Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury
The cellular and molecular mechanisms that are responsible for the poor regenerative capacity of the adult heart after myocardial infarction (MI) are still unclear and their understanding is crucial to develop novel regenerative therapies. Considering the lack of reliable in vitro tissue-like models...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-10-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314231190147 |
| _version_ | 1797661191377518592 |
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| author | Giulio Ciucci Karim Rahhali Giovanni Cimmino Francesco Natale Paolo Golino Gianfranco Sinagra Chiara Collesi Francesco S Loffredo |
| author_facet | Giulio Ciucci Karim Rahhali Giovanni Cimmino Francesco Natale Paolo Golino Gianfranco Sinagra Chiara Collesi Francesco S Loffredo |
| author_sort | Giulio Ciucci |
| collection | DOAJ |
| description | The cellular and molecular mechanisms that are responsible for the poor regenerative capacity of the adult heart after myocardial infarction (MI) are still unclear and their understanding is crucial to develop novel regenerative therapies. Considering the lack of reliable in vitro tissue-like models to evaluate the molecular mechanisms of cardiac regeneration, we used cryoinjury on rat Engineered Heart Tissues (rEHTs) as a new model which recapitulates in part the in vivo response after myocardial injury of neonatal and adult heart. When we subjected to cryoinjury immature and mature rEHTs, we observed a significant increase in cardiomyocyte (CM) DNA synthesis when compared to the controls. As expected, the number of mitotic CMs significantly increases in immature rEHTs when compared to mature rEHTs, suggesting that the extent of CM maturation plays a crucial role in their proliferative response after cryoinjury. Moreover, we show that cryoinjury induces a temporary activation of fibroblast response in mature EHTs, similar to the early response after MI, that is however incomplete in immature EHTs. Our results support the hypothesis that the endogenous maturation program in cardiac myocytes plays a major role in determining the proliferative response to injury. Therefore, we propose rEHTs as a robust, novel tool to in vitro investigate critical aspects of cardiac regeneration in a tissue-like asset free from confounding factors in response to injury, such as the immune system response or circulating inflammatory cytokines. |
| first_indexed | 2024-03-11T18:41:03Z |
| format | Article |
| id | doaj.art-7290c7500f954497b597d5b0754c1057 |
| institution | Directory Open Access Journal |
| issn | 2041-7314 |
| language | English |
| last_indexed | 2024-03-11T18:41:03Z |
| publishDate | 2023-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj.art-7290c7500f954497b597d5b0754c10572023-10-12T13:04:54ZengSAGE PublishingJournal of Tissue Engineering2041-73142023-10-011410.1177/20417314231190147Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjuryGiulio Ciucci0Karim Rahhali1Giovanni Cimmino2Francesco Natale3Paolo Golino4Gianfranco Sinagra5Chiara Collesi6Francesco S Loffredo7Molecular Cardiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Friuli-Venezia Giulia, ItalyMolecular Medicine, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyDepartment of Translational Medical Sciences, Division of Cardiology, University of Campania “L. Vanvitelli,” Naples, ItalyDepartment of Translational Medical Sciences, Division of Cardiology, University of Campania “L. Vanvitelli,” Naples, ItalyDepartment of Translational Medical Sciences, Division of Cardiology, University of Campania “L. Vanvitelli,” Naples, ItalyDepartment of Medicine, Surgery and Health Sciences, Azienda Sanitaria-Universitaria Integrata Trieste “ASUITS,” University of Trieste, Trieste, ItalyMolecular Medicine, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyDepartment of Translational Medical Sciences, Division of Cardiology, University of Campania “L. Vanvitelli,” Naples, ItalyThe cellular and molecular mechanisms that are responsible for the poor regenerative capacity of the adult heart after myocardial infarction (MI) are still unclear and their understanding is crucial to develop novel regenerative therapies. Considering the lack of reliable in vitro tissue-like models to evaluate the molecular mechanisms of cardiac regeneration, we used cryoinjury on rat Engineered Heart Tissues (rEHTs) as a new model which recapitulates in part the in vivo response after myocardial injury of neonatal and adult heart. When we subjected to cryoinjury immature and mature rEHTs, we observed a significant increase in cardiomyocyte (CM) DNA synthesis when compared to the controls. As expected, the number of mitotic CMs significantly increases in immature rEHTs when compared to mature rEHTs, suggesting that the extent of CM maturation plays a crucial role in their proliferative response after cryoinjury. Moreover, we show that cryoinjury induces a temporary activation of fibroblast response in mature EHTs, similar to the early response after MI, that is however incomplete in immature EHTs. Our results support the hypothesis that the endogenous maturation program in cardiac myocytes plays a major role in determining the proliferative response to injury. Therefore, we propose rEHTs as a robust, novel tool to in vitro investigate critical aspects of cardiac regeneration in a tissue-like asset free from confounding factors in response to injury, such as the immune system response or circulating inflammatory cytokines.https://doi.org/10.1177/20417314231190147 |
| spellingShingle | Giulio Ciucci Karim Rahhali Giovanni Cimmino Francesco Natale Paolo Golino Gianfranco Sinagra Chiara Collesi Francesco S Loffredo Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury Journal of Tissue Engineering |
| title | Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury |
| title_full | Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury |
| title_fullStr | Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury |
| title_full_unstemmed | Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury |
| title_short | Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury |
| title_sort | engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury |
| url | https://doi.org/10.1177/20417314231190147 |
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