Scientists have pioneered the creation of 3D mini-organs using human fetal brain tissue, resulting in self-organizing structures with immense potential for studying brain development. This breakthrough not only provides a unique avenue for understanding the intricacies of the brain but also offers a valuable tool for investigating diseases related to brain development, including brain tumors.
Traditionally, scientists utilized various methods, such as cell lines and laboratory animals, to model healthy tissue and diseases. In recent years, 3D mini-organs, known as organoids, have gained popularity due to their ability to closely mimic organ functions in a laboratory setting.
Unlike previous approaches where brain organoids were cultivated from embryonic or pluripotent stem cells, the team at the Princess Máxima Center for pediatric oncology and the Hubrecht Institute in the Netherlands opted for a different method. They developed brain organoids directly from small pieces of human fetal brain tissue, and to their surprise, these pieces spontaneously self-organized into intricate 3D structures, roughly the size of a grain of rice.
The brain organoids maintained a complex 3D composition, comprising various types of brain cells, including outer radial glia—a cell type present in humans and our evolutionary ancestors. This closely mirrored the human brain's characteristics, allowing for more accurate studies.
Moreover, the brain organoids produced extracellular matrix proteins, which acted as a scaffolding around cells. This unique feature contributed to the self-organization of the brain tissue into 3D structures. The presence of the extracellular matrix also opens up opportunities to study the environment of brain cells and explore deviations from normal conditions.
These tissue-derived organoids retained characteristics specific to the region of the brain from which they originated. They responded to signaling molecules crucial in brain development, hinting at their potential to unravel the complex molecular network involved in directing brain development.
Intriguingly, the researchers delved into the organoids' application in modeling brain cancer. By introducing faults in the TP53 cancer gene, they observed the cells with defective TP53 outgrowing healthy cells, mimicking a typical feature of cancer cells. Using gene-editing techniques, the team also explored the response of these mutant organoids to existing cancer drugs, showcasing the potential for advancing cancer drug research.
The tissue-derived organoids exhibited robust growth over six months, and the researchers could multiply them, ensuring reproducibility in experiments. This opens new avenues for studying brain-related diseases and potential treatments.
Moving forward, the researchers aim to explore further applications of their tissue-derived brain organoids and collaborate with bioethicists to guide their ethical development and use. This innovative approach promises to deepen our understanding of human brain development and offers a valuable tool for researching neurological disorders and childhood brain cancer.
Link to the research: Human fetal brain self-organizes into long-term expanding organoids
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