ArticleInternational journal of molecular sciences2022
Human Neurons Form Axon-Mediated Functional Connections with Human Cardiomyocytes in Compartmentalized Microfluidic Chip.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Innervated human cardiac muscle model reveals sympathetic drivers of KCNH2-associated arrhythmias.Nature communications · 2026Article
- Induced Pluripotent Stem Cell-Based Platforms for Cardiac-Related Pain Research: Molecular Mechanisms, Experimental Models, and Therapeutic Applications.International journal of molecular sciences · 2026Review
- A reproducible and physiologically relevant human iPSC-derived platform for in vitro modeling of the neurocardiac junction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Modeling embryonic heart vascular plexus development and sympathetic innervation on a human heart organoid.iScience · 2026Article
- A narrative review of spatial multi-omics and organ-on-a-chip technologies for cardio-cerebral-renal crosstalk.Frontiers in bioengineering and biotechnology · 2026Review
- Development and modeling of cardiac autonomic innervation.Nature cardiovascular research · 2025Review
- Brain organoids-on-chip for neural diseases modeling: History, challenges and trends.Journal of pharmaceutical analysis · 2025Review
- Modeling neuroinflammatory interactions between microglia and astrocytes in a human iPSC-based coculture platform.Cell communication and signaling : CCS · 2025Article
- Role of Cav1.3 Channels in Brain-Heart Interactions: An Unexpected Journey.Biomedicines · 2025Review
- Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.The Journal of physiology · 2025Review
- Microfluidic platforms for monitoring cardiomyocyte electromechanical activity.Microsystems & nanoengineering · 2025Review
- Hyaluronic Acid-Based 3D Bioprinted Hydrogel Structure for Directed Axonal Guidance and Modeling Innervation In Vitro.Advanced healthcare materials · 2025Article
- Advancing organ-on-chip systems: the role of microfluidics in neuro-cardiac research.Current research in pharmacology and drug discovery · 2025Review
- Building blocks of microphysiological system to model physiology and pathophysiology of human heart.Frontiers in physiology · 2023Review
- Experimental models to study osteoarthritis pain and develop therapeutics.Osteoarthritis and cartilage open · 2022Review
- Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies.Cells · 2022Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The cardiac autonomic nervous system (cANS) regulates cardiac function by innervating cardiac tissue with axons, and cardiomyocytes (CMs) and neurons undergo comaturation during the heart innervation in embryogenesis. As cANS is essential for cardiac function, its dysfunctions might be fatal; therefore, cardiac innervation models for studying embryogenesis, cardiac diseases, and drug screening are needed. However, previously reported neuron-cardiomyocyte (CM) coculture chips lack studies of functional neuron-CM interactions with completely human-based cell models. Here, we present a novel completely human cell-based and electrophysiologically functional cardiac innervation on a chip in which a compartmentalized microfluidic device, a 3D3C chip, was used to coculture human induced pluripotent stem cell (hiPSC)-derived neurons and CMs. The 3D3C chip enabled the coculture of both cell types with their respective culture media in their own compartments while allowing the neuronal axons to traverse between the compartments via microtunnels connecting the compartments. Furthermore, the 3D3C chip allowed the use of diverse analysis methods, including immunocytochemistry, RT-qPCR and video microscopy. This system resembled the in vivo axon-mediated neuron-CM interaction. In this study, the evaluation of the CM beating response during chemical stimulation of neurons showed that hiPSC-neurons and hiPSC-CMs formed electrophysiologically functional axon-mediated interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.