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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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