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Brain cell culture goes 3D

A cross-section of a cerebral organoid (Image copyright: IMBA/ Madeline A. Lancaster)

A cross-section of a cerebral organoid (Image copyright: IMBA/ Madeline A. Lancaster)

Some brain diseases, such as microcephaly, can’t be studied in animals. Now researchers have developed a technique to grow early-stage brain tissue in the lab, opening up possibilities from studying diseases to testing drugs. MRC Senior Press Officer Hannah Isom reports.

As a science press officer, I’m in the privileged position of getting my mitts on some of the most exciting research papers before they are seen by the world’s media, and even by other scientists in the field. Sometimes I worry I’m so awash with impressive discoveries that I’ll become complacent. And then every once in a while a paper lands in my inbox that is so exciting — even to a non-scientist like me — that I know I don’t need to be concerned.

This week in Nature scientists led by the Institute of Molecular Biotechnology in Austria, in collaboration with the MRC Human Genetics Unit at the University of Edinburgh, have revealed that they have used stem cells to grow a three-dimensional structure in the lab that resembles primitive human brain tissue.

The process relies on the stem cells’ innate ability to arrange themselves into complex 3D structures. Well, that and gel-based scaffolding and a spinning bioreactor that circulates oxygen and nutrients to feed the growing tissue.

At just two months old and only four millimetres long (about the size of a grain of rice), a fully-fledged ‘cerebral organoid’ may not look like much, yet it shares many of the characteristics of the human brain in the earliest stages of development.

Aside from the wow factor of growing brain-like tissue, the organoids can be used by scientists to study human brain development and brain diseases in a way that has never before been possible.

The bioreactor, with (left) organoids suspended in fluid (Image copyright: IMBA/Magdalena Renner)

The bioreactor, with (left) organoids suspended in fluid (Image copyright: IMBA/Magdalena Renner)

Most of what we know about how the human brain develops during pregnancy has come from studies using animals — usually mice. Scientists can also use mice to study a wide range of human diseases, often by changing the genetic code of the animal so that it displays certain traits or symptoms.

But while mice have been invaluable for telling us what goes wrong in many brain diseases, there are some that scientists have not been able to recreate fully in animals. Microcephaly — a rare genetic condition that results in a small brain and head — is one such example.

Once the researchers had shown that the organoid technique worked, they set about producing organoids that would develop in a way similar to the brains of people with microcephaly. They used skin cells donated by a microcephaly patient to generate stem cells, and then organoids. They learnt that problems with neural stem cell division in the early stages of development underlie the condition.

They hope the organoid system will allow them to study abnormal brain development, as well as increasing our understanding of how the normal brain grows in the womb. It also opens up the possibility of using cerebral organoids to evaluate the safety and effectiveness of experimental drugs, before they are tested on animals or humans.

Does this mean that we’re a step closer to growing a fully formed human brain in a dish? Well, not really. And nor would we want to. While this advance raises the possibility that one day we might be capable of growing a more complex structure, there’s an important difference between what’s possible and what’s desirable.

Making the decision to create a full-sized human brain with thoughts and feelings is one that would never be taken lightly by the scientific community, and is perhaps one best left to science fiction.

Hannah Isom

Reference: Nature (2013) doi:10.1038/nature12517


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