A laboratory study evaluated a compartmentalized microfluidic co-culture of cardiomyocytes, heart cells derived from human induced pluripotent stem cells, and sympathetic nerve cells as a model of neuro-cardiac interactions. The preprint reports that the two cell types formed a physical connection, while activity in the cardiomyocytes changed in response to nicotine and propranolol. The authors describe the system as a feasible platform for disease modeling and pharmacological screening.
Two chambers, one model
The device contained two wide-open chambers separated by microfluidic microchannels. The two populations were co-cultured in that compartmentalized layout, with cardiomyocytes in one chamber and sympathetic neurons in the other. One functional test applied nicotine in the neuronal chamber and tracked cardiomyocyte action-potential frequency and beating rate.
Signs of a working connection
The study reports expression of peripherin, tyrosine hydroxylase, β-tubulin III, dopamine β-hydroxylase and nicotinic acetylcholine receptors in the sympathetic neurons. Neither quantitative expression values nor replicate information are reported for this marker result.
Patch-clamp assessment showed that the neurons generated spontaneous action potentials and responded positively to nicotine at 1 µM. In plain language, they showed spontaneous electrical activity and a nicotine response. The size and precision of that electrophysiological response were not reported.
Axons from the neurons were reported to project into the cardiomyocyte chamber, and the abstract describes a physical connection between the two cell types.
After 10 days of co-culture, the abstract reports a significant increase in cardiomyocyte action-potential frequency and beating rate. Researchers measured those endpoints with patch-clamp recordings and video motion tracking. The report calls the change significant but provides no effect estimate or uncertainty measure.
The model responded to two compounds
Nicotine application in the neuronal chamber was reported to accelerate cardiomyocyte action-potential frequency and beating rate. The magnitude and statistical uncertainty of that response are not reported.
In a separate test, administration of propranolol at 5 µM was reported to decrease beating rates. The magnitude and statistical uncertainty of that decrease are not reported.
A platform result with clear limits
The authors describe the work as a feasibility demonstration for differentiating induced pluripotent stem cells into functional sympathetic neurons and establishing a neuro-cardiac interface for disease modeling and pharmacological screening. That makes the result laboratory platform evidence from a cell co-culture, not a report of treatment effects in patients or intact human hearts. The model does not establish that these cellular responses reproduce the way autonomic nerves and the heart work together in an intact human body, or that they predict clinical treatment effects.
The report's main numerical limitation is that the abstract calls the cardiomyocyte functional change significant but gives no effect estimate or uncertainty measure. It also does not report the magnitude and precision of the neuronal, nicotine or propranolol responses.
The document is labeled a preprint and states that it has not yet been peer reviewed by a journal. The record says the full text is available from the preprint server.
Paper data and sources
Original title: Modeling sympathetic neuro-cardiac interactions in a hiPSC-based microphysiological system.
Authors: Jean-Baptiste Reisqs, Yvonne Sleiman, Mohamed Boutjdir
Journal/Repository: Lab on a chip
Status: Peer-reviewed
First online: 2026-09-29
DOI: 10.1039/d6lc00320f
Original paper