People Establish a New Blood-brain Barrier Model to Probe Metastatic Brain Tumors

The blood-brain barrier (BBB) is a physiological barrier between blood and brain tissue. It is essential to maintain the steady of the microenvironment of the central nervous system and physiological activity in the brain. The studies shows that abnormal of blood-brain barrier function are closely related to the Alzheimer's disease, brain tumor and Parkinson's disease.

However, the compact structure and high selective of blood-brain barrier makes it impossible of most drug molecules to enter the brain, which greatly limits the research and development of the central nervous system drugs. It is becoming a key problem to solve the lack of significant of existing two-dimensional cellular culture and animal models in vivo, by establishing effective and reliable BBB models.

The Microfluidic Research Group led by Prof. QIN Jianhua in DICP proposed a new and dynamic in vivo-like three-dimensional microfluidic system. The system can replicate the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors.

Schematic of the integrity of blood-brain barrier and brain metastasis (Imaged by XU Hui)

In this system, the complex BBB microenvironment is reproduced via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

The related results were published on Scientific Reports (DOI: 10.1038/srep36670). This work was supported by the natural science foundation of China and the international cooperation project of the Ministry of science and technology. (Text and Imaged by XU Hui)