Webinar Review: Understanding Human Brain Development and Disease: Organoids 101

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Understanding Human Brain Development and Disease: Organoids 101

Paola Arlotta, Harvard Professor of Stem Cell and Regenerative Biology
Harvard Brain Science Initiative

October 1, 2021

Charles MarchiniAnalysis by Charles Marchini:

This Webinar focuses on what cerebral organoids are, how they are made, the potential biomedical applications, and what needs to be done for research to continue moving forward.

Cerebral organoids are a way to study development and functionality of human brain cells. When using animal brains to model the human brain, replicating complex disorders such as autism and Alzheimer’s disease is difficult and results in big differences between the model and the human condition being studied. Cerebral organoids made of human cells have a huge potential in creating models that are more accurate for human diseases. The established pipeline for creating brain organoids is to take some skin or blood from humans and turn it into induced pluripotent stem cells, then use a bioreactor to bias the cells to develop into a particular type of structure. The result is an approximately 5mm diameter spheroid organoid made of a variety of human central nervous system cell types. Although developing cerebral organoids don’t look anything like a real developing human brain, there are some structural similarities such as distinct ventricle regions, synapses, and dendritic spines.

One way to study the activity of organoids is to insert an electrode to measure the spike rate of the neurons. Because the organoids contain retinal cells, a light can be shined on the organoid to produce a measurable change in the spike rate. Other methods used to study organoids include immunostaining and sequencing technology. Cerebral organoids have been shown to have the cellular diversity of a human brain, but to study the neural circuitry the correct anatomy is also needed. The cells need to be organized like a human brain otherwise the neural circuitry cannot represent human circuity such as the corticospinal tract and the retinohypothalamic tract. The way that organoids can be applied to medicine is by is using patient derived stem cells to build organoids to explore differences in cell types, molecular pathways, and therapeutic targets for diseases.

A major problem when it comes to growing organoids is that the tissue in the center of the organoid starts to decay because the fluid and nutrients in the bioreactor cannot reach it. Cerebral organoid researchers are trying to make vascularized organoids so that nutrients and fluid can get to the center of the organoids so they can grow larger. One way to study flow through biological tissue without destroying it is with magnetic resonance imaging (MRI). A research question I am looking into is how MRI can be used to image flow through organoids so we can understand the rate of fluid transfer between the outside and the inside of the organoid, and how vascularized organoids can allow blood to perfuse into the brain tissue.