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Related Concept Videos

Chemical Synapses01:26

Chemical Synapses

Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
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A modular platform to generate functional sympathetic neuron-innervated heart assembloids.

Nadja Zeltner1, Hsueh-Fu Wu1, Kenyi Saito-Diaz1

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Researchers developed human sympathetic cardiac assembloids (hSCAs) by co-culturing sympathetic neurons with cardiac organoids. These innervated cardiac models exhibit mature structures and functional neural regulation, advancing disease modeling and drug discovery.

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Area of Science:

  • Stem cell biology
  • Neuroscience
  • Cardiovascular research

Background:

  • Human pluripotent stem cell (hPSC)-based organoids are crucial for studying development, disease, and drug discovery.
  • Most current organoids lack innervation, limiting their ability to model neural regulation of organ function and tissue maturation.
  • The autonomic sympathetic nervous system plays a vital role in regulating cardiac function.

Approach:

  • Developed a bioengineering-free method to create sympathetic neuron (symN)-innervated cardiac assembloids (hSCAs).
  • Utilized human pluripotent stem cells to generate both cardiac and sympathetic neuron components.
  • Integrated symNs with cardiac assembloids to achieve functional neural innervation.

Key Points:

  • hSCAs exhibit mature cardiac muscle structures, atrial-to-ventricular patterning, and spontaneous beating.
  • Innervating symNs demonstrate neurotransmitter synthesis and pharmacologically/optogenetically controllable regulation of cardiac beating rate.
  • Successfully modeled symN-mediated cardiac development and myocardial infarction in the hSCA system.

Conclusions:

  • hSCAs provide a novel, versatile platform for studying neuro-cardiac interactions and modeling cardiac diseases.
  • This model system is suitable for future neurocardiotoxicity screening and can be adapted for other organoid-neuronal combinations.
  • The modular nature allows for interchangeable neuron and organoid types, expanding research possibilities.