Researchers at HTPC partner organization CAAT create stem-cell derived mini-brains

CAAT's stem cell-derived "mini-brain"/image by Thomas Hartung (used with permission)

CAAT’s stem cell-derived “mini-brain”/image by Thomas Hartung (used with permission)

Researchers at Johns Hopkins’ Center for Alternatives to Animal Testing (CAAT) have developed a process to create “mini-brains” derived from stem cells reprogrammed from human skin cells. The resulting structures exhibit a number of cell types and cell functions of the human brain, and can be produced economically and in sufficient numbers to be especially useful for screening chemicals and drug candidates. The mini-brains will also be used to study Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and autism.

From CAAT’s press release:

“[Principal investigator] Hartung and his colleagues created the brains using what are known as induced pluripotent stem cells (iPSCs). These are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state and then are stimulated to grow into brain cells. Cells from the skin of several healthy adults were used to create the mini-brains, but Hartung says that cells from people with certain genetic traits or certain diseases can be used to create brains to study various types of pharmaceuticals. He says the brains can be used to study Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and even autism. Projects to study viral infections, trauma and stroke have been started.

Hartung’s mini-brains are very small—at 350 micrometers in diameter, or about the size of the eye of a housefly, they are just visible to the human eye—and hundreds to thousands of exact copies can be produced in each batch. One hundred of them can grow easily in the same petri dish in the lab. After cultivating the mini-brains for about two months, the brains developed four types of neurons and two types of support cells: astrocytes and oligodendrocytes, the latter of which go on to create myelin, which insulates the neuron’s axons and allows them to communicate faster.

The researchers could watch the myelin developing and could see it begin to sheath the axons. The brains even showed spontaneous electrophysiological activity, which could be recorded with electrodes, similar to an electroencephalogram, also known as EEG. To test them, the researchers placed a mini-brain on an array of electrodes and listened to the spontaneous electrical communication of the neurons as test drugs were added.

“We don’t have the first brain model nor are we claiming to have the best one,” says Hartung, who also directs the School’s Center for Alternatives to Animal Testing.

“But this is the most standardized one. And when testing drugs, it is imperative that the cells being studied are as similar as possible to ensure the most comparable and accurate results.”

Hartung elaborated on this point to Gizmodo: “There are a handful of such models described over the last two years,” he said. “They show more fancy brain structures, but each and every one looks different, often with cells in the middle dying because of lack of oxygen as they have no blood vessels. We produce hundreds of identical mini-brains, every week. This is critical for testing and comparing substances. They have exactly the same size below a critical diameter.”

Learn more in the video embedded here.

alternative toxicity testing brain organoids CAAT HTPC members in the news stem cells

The Year of the Brain (Organoid)

Cultivated neural tissue (photo credit: Michael Schwartz, University of Wisconsin-Madison)

Cultivated neural tissue (photo credit: Michael Schwartz, University of Wisconsin-Madison)

What sounded like science fiction just a couple of decades ago is a rapidly advancing reality today: in 2015, a number of research teams developed and refined stem cell-derived “brain organoids” that are already being used to model neurological diseases and test potential drug treatments.

Miniaturized human brain organoid grown from re-programmed adult skin cells (photo courtesy of Ohio State University)

Miniaturized human brain organoid grown from re-programmed adult skin cells (photo courtesy of Ohio State University)

We blogged about some of these studies in August 2015, and NIH Director Dr. Francis Collins featured brain organoids in a blog column in September. The Wall Street Journal’s science columnist, Shirley Wang, has an informative round-up of stem cell-based neurological disease models in her recent column.

In its year-end “breakthrough” round-up, MIT’s Technology Review magazine names brain organoids as one of the top technology breakthroughs of 2015. As the article explains, “What makes cerebral organoids particularly useful is that their growth mirrors aspects of human brain development. The cells divide, take on the characteristics of, say, the cerebellum, cluster together in layers, and start to look like the discrete three-dimensional structures of a brain. If something goes wrong along the way—which is observable as the organoids grow—scientists can look for potential causes, mechanisms, and even drug treatments.”

In addition to modeling diseases and testing potential treatments, these brain organoids can also be used to more efficiently and affordably assess other chemicals – such as those in pesticides or industrial agents – for neurotoxicity in humans.

3D cell & tissue culture brain organoids stem cells