An organoid model for human cerebellar development and disease: Pioneered by USC Stem Cell team

Developmental Phase

There once was a significant problem for scientists. They were particularly interested in the growth and development of the human brain in relation to disorders like Parkinson's and Alzheimer's. But, because to the differences in human brain structure, animal models could not be used. Thus, a new approach to studying the human brain needs to be developed.

That's when they found out about organoids. These resemble little brains developed in a lab! Their development from stem cells results in 3D models that resemble and function like actual human brains.

These organoids allow scientists to observe how the brain develops and how diseases impact it. Even more precise alterations can be added to observe the results.

The fact that they can create organoids from specific patients, however, is the coolest part. This implies that each organoid is distinct from the person from whom it originated.

Additionally, researchers can discover novel treatments and gain a better understanding of how diseases function by examining these organoids.

Thus, through the integration of organoids, patient studies, and animal models, scientists are gaining a deeper understanding of the functioning and maintenance of the brain than ever before.

Organoids, which are made from stem cells, are miniature, 3D replicas of organs or tissues that mimic the structure and operations of their in vivo counterparts by self-organizing and differentiating into three-dimensional cell masses.

The cerebellum is a region of the hindbrain that is primarily composed of two cell types : granule cells and Purkinje neurons. The laboratory of Giorgia Quadrato, an assistant professor of stem cell biology and regenerative medicine, has developed a novel human brain organoid model that generates all major cell types of the cerebellum, which is a first for USC Stem Cell scientists.

It has never been possible for scientists to generate Purkinje cells in an all-human system that have the chemical and electrical characteristics of functioning neurons. The journal Cell Stem Cell recently revealed these advances in organoid-directed brain simulation.

The lack of a human cell-based system that can replicate the cellular variety and functional characteristics of the human cerebellum has slowed research on human cerebellar development.

In the study, they presented a human organoid model called human cerebellar organoids (hCerOs), which is able to create the rich cellular variety of the embryonic cerebellum.

Among these is a population of rhombic lip progenitor cells that is specific to humans and has never been developed in vitro before.

In addition to developing unique cytoarchitectural characteristics, such as laminar directed layering, two-month-old hCerOs establish functional connections between excitatory and inhibitory neurons that show coordinated network activity.

A long-standing problem in the area is resolved by the long-term culture of hCerOs, which permits the optimal survival and maturation of Purkinje cells that exhibit the molecular and electrophysiological features of their in vivo counterparts.

Stem cells are used to generate brain organoids, which can replicate the functioning of several brain regions, including the cortex, retina, and cerebellum.

Even if it might appear to be a little fantasy, this technology is being utilized more and more to learn more about neurological diseases and ultimately provide better treatments.

In his study Quadrato, explains that in a human organoid model, the primary cell types of the developing cerebellum co-develop and mature in a repeatable manner, offering a novel avenue for investigating the underlying biology of cerebellar development and diseases and advancing therapeutic approaches.

In addition to regulating movement, the cerebellum is involved in language, memory retention, geographic processing, executive functioning, and handling emotions, among other aspects of cognition.

Numerous neurodevelopmental and neurodegenerative conditions, such as autism spectrum disorder and cerebellar ataxia, an illness that impairs muscle function, are caused by Purkinje cell deterioration.

Apart from the excitatory neurons that exchange information, the inhibitory neurons in the organoids also established circuits and exhibited coordinated network activity, indicating that they were nerve cells with function.

The terminal brain tumor in children, medulloblastoma, can be attributed to organoids that produced human-specific progenitor cells. Because of this, the organoids provide a helpful model for researching and developing a cure for this type of malignancy in children.

The organoids might also be persuaded to generate layers and other biological characteristics that mimic typical embryonic neural growth if they were given the appropriate external signals.

A foundation for the advancement of cutting-edge treatments for a range of illnesses is established by the organoid models.

First author of the Cell Stem Cell study and PhD candidate at the Quadrato Lab, Alexander Atamian remarked, "This study provides a physiologically significant all-human model system to clarify the cell type-specific mechanisms governing cerebellar development and disease." 

Check out the Science Friday segment  that highlights this study:

https://www.sciencefriday.com/segments/brain-organoids/.