Breakthrough 3D Model Reveals New Insights into Alzheimer’s and Blood-Brain Barrier

Exciting developments in the field of neuroscience have arisen from collaborative research led by Professor Jinah Jang at POSTECH and Professor Sun Ha Paek at Seoul National University Hospital.

Their teams have successfully created a cutting-edge three-dimensional model designed to replicate the Blood-Brain Barrier (BBB).

This pioneering research is detailed in the journal Biomaterials Research, which specializes in materials science.

Understanding Neurodegenerative Diseases

Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), are marked by the gradual decline of brain and nervous system functions.

Often aggravated by aging, these disorders are significantly fueled by chronic neuroinflammation.

This condition stems from intricate interactions between cerebral blood vessels and neural cells, with the BBB serving a pivotal role in regulation.

Unfortunately, existing BBB models have struggled to accurately depict the complex three-dimensional architecture of cerebral blood vessels, posing challenges for research and drug development.

Advancements in 3D Bioprinting Technology

To tackle these issues, the research team developed a specialized bioink known as “decellularized extracellular matrix” (CBVdECM), derived from porcine brains and blood vessels.

They skillfully combined this bioink with state-of-the-art 3D bioprinting technology to craft a tubular vascular model that authentically captures the anatomical features and functional capabilities characteristic of the human BBB.

One of the standout accomplishments of this model is its ability to encourage the spontaneous formation of a dual-layered structure without any external intervention.

By integrating human brain microvascular endothelial cells (HBMEC) and human brain vascular pericytes (HBVP) into the CBVdECM bioink during printing, the endothelial cells naturally assembled to form the inner vascular wall, while the pericytes organized into an outer layer.

This process led to the creation of a dual-layer architecture that closely mimics real blood vessels.

Implications for Future Research

Furthermore, the research team excelled at recreating the organization and development of tight junction proteins, which are typically absent in traditional two-dimensional models.

They also successfully demonstrated BBB permeability and the inflammatory responses triggered by pro-inflammatory agents like TNF-α and IL-1β.

This approach provided a detailed framework for understanding neuroinflammatory pathways, shedding light on how BBB dysfunction and inflammation contribute to the progression of neurodegenerative diseases.

Professor Sun Ha Paek emphasized that this study provides a crucial platform for investigating the underlying mechanisms of neuroinflammation, opening doors for new therapeutic possibilities.

Meanwhile, Professor Jinah Jang expressed a desire to incorporate additional cell types, such as glial cells, neurons, and immune cells.

This enhancement would not only allow for a more precise evaluation of inflammatory responses and permeability but also facilitate the development of patient-specific disease models.

This significant research initiative received backing from the Ministry of Trade, Industry & Energy, as well as the Korea Planning & Evaluation Institute of Industrial Technology’s Industrial Technology Alchemist Project.

The University-Focused Research Institute Support Program, provided by the National Research Foundation of Korea, also played a vital role in facilitating this groundbreaking study.

Source: ScienceDaily