3D ‘mini-brains’ help understand rare developmental disorders.

06-04-2017
HT

Scientists have grown 3D ‘mini-brains’ from stem cells and used them to better understand how a rare congenital brain defect develops.

A new method could push research into developmental brain disorders an important step forward, researchers said. Scientists at the University of Bonn in Germany converted skin cells from patients into induced pluripotent stem cells.

From these ‘jack-of-all-trades’ cells, they generated brain organoids – small 3D tissues which resemble the structure and organisation of the developing human brain.

Investigations into human brain development using human cells in the culture dish have so far been very limited: the cells in the dish grow flat, so they do not display any three-dimensional structure.

Model organisms are available as an alternative, such as mice. The human brain has, however, a much more complex structure. Developmental disorders of the human brain can thus only be resembled to a limited degree in the animal model.

Scientists at the University of Bonn applied a recent development in stem cell research to tackle this limitation: they grew 3D organoids in the cell culture dish, the structure of which is incredibly similar to that of the human brain.

These “mini brains” offer insight into the processes with which individual nerve cells organise themselves into our highly complex tissues. In their work, the scientists investigated the Miller-Dieker syndrome – a hereditary disorder is attributed to a chromosome defect. As a consequence, patients present malformations of important parts of their brain.

“In patients, the surface of the brain is hardly grooved but instead more or less smooth,” said Vira Iefremova, from University of Bonn. The researchers produced induced pluripotent stem cells from skin cells of Miller-Dieker patients, from which they then grew brain organoids.

In organoids, the brain cells organise themselves very similar to the process in the brain of an embryo: the stem cells divide; a proportion of the daughter cells develops into nerve cells; these move to wherever they are needed.

These processes resemble a complicated orchestral piece in which the genetic material waves the baton. In Miller-Dieker patients, this process is fundamentally disrupted.

“We were able to show that the stem cells divide differently in these patients,” said Philipp Koch, associate professor from the University of Bonn. “In healthy people, the stem cells initially extensively multiply and form organised, densely packed layers. Only a small proportion of them becomes differentiated and develops into nerve cells,” said Koch, who led the study.

Certain proteins are responsible for the dense and even packing of the stem cells. The formation of these molecules is disrupted in Miller-Dieker patients.

The stem cells are thus not so tightly packed and, at the same time, do not have such a regular arrangement. This poor organisation leads, among other things, to the stem cells becoming differentiated at an earlier stage.

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