Dutch Scientists Grow Mini-brains in the Lab

It might sound like a deleted scene from a Tim Burton film, but scientists have grown 3D mini-organs from human fetal brain tissue. Not only that – these mini-organs can self-organize in a dish. These lab-grown “mini-brains,” as the scientists at the Princess Máxima Center and the Hubrecht Institute call them, blaze a new trail for future research.

It also presents a new perspective on the development and treatment of brain diseases and tumors. The Dutch researchers published the results of this groundbreaking study, subsidized by the Dutch Research Council, in the journal Cell.

A New Approach to Lab Research

Over the years, lab researchers have used a variety of techniques to replicate the way healthy tissue operates to study how diseases attack them, whether it’s cell lines, lab animals, and, more recently, 3D “mini-organs,” or organoids. They boast the same attributes as the real thing, which lets researchers study how organs work in a controlled setting.

However, the brain proved to be more difficult to replicate in the lab – until now.

The research team, led by Delilah Hendriks, MD, Hans Clevers, MD and PhD, and Benedetta Artegiani, MD, discovered that by taking small pieces of fetal brain tissue – as opposed to individual cells – provided the key component to growing these mini-brains.

Growing other organs in the lab typically requires the single-cell approach, but the brain demands something else.

The brain organoids these scientist cultivated were no larger than a grain of rice. But they possessed features that made them eerily similar to the human brain. According to their research:

1. The tissue’s 3D makeup was complex. It contained several different types of brain cells, including the so-called outer radial glia – a cell type found in humans and our evolutionary ancestors.
2. The organoids also produced proteins that make up the extracellular matrix – or “scaffolding” around the cells.
3. Finally, the organoids kept various characteristics of the specific region of the brain from which they were derived. They also responded to molecules directing their development.

“Brain organoids from fetal tissue are an invaluable new tool to study human brain development,” Dr. Benedetta Artegiani, research group leader at the Princess Máxima Center who co-led the research, explained. “We can now more easily study how the developing brain expands. And look at the role of different cell types and their environment. Our new, tissue-derived brain model allows us to gain a better understanding of how the developing brain regulates the identity of cells. It could also help understand how mistakes in that process can lead to neurodevelopmental diseases such as microcephaly. As well as other diseases that can stem from derailed development, including childhood brain cancer.”

Mini-brains Offer New Research Potential

Since the tissue-derived organoids expanded rapidly, the team realized the potential for modeling the development and growth of brain cancer.

By leveraging the gene editing tool CRISPR to introduce faults in the well-known cancer gene TP53 in a small number of cells in the organoids, the researchers discovered that “after three months, the cells with defective TP53 had completely overtaken the healthy cells in the organoid – meaning they had acquired a growth advantage, a typical feature of cancer cells.”

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