Succeeds in Developing Spinal-Cord Organoids Recapitulating Neural-Tube Morphogenesis
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Date Modified Date : 2022.06.16
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Research Team Led by Professor Woong Sun of KU College of Medicine Succeeds in Developing Spinal-Cord Organoids Recapitulating Neural-Tube Morphogenesis

It is getting close to predict and prevent neural tube defects, one of the main congenital developmental disorders.

A research team led by Professor Woong Sun from the Department of Anatomy at KUCM succeeded in producing spinal-cord organoids that simulate neural tube formation, proving the potential for using organoid-based drug screening platforms.

Under the leadership of Professor Sun's team, the research was conducted in collaboration with a number of institutions, including teams led by Dr. Il-joo Cho from the Korea Institute of Science and Technology, Sang-hyuk Lee from Ewha Womans University, and InterMinds (CEO, Jong-jin Kim), an AI venture firm.

An organoid is a miniaturized and simplified version of an organ produced in vitro from stem cells. Because organoids are generated through the process resembling to the in vivo development, they also show realistic micro-anatomy. Since animal testing has clear limitations when it comes to studying human disease mechanisms and developing new drugs as well as ethical concerns, organoids have emerged as a better alternative that can be used to meet different purposes in various fields, such as exploring human developmental processes, identifying the causes of diseases, developing new drugs, and forecasting side effects.

Neural tube defects are one of the most common types of congenital deformities and are found in about 300,000 fetuses worldwide each year. The neural tube is an early developmental tissue that gives rise to the central nervous system, which is composed of the brain and spinal cord, and the tube-forming early morphogenic process is unique and differs from that of other tissues.

During fetal development, certain cells located on the back of the embryo change shape and begin to form the neural tube. This process is called neural tube formation or neurulation, and failure of this process may cause an abnormal neural tube folding, a neural tube defect, one of the most common congenital developmental disorders. In humans, the neural tube formation process takes place during the third week of pregnancy, making it extremely difficult to study the human-specific neural tube morphogenesis process as well as its mechanisms and abnormal folding prevention methods.

Launched in 2015 to develop spinal-cord organoids, Professor Sun's team established a method of producing spinal-cord organoids that mimic neural tube formation, and the team went through a process to verify that the organoids are similar to actual human spinal cord tissues through the analysis of histology, transcription, and electrophysiology. A verification test also confirmed that the manufacturing technology performs well in terms of reproducibility and quantification, which are important factors in the application of organoids to clinical technology.

In particular, the combination of stem cell culture technology, the latest 3D imaging technology, and deep learning artificial intelligence technology enabled high-throughput screening (HTS), and as a result, drug reactivity to thousands of organoids was verified quickly and efficiently.

The research team selected a total of six types of anticonvulsants, including a group of dangerous drugs that increased the likelihood of neural tube defects when administered in pregnant women, and conducted neural tube defect modeling. In the test, abnormal morphogenesis and neural tube structures were observed only in the risk drug treatment group, which was similar to the reports of previous clinical studies. Thus, the team successfully verified that the spinal-cord organoid model could be used in a lab as a toxicology test.

Professor Sun said, "The spinal-cord organoid our team developed can support preclinical study of drug development and proves the potential for using an organoid-based platform to improve the efficiency of drug safety tests. Now we can make models for not only neural tube deficiency, but also various brain diseases."

This study was conducted as a project of the National Research Foundation of Korea with support from the Ministry of Science and ICT. The study was published in the latest issue (March 28) of Nature's sister magazine, Nature Biomedical Engineering, under the title "Production of human spinal-cord organoids recapitulating neural-tube morphogenesis."

Professor Sun graduated from Seoul National University in 1991 and received master's and doctorate degrees from the same school. He studied at Osaka University in Japan and Wake Forest University in the United States, and he has been teaching at the KUCM Department of Anatomy since 2002. He was the dean in charge of research exchange at Korea University and is currently serving as the general director of the Asia-Pacific Society for Neurochemistry and editor-in-chief of the International Journal of Stem Cells. He won the 2017 Korea University Friendship Association’s Academic Award and the 18th Pfizer Medical Award in 2020. In 2021, his book, I Want to Make a Brain, a record of his organoid research, was published, and his study was selected in 2018 by the Korea University Medical Center as one of the "Top 10 Future Medicine Technologies" that will lead the next generation of biomedical development.