This U of M scientist is growing mini-brains in a dish

Tim O'Brien's petri dish brain organoids will help shed light on Alzheimer's, Parkinson's, and other diseases.

Tim O'Brien's petri dish brain organoids will help shed light on Alzheimer's, Parkinson's, and other diseases. University of Minnesota/Tim O'Brien

 A University of Minnesota researcher is growing brains.

Professor Tim O’Brien has been working full-time at the U since 1985. For the last five years, his researched has involved turning induced pluripotent stem cells (commonly called IPS cells) into "brain organoids" – what can be best understood as mini-brains in a dish. He hopes his work can eventually be used to find better ways to treat nervous system disorders like Parkinson’s or Alzheimer’s disease.

“[IPS Cells] can be made from anybody, adults,” he said.

O’Brien first places the IPS cells into a hydrogel-filled material, and, after 10 to 14 days, they cultivate into visible brain tissues.

For O’Brien, this means he is able to develop the cells into the exact section of the brain that Parkinson’s affects, and then directly study how the disease works, and how drugs affect it. Organoids can take various forms, from brains to intestines.

“You can’t experiment with patients for a lot of things,” he said. “It provides the opportunity to make Alzheimer’s mini-brains … this is another application, this ‘disease in a dish.’”

O’Brien received a $50,000 National Science Foundation grant in December to fund training for him and his two-person staff to find commercial applications for his research. While O’Brien says human clinical applications are far off, using the research for improved drug screening is a realistic and relatively imminent goal.

Beyond the study of cells, drug trials are more precise with organoids as well. Drugs are generally tested on animals before human trials, and, when it comes to neurological disorders, this has proved to be both costly and unreliable.

“There is enormous differences between the human brain and the brain of a mouse,” says Dr. Arnold Kreigstein a professor at the University of California San Francisco who studies the nervous system using organoids. “The process of screening those drugs in human models instead of mice models is thought of as much more promising.”

Alzheimer's and Parkinson's are degenerative diseases, in Parkinson’s case it commonly known to start out with a tremble in the hand or leg. Over time, the disease can escalate into the patient struggling to walk, talk, and a variety of other debilitating symptoms. According to the Parkinson’s Foundation, about a million Americans have the disease.

Dr. Jerrold Vitek, head of the University of Minnesota’s Neurology Department, researches Parkinson’s and has advanced treatment options for it, including implanting wires that soothe tremors through electrical currents.

The disease begins when cells that make dopamine die, setting off a series of events resulting in miscommunication among cells. There’s a weird catch with Parkinson’s though – “It’s not the same in every patient,” Vitek says. “It’s kind of a common pathology, but there’s a lot of variation in this theme.”

Vitek says organoids is part of a set of tools that scientists are used to work on researching Parkinson’s. His work on brain circuits has used both human and animal models to investigate when these circuits malfunction. Combining various methods and disciplines, like organoid research and circuit research, is key to speeding up more meaningful research on the disease, says Vitek.

The process is called "localization," or when various scientists from different research and interest backgrounds collaborate. The ideas is to combine findings from brain imaging and brain organoids research for a better, collaborative solution.

“[Organoids are] pretty novel, unique stuff,” Vitek said. “I don’t think it going to be ‘the answer,’ [organoids] working by themselves in a vacuum.”

IPS cells were first developed in 2012 in Japan. They are sensible for researchers to use, and avoid the ethical controversy that has followed use of embryonic stem cells, which can develop into almost any kind of cells, opening a world of research and testing possibilities. To get those cells involves destroying a human embryo, which conservative critics view as destroying human life.

IPS cells, meanwhile, can come from any cell of the body -- meaning they're more readily available --and can be reprogrammed to act like embryonic stem cells, minus the controversy.

“With the advent of that [IPS cells,] one no longer had the challenge of the ethics surrounding the destruction of embryos,” Kriegstein said.

O’Brien says that while embryonic and IP stem cells are not identical, there’s negligible difference between their research usage.

For now, O’Brien is still wading through the initial stages of his research before it can be considered for any commercial applications. His lab team is working on stopping tumors from appearing when modifying cells, which has been successful so far, and in the months to come he’s set on writing grants for more funding, which are highly competitive.

O’Brien estimates that, at best, researchers have a 1-in-10 chance to receive a requested grant from the National Institutes of Health (NIH).

“Getting substantial funding is always difficult,” he says. “There’s no easy pathway to that.”