3D Multi-Tissue microphysiological system for Anti-Cancer and cardiotoxicity drug screening with automated image...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Pharmacology

Background:

• Microphysiological systems (MPS) offer controlled in vitro environments for studying cellular responses.
• 3D tissue models are crucial for mimicking in vivo conditions and improving drug efficacy studies.
• Current methods for evaluating chemotherapy effects in complex tissues require refinement.

Purpose of the Study:

• To develop and validate a novel 3D microfluidic system for in vitro chemotherapy drug efficacy testing.
• To model aggressive malignancies like breast cancer and glioblastoma, and assess chemotherapy-induced cardiotoxicity.
• To integrate automated image analysis for quantitative assessment of cellular changes in response to treatment.

Main Methods:

• Development of a dual-chamber, closed-capillary circuit microfluidic platform for 3D tissue culture.
• Co-culture of HER2+ breast cancer and cardiac cells, and a glioblastoma model within the MPS.
• Utilized a Python-based automated image analysis script (AIAPS) for quantifying cell size from 3D fluorescence images.

Main Results:

• The 3D MPS maintained lineage-specific biomarker expression and physiologically relevant cell morphology.
• Demonstrated detectable changes in cell sizes following chemotherapy treatment in the tissue models.
• Successfully modeled chemotherapy-induced cardiotoxicity and glioblastoma drug response in vitro.

Conclusions:

• The developed 3D MPS is a versatile and effective platform for preclinical drug screening.
• The system enables reproducible quantification of cellular responses to chemotherapeutic agents.
• This technology holds promise for advancing personalized medicine and reducing drug development costs.