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

Author:

Ooi Lezanne12ORCID,Dottori Mirella1345,Cook Anthony L.6ORCID,Engel Martin12ORCID,Gautam Vini7,Grubman Alexandra8910,Hernández Damián41112,King Anna E.6ORCID,Maksour Simon13,Targa Dias Anastacio Helena12,Balez Rachelle12,Pébay Alice41112,Pouton Colin13,Valenzuela Michael14,White Anthony15,Williamson Robert1617

Affiliation:

1. Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia

2. School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia

3. School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia

4. Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Victoria, Australia

5. Department of Biomedical Engineering, University of Melbourne, Parkville, Victoria, Australia

6. Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia

7. John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia

8. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia

9. Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia

10. Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia

11. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne, Victoria, Australia

12. Department of Surgery, University of Melbourne, Parkville, Victoria, Australia

13. Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

14. Regenerative Neuroscience Group, Brain and Mind Centre and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

15. Queensland Institute of Medical Research Berghofer, Brisbane, Queensland, Australia

16. Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

17. Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia

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.”

Funder

Australian Research Council

National Health and Medical Research Council

Publisher

SAGE Publications

Subject

Clinical Neurology,General Neuroscience

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