It’s a tiny little thing, no bigger than a pencil eraser and certainly not capable of thinking for itself, but it’s got all the major structures and 99 percent of the genes present in the brain of a five-week-old fetus.
In other words, scientists at Ohio State University say, it’s the most complete model of a human brain ever grown in a lab.
If approved for use in research, the tiny organoid unveiled at the Military Health System Research Symposium in Fort Lauderdale, Fla. on Tuesday could improve research into a whole host of brain-related illnesses, including autism, Parkinson’s and post-traumatic stress disorder.
Because the process hasn’t been published in an academic study, other scientists were hesitant to judge the quality of Rene Anand and Susan McKay’s work.
“When someone makes such an extraordinary claim as this, you have to be cautious until they are willing to reveal their data,” Zameel Cader, a consultant neurologist at the John Radcliffe Hospital, Oxford, told the Guardian.
But Anand is hopeful about the model’s prospects.
“It’s a scalable model that can be engineered to carry the genetic variants that give rise to all these diseases … and it gives us incredible access to things we never have done before,” lead researcher Anand told The Washington Post. “We can screen drugs, we can ask questions, we can follow the development at every stage.”
“And,” he noted, “we can do it all in a dish.”
Anand is a professor in Ohio State’s pharmacology department, and before he became interested in lab-grown brains he worked mostly on developing drugs related to autism and addiction.
But around four years ago he became frustrated with his efforts testing on rats and mice. Rodents are very useful early test subjects, but their brains are, frankly, not the same as a human’s. And the lab-grown brain models available at the time were mostly incomplete. You could test on individual brain components — the cortex, say, or the hippocampus — but you couldn’t see how a medication affected the organ as a cohesive unit.
If only there was a way to experiment on a complete human brain without experimenting on an actual human.
In 2012 a Japanese researcher Shinya Yamanaka shared the Nobel Prize for his work on stem cells, in which he “induced” ordinary skin cells from adults to revert back to their earliest embryonic state. Those “pluripotent” cells could then be grown into an array of other types of tissue: heart muscle, bone, nerve cells.
A year later, a group of Austrian and British scientists used Yamanaka’s technique to produce the part of an embryo that develops into a brain and spinal cord, called the neuroectoderm. They then altered the RNA of the tiny organoid — which resembled the brain of a fetus at nine-weeks — to model a rare neurological condition called microcephaly, and found that it was caused by early problems as ordinary cells develop into neurons.
It was one of the first times that a brain grown from pluripotent cells was able to replace the traditional test subjects of mice and computer models. Other organs have been modeled from the pluripotent state, but the brain is the “holy grail,” Anand said, because it is far and away the most complex.
Buoyed by previous advances, Anand sought to develop his own model, one that would contain even more of the structures necessary to build a complete human brain.
Due to a pending patent, Anand has not published the details of how he developed his brain model. But he’s already enthusiastic about the results of the process.
“The model has everything,” he said. “We have the midbrain, the area that gets affected in Parkinson’s. We have the spinal cord, the circuitry, the different cell types,” everything except a vascular system.
If the model is approved, researchers could take a skin cell from a patient with Parkinson’s, induce it to become pluripotent using Yamanaka’s technique, then grow the resulting stem cell into a brain based on Anand’s process. They could then study the organoid to find clues about the illness in the brain’s early development. The research will help bridge the gap between what we know about genetic predisposition to neurological problems and how they manifest in living people, Anand said.
He and his co-researcher, McKay, are already using the process to create models of Alzheimer’s, Parkinson’s and autism in a dish. It could also be used to study PTSD, he said (which is part of why he presented his research at a military symposium). If he and McKay are able to develop their model even further so that it includes a blood supply, they also hope to be able to study strokes.
They have also founded a Columbus, Ohio-based start-up, NeurXstem, to commercialize their model.
“It won’t replace mice and rats entirely,” Anand said, but I think it’s going to add value and become a pre-clinical model on which we can test a lot of things,” he said. “It lets you test all your ideas in the dish, so when you got to a patient you have a much better chance of getting it right.”
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