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Stem Cells in Focus

Modeling Human Biology and Organoids: A Big Impact from a Miniature Tissue

Scientists are always trying to model specific aspects of human biology. Since experimentation in humans is limited (clinical trials are a notable exception), scientists must find another way to learn about important biological functions, like how a cell divides, how our genes work and why they stop working normally and give rise to diseases like cancer. Only by understanding how normal processes break down and cause disease, can treatments for the disease be identified.

For decades, scientists have relied on model systems to study biological processes. For example, yeast, yes, similar to the one you bake with, and fruit flies, similar to the ones that swarm your overly-ripe bananas, have been instrumental in the identification and study of specific genes and their functions. Mice are currently the standard small animal model for in vivo, or in living systems, experiments. Although yeast, flies and mice are valuable models to learn about human biology, they are just that - models - and all model system have their strengths and weaknesses. One obvious weakness of the above models is that they are not human.

Organoids, or miniature organs, are a relatively new model system that has emerged from stem cell research and are making a big impact. These laboratory-grown, three-dimensional, mini-organs are microscopically small and are started from stem cells. Within a specialized growth environment, the stem cells, either adult or embryonic, depending on the tissue needed, are stimulated to grow and specialize into specific types of organoids. Although they are not exact replicas of the adult organ, they do replicate many aspects and thus give us a model of human development that we would not otherwise have. To date, organoids have been created to form a number of tissues including kidney, lung, gut, liver and brain.

Organoid technology has been around for several years, but as the methods to grow them become more sophisticated, their potential applications expand. Just this week, researchers from Yale University used organoids to model the brain development of individuals with severe autism spectrum disorder (ASD), a feat not possible in other model systems. Why? Most causes of ASD are unknown and thought to have multiple factors which makes it difficult, if not impossible, to model in any non-human system.

The Yale scientists took the approach of using cells from the affected families, which already contained the underlying defect, to model human brain development. By creating induced pluripotent stem (iPS) cells from the affected families, they could direct them to form brain organoids and then assess any differences between the organoids that developed from people with ASD compared to those from healthy people.

Interestingly, the development of the ASD brain organoids had similarities to what’s been observed in post-mortem analyses of human ASD brains. Notably, the ASD organoids had an over production of neurons, the cells that serve as the communication lines within the brain and body, and their connections were irregular. Additionally, in the ASD brain organoids the balance of neuron types was abnormal. This new discovery opens up the use of these organoids to further understand the development of ASD and potential treatments. Although we cannot predict if and when that will happen, this discovery puts us another step closer.

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