You may have seen videos of stem cell-derived cardiomyoctes beating in a dish, but did you know that a variety of human organs, like liver, kidney, and brain, can be partially recreated in vitro? Advances in human pluripotent stem cells (PSC) technology over the last 15 years has led to the development of several tissue model systems to improve our understanding of functional, developmental, and pathophysiological processes.

Human organoids are PSC-derived 3D cell cultures that self-organize into semi-functional surrogates of organs. These systems are more representative of in-vivo human biology than other cell-based models because they are composed of heterogeneous cell types and mimic the spatial organization patterns of authentic tissue. Importantly, organoids offer insights into the physiology of organs that are not safe or ethical to study by other means. They also bypass some of the drawbacks of using animal models to study human disease.

Dr. Alysson Muotri, a professor in the Department of Cellular and Molecular medicine at the University of California, San Diego, presented his research on human brain organoid technology and its applications to biomedical science in yesterday’s plenary session. Muotri reported that the primary application of brain organoids is to model neurological conditions, including autism spectrum disorder and some infectious diseases. For example, brain organoids were used to screen novel antiviral medications during the 2015 Zika virus outbreak and to model the neurotropic effects of SARS-CoV2 more recently. Importantly, these systems also provide insight into organogenesis, neurotoxicology, and are helping researchers assess the effects of space travel on brain physiology.

”I was always interested in the human brain,” Muotri said “However, most neuroscience labs work on animal models, especially the mouse.”

During graduate school, Muotri began to question how representative animal models were for human conditions and to ponder questions such as how the human cortex has such a fantastic computational ability. In his view, scientists could not effectively study these questions until 2008, when Yoshili Sasai from Japan developed the first organoids. Since that time, a variety of new models have been introduced and the bioengineering techniques used to create them have become more reliable and robust.

The inaccessibility and delicate nature of the brain are major barriers to studying human nervous system organogenesis, Muotri explained. Consequently, investigations of the anatomy and electrophysiology of the early brain have lagged behind discoveries for other organ systems. Muotri’s efforts are helping to close the gap. Although these miniaturized models are far from perfect replicas, they recapitulate the human brain in aspects of both form and function.

For example, an article from the New York Times featuring Muotri describes the similarities of brain organoid gyrification to the folds in our cortex. Researchers have detected rudimentary brain waves from these systems. This finding confirms that brain organoids are more representative of in-vivo biology than other cell-based systems, but also raises ethical concerns about the possibility of self-awareness.

Muotri believes that with continued innovation in neuroscience, the potential for human brain organoids to gain consciousness is far from science fiction. Anticipating this possibility, and the ethical controverses it may cause, ethicists and philosophers are now engaged in the evolution of human brain organoid technology. This moral guidance is critical for organoids to continue to advance as biomedical research tools while maintaining the interests of society at the forefront.