Brains grown in the lab could stop damaging brain parts
Researchers are growing “mini-brains” — smaller than the period at the end of this sentence — that may contain enough human brain cells to be useful in studying drug addiction and other neurological diseases.
The mini-brains, grown in a laboratory dish, could one day reduce the need for the use of laboratory animals to conduct this type of research or to test therapeutic drugs.
Labs from around the world have been racing to grow these and other organoids — microscopic, yet primitively functional versions of livers, kidneys, hearts, and brains grown from real human cells. The version of the mini-brain from Johns Hopkins represents an advance over others reported in the last three years, in that it is quickly reproducible and contains many types of brain cells that interact with each other, just like a real brain.
The mini-brains’ three-dimensional structure and ability to carry neurotransmitters — chemical messengers such as dopamine that enable communication between neurons — provide a simple but relatively realistic platform to study what goes wrong in the brain in, say, drug addiction and how the problem can be remedied.
The mini-brain model is well-suited for studying brain addiction, in that scientists can study how drugs can destroy glia cells. Such destruction leads to the death of neurons and poorer transmission of neural impulses.
Although the mini-brain cannot yet replace animal models in the study of neurological diseases. But the concept, which until recently seemed years from maturity, may be realized by British scientists.
The tiny organs are being grown in a British laboratory, where the scientists believe they will one day be able to use them to grow new brain tissue.
The process involves transforming skin cells into neurons, which are then 3D-printed into structures that resemble the brain.
The treatment, if successful, would not be able to reverse memory loss that has already occurred but it could stop further deterioration.
The brain in a petri dish
This is not the first time that stem cells have been used to grow artificial brain tissue. In April, researchers at Stanford University grew two forebrain circuits, measuring only a sixteenth of an inch across, using only human skin cells.
Human skin cells are transformed into pluripotent stem cells, capable of becoming any part of the body, using four genes in a petri dish.
These help them ‘unlearn’ that they are skin cells and return to the state of a newborn baby’s cells.
The ‘culture’, or nutrient-rich broth they are grown in, is then altered to determine which type of cell they will become — in this case brain cells, or neurons.
This resulted in a 60-day old forebrain like a baby’s in the womb, although more scrambled in its connections.
It includes the cerebral cortex, the most highly evolved ‘thinking’ and decision-making part of the brain.
Scientists hope to use the mini-brains to watch in real time the triggers for epilepsy, when brain cells become hyperactive, and autism, where they are thought to form bad connections.
Scientists now reject claims of lab-grown mini human brain
What this all about?
Mini-brains 3 to 4 millimeters across have been grown in the lab before, but if a larger brain had been created — and the press release publicizing the claim said it was the size of a pencil eraser — that would be a major breakthrough. New Scientist investigated the claims.
Anand says he has grown a brain — complete with a cortex, midbrain, d brainstem — in a dish, comparable in maturity to that of a fetus aged 5 weeks. Anand and his colleague Susan McKay started with human skin cells, which they turned into induced pluripotent stem cells (iPSCs) using a tried-and-tested method. By applying an undisclosed technique, one that a patent has been applied for, the pair says they were able to encourage these stem cells to form a brain.
“We are replicating normal development,” says Anand. He says they hope to be able to create miniature models of brains experiencing a range of diseases, such as Parkinson’s and Alzheimer’s.
But not everyone is convinced, especially as Anand hasn’t published his results. Scientists we sent Anand’s poster presentation to said that although the team has indeed grown some kind of miniature collection of cells, or “organoids,” in a dish, the structure isn’t much like a fetal brain.
Jürgen Knoblich of the Institute of Molecular Biotechnology in Vienna, Austria, grew a similar brain-like structure in 2013, albeit without a midbrain. He says that Anand hasn’t presented enough evidence to show that his organoids really has all the typical parts of a brain.
The only way the team can be sure they have grown the equivalent of a fetal brain would be to genetically test individual cells from different regions of the organoids, and compare them to those of human fetus, says Christof Koch at the Allen Institute for Brain Science in Seattle. “There is no evidence that [Anand] has done this.”
Anand says he performed a genetic analysis of the brain-like structure as a whole, and that he found 99 per cent of the genes known to be expressed in the human brain. But he hasn’t analyzed the different parts of the brain on their own.
“The fact that a [cell] culture expresses most genes present in the brain says nothing about its appropriateness as a disease model,” says Knoblich. “Without using markers for different brain regions, the claim that he has achieved a 3D model of the brain is entirely unjustified.”
Under the radar
“I do not see any full development of major parts of the brain,” agrees Elena Cattaneo, who directs the Centre for Stem Cell Research at the University of Milan in Italy.
Anand says that he wasn’t able to test separate regions of the mini-brain. It was too small to slice up, he says. Cattaneo disagrees. “The structure is quite big,” she says, big enough to test individual slices.
Koch adds that there is no evidence that the cells are connected to the neurons in our brains. “They are a bunch of cells in a dish, like a soup,” he says.
Anand disputes this and says he has early results suggesting that electrical activity can spread through the organoids in the same way it would through a human brain.
Researchers are also ruled that none of Anand’s work on this project has been subject to peer review. Anand told New Scientist that while he does respect the peer review process, he is confident enough of his results to start publicizing them, with the aim of attracting potential collaborators.
“It would have helped Anand’s case if he had followed standard scientific procedures and published these findings instead of seeking to immediately monetize them,” says Koch.
Acknowledgments & References
The researchers, led by Dr. Thomas Hartung, director of the Johns Hopkins Center for Alternatives to Animal Testing. Image of contention by jessica hamzelou. A mini-brain, from the Johns Hopkins Lab. Credit: Johns Hopkins Bloomberg School of Public Health.