Modeled Brain Performance: The Development of Mini Brain Organoids

By Nishi Jain ’21

The development of the mini brain organoids catalyzed the development of a potential cure to the Zika virus. (Source: Wikimedia Commons)

At the University of California Los Angeles, researched have further enhanced a method of studying complex neurological disorders—the creation of simplified human brain tissue derived from stem cells, or “mini brain organoids.”

These mini brain organoids, due to their ability to accurately mimic the development and growth of the brain, have the ability to lead scientists to more accurate experimentation results when looking at various neurological disorders that are associated with the development and growth of the brain.

Led by UCLA’s Ethel Scheibel Professor of Neurobiology Ben Novitch, the development of these mini brain organoids has opened new doors to research on the brain based on its ability to provide accurate research relative to the humans. “Mini brain organoids provide us with opportunities to examine features of the human brain that are not present in other models,” Novitch stated in a recent study published in the journal Cell Reports. “We anticipate that their similarity to the real human brain will enable us to test how various drugs impact abnormal or diseased brain tissue in far greater detail.”

Prior to the development of these mini brain organoids, human pluripotent stem cells were used to earlier versions of mini brain organoids. However, this tissue was often rendered unusable by the differing structures and cellular composition from those of the human brain, yielding results from experimentation that would conflict with the actual development of the neurological disorder on the human brain.

In order to make the brain tissue more specialized and work better in relation to the human brain, Novitch and his team at UCLA utilized a few techniques that seemed to eventually yield mini brain organoids that had a better structure and more uniform shape, as well as a longer life. They utilized a concrete number of stem cells and grew them in petri dishes which they placed in a modified chemical environment after adding a growth factor called LIF, which had the effect of stimulating cell-signaling pathways essential for neural growth and development. Beyond then just getting more uniform structure and longer life, the newly developed mini-brain organoids had an anatomy that resembled the cortex of the human brain well, different types of neurons (similar to that of the brain), and additionally had electrical function that mimicked that of the brain.

Research with these newly developed “mini brains” has already begun with the Zika virus, with Novitch and his team looking at the effects that the virus has on the development of fetal brain tissue. The research focalizes on the identification of drugs that could serve as preventative measures for potentially affected infants. The mini brain organoids, in their mimicry of the human brain, have provided scientists at UCLA with key information on how the virus can destroy neural stem cells—the Zika virus binds to receptors on the outer surface of neurons and then destroys them, thus leading to irreversible brain damage in infants.

The discovery of the interaction between the Zika virus and the neural stem cells in the mini brain organoids have led to the development of a few different drug therapies, a few of which are able to block entry into the brain tissue or simply prevent interaction between the receptors and the virus.

With continuing research on this subject, Novitch and his team hope to continue to work towards creating drug therapies using their modeled performance on the mini brain organoids to guide this development.

Source: Momoko Watanabe. Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection. Cell Reports, 2017 DOI: 10.1016/j.celrep.2017.09.047