A research team at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan report they have created a model of the blood-brain barrier using modularized tissue derived from human cells. The “Tissue-in-a-CUBE” is a small cubic structure that could improve the drug discovery field and be used as an alternative to animal models in preclinical studies.
The findings are published in Communications Biology in the article titled, “Modular Tissue-in-a-CUBE platform to model blood-brain barrier (BBB) and brain interaction.”
To construct the blood-brain barrier model, the research team led by Masaya Hagiwara, PhD, at RIKEN BDR, created 5-mm CUBE frames, filled them with hydrogel embedded with astrocytes and pericytes derived from the human brain, and seeded vascular endothelial cells differentiated from human induced pluripotent stem (iPS) cells onto the surface to form cell sheets. They then tested the device. According to Hagiwara, “We were happy to find that it accurately mimicked the real blood-brain barrier in terms of structure and function: with astrocytes and pericytes extending three-dimensionally beneath the sheet of endothelial cells, and that like the real barrier, it only allowed limited substances to pass through.”
The CUBE frame can be manipulated with forceps, allowing convenient handling of the blood-brain barrier model, with cell culturing being performed in a regular cell-culture plate. After maturation, the tissue was integrated with other prepared tissues in a fluidic chip to analyze inter-tissue interactions, thus fitting into the previously established modular Tissue-in-a-CUBE platform.
To demonstrate the usefulness of the system for drug development, the group conducted drug screening experiments. Brain tumor cells were cultured in the CUBE container to prepare a brain tumor module. The blood-brain barrier and brain tumor modules were then transferred into a fluidic chip and connected. This setup allowed researchers to verify how much of an anticancer drug could pass through the barrier, reach the brain tumor, and exert its effect.
“This innovative approach offers a promising alternative to animal testing for essential drug development tests, involving the understanding of drug behavior, effectiveness, and safety,” said Hagiwara. “Our modularized platform could be adapted for various diseases, including age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. In the future we plan to modularize and replicate connections between different organoids.”
