Growing human brain cells in the lab

October 10, 2017, Gladstone Institutes
Credit: Gladstone Institutes

Li Gan, PhD, wants to find treatments to help patients with Alzheimer's disease. Like most researchers, she's hit a few major roadblocks.

When researchers like Gan find potential new drugs, they must be tested on human to confirm they can benefit patients. Historically, these tests have been conducted in , which often don't match the biology of human cells.

"The problem is that brain cells from actual people can't survive in a dish, so we need to engineer in the lab," explained Gan, senior investigator at the Gladstone Institutes. "But, that's not as simple as it may sound."

Many scientists use induced (iPSCs) to address this issue. IPSCs are made by reprogramming to become stem cells, which can then be transformed into any type of cell in the body. Gan uses iPSCs to produce brain cells, such as neurons or , because they are relevant to neurodegenerative disease.

Human brain cells derived from iPSCs offer great potential for drug screening. Yet, the process for producing them can be complicated, expensive, and highly variable. Many of the current methods produce cells that are heterogeneous, or different from one another, and this can lead to inconsistent results in drug screening. In addition, producing a large number of cells is very costly, so it's difficult to scale up for big experiments.

To overcome these constraints, Michael Ward, MD, PhD, had an idea.

A New Technique Is Born

"I came across a new method to produce iPSCs that was developed at Stanford," said Ward, a former postdoctoral scholar in Gan's lab who is now an investigator at the National Institutes of Health. "I thought that if we could find a way to simplify and better control that approach, we might be able to improve the way we engineer human brain cells in the lab."

Ward and his colleague Chao Wang, PhD, discovered a way to manipulate the genetic makeup of cells to produce thousands of neurons from a single iPSC. This meant that every engineered brain cell was now identical.

"I was truly motivated by our initial results," said Gan, who is also a professor of neurology at UC San Francisco. "I had observed too much variability using the traditional method, which made reproducing experiments quite problematic. So, the ability to produce homogeneous human brain cells was very exciting."

The team further improved the technique to create a simplified, . This allows scientists to precisely control how many brain cells they produce and makes it easier to replicate their results from one experiment to the next.

Their technique also greatly accelerates the process. While it would normally take several months to produce brain cells, Gan and her team can now engineer large quantities of them within 1 or 2 weeks, and have functionally active neurons within 1 month. 

The researchers realized this new approach had tremendous potential to screen drugs and to study disease mechanisms. To prove it, they tested it on their own research.

They applied their technique to produce human neurons by using iPSCs. Then, they developed a drug discovery platform and screened 1,280 compounds. Their goal is to identify the compounds that could lower levels of the protein tau in the brain, which is considered one of the most promising approaches in Alzheimer's research and could potentially lead to new drugs to treat the disease.

"We showed that we can engineer large quantities of human brain cells that are all the same, while also significantly reducing the costs," said Wang, Gladstone postdoctoral scholar. "This means our technology can easily be scaled up and can essentially be used to screen millions of compounds."

A Powerful Tool for the Entire Scientific Community

"We have developed a cost-effective technology to produce large quantities of human brain cells in two simple steps," summarized Gan. "By surmounting major challenges in human neuron-based drug discovery, we believe this technique will be adopted widely in both basic science and industry."

Word of this useful new technology has already spread, and people from different scientific sectors have come knocking on Gan's door to learn about it. Her team has shared the new method with scores of academic colleagues, some of whom had no experience with cell culture. So far, they all successfully repeated the two-step process to produce their own cells and facilitate scientific discoveries.

Details of this new technique were also published on October 10, 2017, in the scientific journal Stem Cell Reports.

With some of the roadblocks out of the way, Gan hopes more discoveries will soon help the millions who suffer from Alzheimer's disease.

Explore further: New stem cell method produces millions of human brain and muscle cells in days

More information: Chao Wang et al. Scalable Production of iPSC-Derived Human Neurons to Identify Tau-Lowering Compounds by High-Content Screening, Stem Cell Reports (2017). DOI: 10.1016/j.stemcr.2017.08.019

Related Stories

New stem cell method produces millions of human brain and muscle cells in days

March 23, 2017
Wellcome Trust Sanger Institute scientists and their collaborators at the University of Cambridge have created a new technique that simplifies the production of human brain and muscle cells - allowing millions of functional ...

A star is born: Lesser-known brain cell takes center stage

June 6, 2017
Neurons have long enjoyed the spotlight in neuroscience—and for good reason: they are incredibly important cellular actors. But, increasingly, star-shaped support cells called astrocytes are being seen as more than bit ...

Large-scale production of living brain cells enables entirely new research

June 26, 2017
Important pieces of the puzzle to understand what drives diseases such as Alzheimer's and Parkinson's are still missing today. One crucial obstacle for researchers is that it is impossible to examine a living brain cell in ...

Micro heart muscle created from stem cells

April 20, 2016
Scientists at the Gladstone Institutes have invented a new way to create three-dimensional human heart tissue from stem cells. The tissue can be used to model disease and test drugs, and it opens the door for a precision ...

Recommended for you

Animal study connects fear behavior, rhythmic breathing, brain smell center

April 20, 2018
"Take a deep breath" is the mantra of every anxiety-reducing advice list ever written. And for good reason. There's increasing physiological evidence connecting breathing patterns with the brain regions that control mood ...

Researchers identify blood biomarkers that may help diagnose, confirm concussions

April 20, 2018
Researchers from the University of California, Irvine, Georgetown University and the University of Rochester have found that specific small molecules in blood plasma may be useful in determining whether someone has sustained ...

Mechanism behind neuron death in motor neurone disease and frontotemporal dementia discovered

April 20, 2018
Scientists have identified the molecular mechanism that leads to the death of neurons in amyotrophic lateral sclerosis (also known as ALS or motor neurone disease) and a common form of frontotemporal dementia.

When there's an audience, people's performance improves

April 20, 2018
Often, people think performing in front of others will make them mess up, but a new study led by a Johns Hopkins University neuroscientist found the opposite: being watched makes people do better.

Signaling between neuron types found to instigate morphological changes during early neocortex development

April 20, 2018
A team of researchers from several institutions in Japan has found that developing neocortex neurons in mammals undergo a morphological transition from a multipolar shape to a bipolar shape due at least partially to signaling ...

MRI technique detects spinal cord changes in MS patients

April 20, 2018
A Vanderbilt University Medical Center-led research team has shown that magnetic resonance imaging (MRI) can detect changes in resting-state spinal cord function in patients with multiple sclerosis (MS).

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.