Recently, new research focuses on building 3D mini-brains through human pluripotent stem cells being promoted by The Houston Methodist Institute. It will enable researchers to repair the brain or spinal cord neurons damaged by disease or trauma. Robert Krencik, a neuroscientist from Houston Methodist Institute, has developed a new system to reduce the time required to make these brain models with his team. These models can be used to study the mechanisms of disease or drug screening and research. The findings were published in the journal Stem Cell Reports.
‘We always felt like what we were doing in the lab was not precisely modeling how the cells act within the human brain.’ Krencik claimed, ‘So, for the first time, when we put these cells together systematically, they dramatically changed their morphological complexity, size and shape. They look like cells as you would see them within the human brain, so now we can study cells in the lab in a more natural environment.’
What makes this become so important? Krencik said that cells grown in traditional laboratory media are placed in flat culture dishes, the operation methods such as separation and manipulation will interfere with their interactions. Due to these reasons, the results can not reproduce the morphology, structure and differentiation of these cells in the brain, they are just simple, immature cells in the laboratory. However, these cells have a more complex morphology in the human brain, they interact with each other and the surrounding environment in a complex way. The new technology developed by the Krencik team focused on recreating the environment in the brain. They built a 3D culture system, however, and the time spent in these studies was not enough for development acceleration.
Krencik said that ‘Normally, growing these 3-D mini brains takes months and years to develop, We have new techniques to pre-mature the cells separately and then combine them, and we found that within a few weeks they’ re able to form mature interactions with each other. So, the length of time to get to that endpoint for studies is dramatically reduced with our system.’
Krencik’s team focuses on astrocyte research as it is a key factor in the connections and interactions between brain neurons that can increase the amount and intensity of connections between the brain and spinal cord neurons. What’s more, they are involved in many neurological diseases and play an important role in maintaining the health of the nervous system. In a model established with bioengineering by the Krencik team, astrocytes are added to accelerate the connection between peripheral neurons.
Krencik’s team is the first to specifically engineer these astrocytes into 3D mini-brains. The astrocytes and peripheral neurons maturation rate greatly improved with these operations. When they were introduced for the first time in the essay, Krencik referred these engineered mini-brains as “asteroids,” distinguishing them from other types of 3D stereoscopic cultures, such as the organoids we know. The so-called asteroid contains a specific group of astrocytes, while organs have only cells that can not be characterized and quantified.
“Using our system, we can generate mature astrocytes and have them interact intimately with neurons to a greater extent than has been done before,” Krencik said. “Unlike other cells in the brain and in the rest of the body, astrocytes have unique properties in humans. It’s thought they are partly responsible for the unique cognitive functions of humans and also may underlie aspects of human diseases, such as Alzheimer’s and autism spectrum disorders.”
Finally, Krencik used these “asteroids” to make up functional neural circuits. In this way, researchers can develop therapies through experimental procedures and explain the causes of the disease. Krencik says they can create induced pluripotent stem cells, which is referred as “IPS cells,” and then forming the 3D mini-brain to study the procedure of disease and screen drugs in the process of medication. We will look forward to the further development and application of this study.