Brain Organoids Usher in New Research Era

By Kevin Ritchart

A new method of developing brain organoids from pluripotent stem cells could prove to be an important step forward in the study of human neurological disorders. Researchers from the University of Bonn in Germany published a study in a recent issue of Cell Reports that outlined a unique approach to examining a rare congenital brain defect.

The German team took skin cells from patients and converted them into pluripotent stem cells. From these stem cells, they grew three-dimensional brain organoids or “mini-brains” that mimic the structure of the human brain.

Overcoming Historical Barriers in Human Brain Research

The ability of scientists to perform meaningful research on the human brain using human cells has been limited to date. Typically, cells in culture grow in a flat, two-dimensional layer. Without a three-dimensional model, researchers cannot accurately determine cellular changes when outside stimuli are introduced.

While some testing is done on the brains of mice and other animals, there are problems with the reliability of the results of such research. The human brain is much more complex than an animal’s, so human developmental disorders can only be studied on a limited basis while using animal brain models.

Watching Cells Get Organized

The new brain organoids can show scientists how nerve cells organize themselves into highly complex brain tissues. “The method thus opens up completely new opportunities for investigating disorders in the architecture of the developing human brain,” said Dr. Julia Ladewig, who leads a working group on brain development.

Dr. Ladewig and her colleagues used brain organoids to study Miller-Dieker Syndrome, a hereditary disorder that’s believed to be caused by a chromosomal defect. Patients with this disease present with malformations in vital parts of the brain.

Surprised by Signs of Cell Disruption

Researchers used skin cells from Miller- Dieker patients to create brain organoids to observe how the cells would react. Instead of seeing the organization and multiplication patterns of healthy cells, these processes were disrupted in the cells from Miller-Dieker patients.

In healthy patients, specific proteins are responsible for the dense and even packing of cells. The cells from Miller- Dieker patients are much more loosely packed and less organized, which leads to cell differentiation at an earlier stage. This particular behavior was not evident in previous two-dimensional cell culture growth.

While no new treatments are available at this time, researchers are hopeful that more work in this area will result in breakthroughs to help patients with Miller-Dieker Syndrome and other neurological disorders.

“We are undertaking fundamental research here,” Dr. Ladewig said. “Nevertheless, our results show that organoids have what it takes to herald a new era in brain research. And if we better understand the development of our brain, new treatment options for disorders of the brain can presumably arise from this over the long term.”