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Human Induced Pluripotent Stem Cells and the Modelling of Alzheimer’s Disease: The Human Brain Outside the Dish



Godwin Tong1, *, Pablo Izquierdo2, Rana Arham Raashid1
1 College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
2 Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London,  WC1E 6BT, United Kingdom


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© 2017 Tong et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom; Tel: +44 7415207196; E-mails: GXT545@bham.ac.uk, tongg@nsamr.ac.uk


Abstract

Background:

Neurodegenerative diseases like Alzheimer’s Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments.

Summary:

With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth. It is envisioned that iPSCs could be used as a powerful tool for neurodegenerative disease modelling and eventually be an unlimited source for cell replacement therapy. This paper provides an overview of; the contribution of iPSCs towards modeling and understanding AD pathogenesis, the novel human/mouse chimeric models in elucidating current AD pathogenesis hypotheses, the possible use of iPSCs in drug screening, and perspectives on possible future directions.

Key messages:

Human/mouse chimeric models using iPSCs to study AD offer much promise in better replicating AD pathology and can be further exploited to elucidate disease pathogenesis with regards to the neuroinflammation hypothesis of AD.

Keywords: Alzheimer’s Disease, Induced Pluripotent Stem Cells, AD Modelling, Human-mouse chimeric model, Microglia, Neuronal grafts, Neuroinflammation.