocols, as well as the 3D cellular organisation and extracellular matrix to recapitulate more closely, the molecular extracellular-environment of the human brain, 3D iPSC-derived models have the potential to deliver new knowledge, enable discovery of novel disease mechanisms and identify new therapeutic targets for neurodegenerative diseases.

Item Type: Journal article
Publication Title: AIMS Cell and Tissue Engineering
Creators: Siney, E.J., Kurbatskaya, K., Chatterjee, S., Prasannan, P., Mudher, A. and Willaime-Morawek, S.
Publisher: American Institute of Mathematical Sciences (AIMS)
Date: 2018
Volume: 2
Number: 1
ISSN: 2574-0105
Identifiers:
NumberType
10.3934/celltissue.2018.1.1DOI
1394961Other
Rights: © 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 16 Dec 2020 16:06
Last Modified: 16 Dec 2020 16:06
URI: http://irep.ntu.ac.uk/id/eprint/41887

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