Developing a 3D cerebrovascular barrier model...Help in the Study of Neurodegenerative Diseases
Jan 22, 2025
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This model utilizes 3D bioprinting technology to reproduce the cerebrovascular barrier more precisely than conventional 2D models, and is expected to play an important role in the study of neurodegenerative diseases and the development of new treatments.
The cerebrovascular barrier serves as an important protective layer located between the brain and blood vessels. This barrier protects the brain from harmful substances and provides the necessary nutrients and oxygen. However, in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), the cerebrovascular barrier is damaged or inflammation occurs, which exacerbates the disease. To understand this and find effective treatment methods, a more accurate cerebrovascular barrier model was needed.
Professor Baek Sun-ha of Seoul National University Hospital and Professor Jang Jin-ah of POSTECH (Dr. Han Ho-hyun) developed a '3D bioink' that can accurately reproduce the cerebrovascular barrier by utilizing a decellularized extracellular matrix (CBVdECM). This bioink is an extracellular matrix derived from the brain and blood vessels of pigs and can reproduce the properties of the cerebrovascular barrier well.
The research team used this bio-ink to create a human cerebrovascular barrier structure with a 3D printer. Through the tubular structure, cells self-assembled to form a double-layer structure, and the actual human cerebrovascular barrier could be implemented very similarly. In this process, brain microvascular endothelial cells and perivascular cells play an important role, endothelial cells form the inner wall of blood vessels, and surrounding cells play a role.
Using the newly developed 3D BBB model, the research team observed changes when the cerebrovascular barrier interacts with inflammatory substances (TNF-α, IL-1β). As a result, it was possible to reproduce an important process in which the inflammatory response affects the cerebrovascular barrier and exacerbates neurodegenerative diseases. By identifying the process by which inflammatory substances increase the permeability of BBB, and harmful substances penetrate the brain or deteriorate the inflammatory response, we demonstrated that the cerebrovascular barrier plays an important role in neuroinflammatory and disease progression.
In addition, the arrangement and organization process of closely linked proteins (VE-cadherin), which were not observed in the existing 2D model, could be clearly reproduced through the 3D model. VE-cadherin is an important protein that aids cell-to-cell linkage and maintains the durability and functionality of the cerebrovascular barrier. The team was able to better understand how VE-cadherin regulates the permeability of the cerebrovascular barrier through this model, and provided important information on changes in BBB function in inflammatory diseases.
Professor Baek Sun-ha (neurosurgery) of Seoul National University Hospital said, `The newly developed 3D BBB model reproduces the cerebrovascular barrier that is more sophisticated and close to reality than the existing 2D model, and allows us to better understand the role of neuroinflammatory in neurodegenerative diseases.'"We expect this to be of great help in the mechanism of neurodegenerative diseases and the development of new treatments.'
Professor Jang Jin-ah of POSTECH (Mechanical Engineering Department, Biotechnology Department, IT Convergence Engineering Department, Graduate School of Convergence Engineering) said "In the future, we plan to develop more precise inflammatory response and BBB permeability quantification technology by integrating glial cells, neurons, and immune cells, and expand patient-specific disease models."
Meanwhile, the study was conducted with the support of the Ministry of Trade, Industry and Energy, the Korea Institute of Industrial Technology Evaluation and Management, and the Korea Research Foundation, and was published in the recent issue of the international journal 『Biomaterials Research』.
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This article was translated by Naver AI translator.
