If Human Brain Organoids Are the Answer to Understanding Dementia, What Are the Questions?

Abstract

Because our beliefs regarding our individuality, autonomy, and personhood are intimately bound up with our brains, there is a public fascination with cerebral organoids, the "mini-brain," the "brain in a dish". At the same time, the ethical issues around organoids are only now being explored. What are the prospects of using human cerebral organoids to better understand, treat, or prevent dementia? Will human organoids represent an improvement on the current, less-than-satisfactory, animal models? When considering these questions, two major issues arise. One is the general challenge associated with using any stem cell-generated preparation for in vitro modelling (challenges amplified when using organoids compared with simpler cell culture systems). The other relates to complexities associated with defining and understanding what we mean by the term "dementia." We discuss 10 puzzles, issues, and stumbling blocks to watch for in the quest to model "dementia in a dish." ; The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Australian Dementia Stem Cell Consortium has received generous start-up travel grants from the Australian NHMRC National Institute for Dementia Research. Authors have been supported by Dementia Australia Research Foundation, Yulgilbar Alzheimer's Research Program, DHB Foundation (AP), Brain Foundation (DH, AP), the C.F. Leung Memorial Trust (AP), the University of Melbourne (AP) and Operational Infrastructure Support from the Victorian Government (DH, AP), Monash University (AG), JO and JR Wicking Trust (Equity Trustees) (ALC and AEK), University of Sydney (MV), and generous gifts from the Sinclair, Smith and Jolly families (MV). AEK is supported by a National Health and Medical Research Council (NHMRC) of Australia Boosting Dementia Research Leadership Fellowship (APP1136913). AG is supported by a NHMRC-ARC Dementia Research Development Fellowship (GNT1097461). AP is supported by an ARC Future Fellowship ...