Anasthasia Shilov

Amid a great deal of buzz in the neuroscience world surrounding cell revival in dead pig brains at Yale, a new brain study from the School of Medicine focusing on the development of human brain organoids has not gone unnoticed.

For the first time, researchers have developed novel human brain organoids that contain blood vessels, according to a study published in the prestigious scientific journal Nature Methods on Oct. 7. The organoids — millimeters in size — are 3D structural models of the developing human brain made from stem cells. In the past, these organoids tended to live for only a few months due to poor oxygen and nutrient exchange within the structure. This short functional period limited scientists’ ability to conduct in-depth studies of brain development using the organoids. However, by inducing the growth of blood vessels, the researchers have enabled their organoids to live for up to a year.

“Inside organoids containing these vascular-like structures, cell death was dramatically reduced,” said In-Hyun Park, senior author and School of Medicine genetics professor.

Allowing the neurons to mature over a longer period of time makes a big difference in terms of their health and functionality, explained one of the first authors, Bilal Cakir, a postdoctoral associate at the School of Medicine.

According to Cakir, scientists currently use postmortem adult brains for research. However, many neurological conditions such as psychiatric disorders are thought to arise from improper wiring that develops early in the brain’s maturation process. The new brain organoids present the unique opportunity to visualize the brain’s networks and study its development in real time.

Furthermore, having blood vessels makes the organoid a much more accurate model of a real human brain.

“First, you improve the properties of the brain organoid itself by providing a better environment for the neurons to grow. [Additionally], you create a system to study the blood-brain barrier,” said co-first author Yangfei Xiang, an associate research scientist at the School of Medicine.

Modeling the blood-brain barrier is crucial for understanding brain development, mechanisms of neurodegenerative disease and drug uptake in the brain, Xiang explained. The struggle to pass through this structure is one of the main reasons why treating neurological diseases is so difficult.

“Of course, this is not the whole picture,” said Xiang. “We need to use other model systems to fully understand the story. You still need to use animal models or postmortem human brain tissue.”

One of the main concerns in the April pig brain study was that reviving the tissue would also bring back the animal’s memories and feelings. But, for now, research is far from creating consciousness in the lab.

“In terms of cognition or emotion, I don’t think any kind of brain organoid — even our vascularized organoids — have that yet,” Park said.

Moving forward, Xiang said he would be interested in using the organoid to test treatments for neurological diseases, such as Alzheimer’s disease. Since the vascularized organoid mimics the blood-brain barrier, the model could be used to more accurately test the ability of drugs to pass through this structure to their target locations in the brain.

Xiang is also interested in using gene editing on the cells of the brain organoid to study neurological disorders, he said. Still, Cakir added that immune cells are missing in the brain organoids, making it difficult to study the pathology of some neurological diseases. He is currently working to implement immune cells in a brain organoid model.

According to the United Nations, about 1 billion people worldwide suffer from neurological diseases.

 

Ashley Qin | ashley.qin@yale.edu

Correction, Oct. 23: A previous version of article incorrectly stated that Park’s research was published in Nature. In fact, it was published in a science journal called Nature Methods.