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On Multicell-Interaction Chip: In Situ Observing the Interactions between the Astrocytes with Lysosomal Dysfunction
Yimeng Zhao1, Chen Zhang1, Chaohui Liang1
1School of Medical Technology, Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, China.
Analytical Chemistry
|December 6, 2024
Summary
Researchers developed a new in vitro model using a microfluidic chip and a photosensitizer to study how astrocyte lysosomal dysfunction impacts blood-brain barrier cells. This model reveals reactive oxygen species and exosomes mediate damage, advancing brain-vascular interaction research.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Cell Biology
Background:
- Lysosomes in astrocytes are crucial for clearing toxic proteins in the brain.
- Lysosomal dysfunction contributes to neurodegenerative diseases by causing protein aggregation and damaging neurons and the blood-brain barrier (BBB).
- Studying astrocyte-BBB cell interactions under lysosomal dysfunction is vital but limited by the lack of suitable in vitro models.
Purpose of the Study:
- To develop and validate an advanced in vitro model for investigating the complex interactions between astrocytes with lysosomal dysfunction and BBB cells.
- To utilize a novel lysosome-targeted photosensitizer for inducing controlled oxidative stress in astrocytes within the model.
- To observe and analyze the secondary injuries to BBB cells resulting from astrocyte lysosomal dysfunction.
Main Methods:
- Introduction of an 8-well arrayed microfence multicell interculture chip (AMMIC) with a hydrophilic surface for co-culturing astrocytes and BBB cells.
- Synthesis and application of a novel lysosome-targeted photosensitizer (IVQ-2Br) to induce controlled oxidative stress and lysosomal damage in astrocytes.
- In situ observation and analysis of cellular responses and intercellular communication mediators using the integrated AMMIC and photosensitizer system.
Main Results:
- Successfully constructed a model to study astrocyte lysosomal dysfunction and its effects on BBB cells.
- Observed severe secondary injuries to BBB cells, including morphological changes, reduced activity, and DNA damage, induced by astrocyte oxidative stress.
- Identified reactive oxygen species (ROS) and exosomes as key mediators of intercellular communication in this oxidative stress-induced injury.
Conclusions:
- The developed AMMIC combined with IVQ-2Br provides an effective in vitro platform for studying astrocyte-BBB cell interactions under conditions of lysosomal dysfunction.
- The findings highlight the significant role of ROS and exosomes in mediating BBB damage secondary to astrocyte lysosomal dysfunction.
- This integrated approach demonstrates the potential of advanced microfluidic devices and targeted photosensitizers for future biomedical research on neurovascular interactions and diseases.
