Human Neurons Form Axon-Mediated Functional Connections with Human Cardiomyocytes in Compartmentalized Microfluidic...

Area of Science:

• Cardiovascular Biology
• Neuroscience
• Biomedical Engineering

Background:

• The cardiac autonomic nervous system (cANS) is crucial for heart function, with its development involving neuron-cardiomyocyte (CM) comaturation.
• Dysfunction of the cANS can lead to fatal cardiac conditions, highlighting the need for advanced models.
• Existing neuron-CM coculture models often lack fully human cell systems and functional interaction studies.

Purpose of the Study:

• To develop a novel, completely human cell-based cardiac innervation model on a chip.
• To create a platform for studying embryogenesis, cardiac diseases, and drug screening.
• To investigate functional, electrophysiological neuron-CM interactions in a controlled microenvironment.

Main Methods:

• Utilized a compartmentalized microfluidic device, the 3D3C chip, for culturing human induced pluripotent stem cell (hiPSC)-derived neurons and CMs.
• Enabled axonal growth between compartments via microtunnels, mimicking in vivo cardiac innervation.
• Employed immunocytochemistry, RT-qPCR, and video microscopy for comprehensive analysis.

Main Results:

• Demonstrated a functional cardiac innervation model using only hiPSC-derived human cells.
• Showcased electrophysiologically functional axon-mediated interactions between hiPSC-neurons and hiPSC-CMs.
• Validated the model's ability to mimic in vivo neuron-CM communication through CM beating response assays.

Conclusions:

• The 3D3C chip provides a robust platform for studying human cardiac innervation.
• This novel model facilitates research into neuron-CM interactions relevant to cardiac development and disease.
• The system supports diverse analytical techniques, offering a versatile tool for cardiac research and drug discovery.