The tiny ‘brains’ mimic early brain development in a human embryo.

It is nowhere near a ‘brain in a dish’ of science fiction lore. However, scientists have successfully cultured stem cells to produce a pea-sized blob that mimics early brain development in a human embryo.

In a paper that has just been published online by Nature, Juergen Knoblich of the Institute of Molecular Biotechnology of the Austrian Academy of Science in Vienna and his colleagues reported growing tiny “cerebral organoids” in the laboratory that had many key features of the brain in a nine-week-old human embryo.

Their culture system was able to produce such miniature brains using human embryonic stem cells as well as mature cells that had been reprogrammed.

“Our system is very useful for us as developmental biologists because it allows us to study the human-specific features of brain development,” explained Dr. Knoblich during a press briefing. “We can analyse the function of individual genes in a human setting and that gives us much more information about what these genes may be doing.”

The cells of the cultured version grew around a fluid-filled cavity that was reminiscent of the ventricles in the human brain. The tiny organoids developed two of the six layers found in a brain’s outer portion, the cerebral cortex, along with cells typically associated with those layers. It also had some of the major regions that an embryonic human brain possesses and which later become more complex.

The organoids had a type of neural stem cell that are found abundantly in the human embryonic brain but are hardly seen in lower mammals like rodents, Madeline Lancaster, a postdoctoral researcher in Dr. Knoblich's laboratory and the paper’s first author, told journalists.

However, the cultured organoids have limitations. They do not yet display all the brain regions organised in the fashion that would be found in a developing embryo. Moreover, without blood vessels taking oxygen and nutrients to cells deep inside, the organoids do not grow and develop beyond about four millimetres in size.

The scientists were able to use their culture system to model a disease that affected early brain development. Microcephaly is a devastating genetic disorder that leads to greatly reduced brain size and associated mental disabilities in afflicted individuals.

Attempts to study the disease in mice had failed to recapitulate what was seen in humans.

The scientists were able to generate tiny brains with reprogrammed skin cells taken from a person with the disorder.

The organoids from this individual were much smaller than those created from a healthy person, said Dr. Lancaster. In this form of microcephaly, neural stem cells, which ought to be expanding in number, had started making neurons too soon. As a result, the stem cell population got depleted and, in the end, fewer neurons were made, resulting in a smaller brain.

“Ultimately we would like to move to more common disorders like schizophrenia or autism,” which too produced defects in early brain development, remarked Dr. Knoblich.

Culturing these tiny organoids provided a “fabulous model system” for studying uniquely human aspects of brain development both in healthy and disease states, remarked Shyamala Mani of the Indian Institute of Science in Bangalore who works on embryonic brain development.

Responding to a question, Dr. Knoblich said that he was pessimistic about using the method to grow tissue that would replace damaged or diseased parts of the brain. However, their cultured bits of brain could be very useful in testing new drugs, he suggested.

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