Modeling Sympathetic Neuro-Cardiac Interactions in a hiPSC-Based Microphysiological System

Area of Science:

• Cardiovascular Research
• Neuroscience
• Biomedical Engineering

Background:

• The cardiac autonomic nervous system regulates heart function but studying it is challenging.
• Existing experimental models for human heart-neuron interactions are limited.

Purpose of the Study:

• To develop a novel microphysiological system for studying neuro-cardiac interactions.
• To create a reliable model for investigating cardiac disorders and arrhythmias.

Main Methods:

• Utilized a compartmentalized microfluidic device (MFD) to co-culture human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) and sympathetic neurons (hiPSC-SNs).
• Characterized hiPSC-SNs for neuronal markers and functional maturity using imaging, RT-qPCR, and patch-clamp electrophysiology.
• Assessed functional integration by monitoring hiPSC-CMs' action potential frequency and beating rate after co-culture and pharmacological stimulation.

Main Results:

• hiPSC-SNs exhibited mature neuronal characteristics and functional responses.
• Axonal projections from hiPSC-SNs successfully connected with hiPSC-CMs within the MFD.
• Co-culture led to increased hiPSC-CMs' action potential frequency and beating rate, modulated by nicotine and propranolol.

Conclusions:

• Demonstrated the successful differentiation of hiPSCs into functional sympathetic neurons.
• Established a robust neuro-cardiac interface using the MFD platform.
• The microphysiological system is a valuable tool for disease modeling and drug screening for neuro-cardiac disorders.