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Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies
In the heart, cardiac function is regulated by the autonomic nervous system (ANS) that extends through the myocardium and establishes junctions at the sinus node and ventricular levels. Thus, an increase or decrease in neuronal activity acutely affects myocardial function and chronically affects its...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737466/ https://www.ncbi.nlm.nih.gov/pubmed/36497024 http://dx.doi.org/10.3390/cells11233764 |
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author | Bernardin, Albin A. Colombani, Sarah Rousselot, Antoine Andry, Virginie Goumon, Yannick Delanoë-Ayari, Hélène Pasqualin, Côme Brugg, Bernard Jacotot, Etienne D. Pasquié, Jean-Luc Lacampagne, Alain Meli, Albano C. |
author_facet | Bernardin, Albin A. Colombani, Sarah Rousselot, Antoine Andry, Virginie Goumon, Yannick Delanoë-Ayari, Hélène Pasqualin, Côme Brugg, Bernard Jacotot, Etienne D. Pasquié, Jean-Luc Lacampagne, Alain Meli, Albano C. |
author_sort | Bernardin, Albin A. |
collection | PubMed |
description | In the heart, cardiac function is regulated by the autonomic nervous system (ANS) that extends through the myocardium and establishes junctions at the sinus node and ventricular levels. Thus, an increase or decrease in neuronal activity acutely affects myocardial function and chronically affects its structure through remodeling processes. The neuro–cardiac junction (NCJ), which is the major structure of this system, is poorly understood and only a few cell models allow us to study it. Here, we present an innovant neuro–cardiac organ-on-chip model to study this structure to better understand the mechanisms involved in the establishment of NCJ. To create such a system, we used microfluidic devices composed of two separate cell culture compartments interconnected by asymmetric microchannels. Rat PC12 cells were differentiated to recapitulate the characteristics of sympathetic neurons, and cultivated with cardiomyocytes derived from human induced pluripotent stem cells (hiPSC). We confirmed the presence of a specialized structure between the two cell types that allows neuromodulation and observed that the neuronal stimulation impacts the excitation–contraction coupling properties including the intracellular calcium handling. Finally, we also co-cultivated human neurons (hiPSC-NRs) with human cardiomyocytes (hiPSC-CMs), both obtained from the same hiPSC line. Hence, we have developed a neuro–cardiac compartmentalized in vitro model system that allows us to recapitulate the structural and functional properties of the neuro–cardiac junction and that can also be used to better understand the interaction between the heart and brain in humans, as well as to evaluate the impact of drugs on a reconstructed human neuro–cardiac system. |
format | Online Article Text |
id | pubmed-9737466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97374662022-12-11 Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies Bernardin, Albin A. Colombani, Sarah Rousselot, Antoine Andry, Virginie Goumon, Yannick Delanoë-Ayari, Hélène Pasqualin, Côme Brugg, Bernard Jacotot, Etienne D. Pasquié, Jean-Luc Lacampagne, Alain Meli, Albano C. Cells Article In the heart, cardiac function is regulated by the autonomic nervous system (ANS) that extends through the myocardium and establishes junctions at the sinus node and ventricular levels. Thus, an increase or decrease in neuronal activity acutely affects myocardial function and chronically affects its structure through remodeling processes. The neuro–cardiac junction (NCJ), which is the major structure of this system, is poorly understood and only a few cell models allow us to study it. Here, we present an innovant neuro–cardiac organ-on-chip model to study this structure to better understand the mechanisms involved in the establishment of NCJ. To create such a system, we used microfluidic devices composed of two separate cell culture compartments interconnected by asymmetric microchannels. Rat PC12 cells were differentiated to recapitulate the characteristics of sympathetic neurons, and cultivated with cardiomyocytes derived from human induced pluripotent stem cells (hiPSC). We confirmed the presence of a specialized structure between the two cell types that allows neuromodulation and observed that the neuronal stimulation impacts the excitation–contraction coupling properties including the intracellular calcium handling. Finally, we also co-cultivated human neurons (hiPSC-NRs) with human cardiomyocytes (hiPSC-CMs), both obtained from the same hiPSC line. Hence, we have developed a neuro–cardiac compartmentalized in vitro model system that allows us to recapitulate the structural and functional properties of the neuro–cardiac junction and that can also be used to better understand the interaction between the heart and brain in humans, as well as to evaluate the impact of drugs on a reconstructed human neuro–cardiac system. MDPI 2022-11-25 /pmc/articles/PMC9737466/ /pubmed/36497024 http://dx.doi.org/10.3390/cells11233764 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bernardin, Albin A. Colombani, Sarah Rousselot, Antoine Andry, Virginie Goumon, Yannick Delanoë-Ayari, Hélène Pasqualin, Côme Brugg, Bernard Jacotot, Etienne D. Pasquié, Jean-Luc Lacampagne, Alain Meli, Albano C. Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies |
title | Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies |
title_full | Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies |
title_fullStr | Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies |
title_full_unstemmed | Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies |
title_short | Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies |
title_sort | impact of neurons on patient-derived cardiomyocytes using organ-on-a-chip and ipsc biotechnologies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737466/ https://www.ncbi.nlm.nih.gov/pubmed/36497024 http://dx.doi.org/10.3390/cells11233764 |
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