Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.
The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic c...
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doaj-15877dea233746538ab5a361b1a6c2082020-11-25T01:01:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011111e016696310.1371/journal.pone.0166963Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.Daniel BiermannAlexandra EderFlorian ArndtHatim SeoudyHermann ReichenspurnerThomas MirArlindo RisoRainer Kozlik-FeldmannKersten PeldschusMichael G KaulTillman SchulerSusanne KrasemannArne HansenThomas EschenhagenJörg S SachwehThe long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.http://europepmc.org/articles/PMC5119816?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel Biermann Alexandra Eder Florian Arndt Hatim Seoudy Hermann Reichenspurner Thomas Mir Arlindo Riso Rainer Kozlik-Feldmann Kersten Peldschus Michael G Kaul Tillman Schuler Susanne Krasemann Arne Hansen Thomas Eschenhagen Jörg S Sachweh |
spellingShingle |
Daniel Biermann Alexandra Eder Florian Arndt Hatim Seoudy Hermann Reichenspurner Thomas Mir Arlindo Riso Rainer Kozlik-Feldmann Kersten Peldschus Michael G Kaul Tillman Schuler Susanne Krasemann Arne Hansen Thomas Eschenhagen Jörg S Sachweh Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation. PLoS ONE |
author_facet |
Daniel Biermann Alexandra Eder Florian Arndt Hatim Seoudy Hermann Reichenspurner Thomas Mir Arlindo Riso Rainer Kozlik-Feldmann Kersten Peldschus Michael G Kaul Tillman Schuler Susanne Krasemann Arne Hansen Thomas Eschenhagen Jörg S Sachweh |
author_sort |
Daniel Biermann |
title |
Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation. |
title_short |
Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation. |
title_full |
Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation. |
title_fullStr |
Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation. |
title_full_unstemmed |
Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation. |
title_sort |
towards a tissue-engineered contractile fontan-conduit: the fate of cardiac myocytes in the subpulmonary circulation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit. |
url |
http://europepmc.org/articles/PMC5119816?pdf=render |
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