A team of European scientists has grown parts of a human brain in tissue culture from stem cells. Their work could help scientists understand the origins of schizophrenia or autism and lead to drugs to treat them, said Juergen Knoblich, deputy scientific director at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences and one of the paper’s co-authors.
The advance could also eliminate the need for conducting experiments on animals, whose brains are not a perfect model for humans.
To grow the brain structures, called organoids, the scientists used stem cells, which can develop into any other kind of cell in the body. They put the stem cells into a special solution designed to promote the growth of neural cells. Bits of gel interspersed throughout the solution gave the cells a three-dimensional structure to grow upon. In eight to 10 days, the stem cells turned into brain cells. After 20 days to a month, the cells matured into a size between three and four millimeters, representing specific brain regions such as the cortex and the hindbrain.
Growing brain tissue this way marks a major advancement because the lab-grown brain cells self-organized and took on growth patterns seen in a developing, fetal brain.
Currently, the organoids are limited on how big they can get because they do not have a circulatory system to move around nutrients.
Knoblich’s team didn’t stop at growing the brain organoids, though. They went a step further and used the developing tissue to study microcephaly, a condition in which the brain stops growing. Microcephalic patients are born with smaller brains and impaired cognitive development. Studying microcephaly in mice doesn’t help because human and mouse brains are too different.
For this part of the study, the researchers used stem cells from a microcephalic patient and grew neurons in a culture. They found that normal brains have progenitor stem cells that make neurons and can do so repeatedly. In microcephalic brains, the progenitor cells differentiate into neurons earlier, said Madeline A. Lancaster, the study’s lead author. The brain doesn’t make as many neurons and a child is born with a much smaller brain volume.
Yoshiki Sasai, a stem-cell biologist at the Riken Center for Developmental Biology in Kobe, Japan, garnered headlines last year by growing the precursors to a human eye.
“The most important advancement is that they combined this self-organization culture with disease-specific cells to model a genetic disease of human brain malformation,” he said.
“Everything we have done with other organs starts with this stage,” said Dr. Anthony Atala, the director of the Wake Forest Institute for Regenerative Medicine, who has done years of research on using 3D printers to build organs. Atala was not involved in this study, but he noted that before he could build organs, he needed to grow the pieces in order to get the cells to differentiate in just the right way. So though it’s unlikely anyone will print brains the way he did a kidney, this kind of experiment is where organ regeneration starts.
Knoblich said the next step is studying other brain disorders, but it will take some time to grow enough brain tissue. One factor is maximum size and how far the brain can develop in the culture. Brain cells develop in layers, and there are several by the time a baby is born. The cortical cells Knoblich’s team grew only had one such layer. Another factor is getting blood vessels inside the tissue. That problem could be solved some time in the future, though he said he couldn’t predict when.
It is tempting to think one day there will be whole brains in vats, but that isn’t likely to happen.
“Aside from the severe ethical problem, I do not think this will be possible,” Knoblich said. To form actual functioning neural circuits, a brain needs sensory input. “Without any sensory input, the proper organization may not happen.”