Researchers at the Houston Methodist Research Institute are making 3-D mini brains from human stem cells. They hope that such models can help with research on repairing the nervous system after injury or disease of the brain. The researchers have developed a way to reduce the time required to grow these brain models which will allow for faster testing of drugs and study of disease-causing mutations. For the first time when the researchers put the cells together, they dramatically changed their morphological complexity, size, and shape. They believe they look like cells you would see in the human brain.
Cells traditionally grown in lab cultures are put on a flat petri dish where they are often manipulated and thus their interactions are disturbed. The form, structure, and developmental growth of the brain’s cells are thus not able to be reproduced and the cells look very simplistic. In the human brain, these cells are complex and interact with each other and the environment. 3-D culture systems are being developed but studies with them require a lengthy period of time.
Growing 3-D mini brains takes months and years to develop. The researchers developed techniques to pre-mature the cells separately and then combine them. After several weeks the cells were able to form mature interactions with each other allowing for studies to be conducted must faster. The research focused on a star-shaped cell type called astrocytes, as they are a key factor in getting the brain’s neurons to connect and talk to each other by increasing the number and strength of neuronal connections. Astrocytes are involved in neural diseases and are responsible for maintaining a healthy nervous system. The incorporation of astrocytes in the developed model accelerated the connections of the surrounding neurons.
This led to the accelerated maturation of both the astrocytes and the surrounding neurons. The researchers coined these bioengineered mini brains “asteroids” to distinguish them from other types of 3-D sphere cultures called organoids. The system developed allows for mature astrocytes to be developed and have them interact with neurons to a greater extent than before. Unlike other cells in the brain and in the rest of the body, astrocytes have unique properties in humans. They are believed to play a part in the cognitive functions of humans and underlie aspects of human diseases, including Alzheimer’s disease.
The “asteroids” are used to form functional neural circuits where they can be manipulated for understanding disease and developing treatments. The researchers are able to make pluripotent stem cells from any disease or patient and then create mini brains to study the disease process and test drugs. Within five years, the researchers hope to use their system to develop clinical trials to improve or and even possibly regenerate an impaired nervous system.
Reference: Robert Krencik and et al., Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes, Stem Cell Reports, 2017.