Understanding the growth of human brains 

JGI Seed Corn Funding Project Blog 2023/24: James Armstrong

The human brain is a highly complex structure and an inaccessible organ to study, which has hampered our understanding of how the brain grows, becomes diseased, and responds to drugs. In the last ten years, a new method has been developed that uses stem cells to grow miniature brain tissues in the lab. These “brain organoids” have proven to be an incredibly useful tool for scientists studying the human brain. 

However, a well-known limitation of this tissue model is their unpredictable growth: within the same batch, some organoids will undergo typical neural development with large cortical buds (Figure 1A) while others will fail to produce these important structural features (Figure 1B). This Jean Golding Institute funded project sought to answer the question – can do seemingly identical stem cell cultures undergo such different growth? To this end, we aimed to track the growth of ~600 brain organoids over 20 days, then to use computer vision / machine learning methods to pick out key structural features that could be used to predict the tissue growth. 

Two brain organoids grown using different methods and showing the growth from day 3 to day 20
Figure 1. (A-B) Examples of two brain organoids, grown using the same methods, that were identical at day 3 but undergo very different growth. (C) An example of the images acquired during this project. 

This work was led by Dr James Armstrong, a Senior Research Fellow who runs a tissue engineering research group at Bristol Medical School (www.TheArmstrongGroup.co.uk). Members of his team (Martha Lavelle, Dr Aya Elghajiji, with help from Carolina Gaudenzi) have so far grown ~200 organoids, with another member of his team (Sammy Shorthouse) collecting microscopy images at ten intervals throughout the growth (Figure 1C). As expected, we saw tremendous variation in the growth of the brain organoids, in terms of their size, shape, and budding. Sammy has developed a program that takes these images and automatically processes them (indexing, identifying correct focal plane, centring, and cropping). He is now developing this script into a user-friendly “app”. For the next stages, Dr Qiang Liu in the Faculty of Engineering has been working with Sammy to develop computer vision methods that can pick out the key structural features of the organoids at the different stages of their growth. We are now growing the next batch of organoids and hope to reach the ~600 mark by the end of the summer. This should provide us with our target dataset, which should be large enough to start drawing links and making predictions of tissue growth. 


Contact details and links

If you wish to contact us about this study, please email james.armstrong@bristol.ac.uk