Bioartificial heart: a human-sized porcine model--the way ahead.
<h4>Background</h4>A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop...
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2014
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oai:doaj.org-article:36718c18f9bb4aa4a1b9c3aed15297512021-11-25T05:54:46ZBioartificial heart: a human-sized porcine model--the way ahead.1932-620310.1371/journal.pone.0111591https://doaj.org/article/36718c18f9bb4aa4a1b9c3aed15297512014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0111591https://doaj.org/toc/1932-6203<h4>Background</h4>A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts.<h4>Methods</h4>We decellularized porcine hearts (n = 10) by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC) under simulated physiological conditions.<h4>Results</h4>Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05). Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks.<h4>Conclusions</h4>Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.Alexander WeymannNikhil Prakash PatilAnton SabashnikovPhilipp JungebluthSevil KorkmazShiliang LiGabor VeresPal SoosRoland IshtokNicole ChaimowInes PätzoldNatalie CzernyCarsten SchiesBastian SchmackAron-Frederik PopovAndré Rüdiger SimonMatthias KarckGabor SzaboPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 11, p e111591 (2014) |
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Medicine R Science Q Alexander Weymann Nikhil Prakash Patil Anton Sabashnikov Philipp Jungebluth Sevil Korkmaz Shiliang Li Gabor Veres Pal Soos Roland Ishtok Nicole Chaimow Ines Pätzold Natalie Czerny Carsten Schies Bastian Schmack Aron-Frederik Popov André Rüdiger Simon Matthias Karck Gabor Szabo Bioartificial heart: a human-sized porcine model--the way ahead. |
| description |
<h4>Background</h4>A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts.<h4>Methods</h4>We decellularized porcine hearts (n = 10) by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC) under simulated physiological conditions.<h4>Results</h4>Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05). Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks.<h4>Conclusions</h4>Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure. |
| format |
article |
| author |
Alexander Weymann Nikhil Prakash Patil Anton Sabashnikov Philipp Jungebluth Sevil Korkmaz Shiliang Li Gabor Veres Pal Soos Roland Ishtok Nicole Chaimow Ines Pätzold Natalie Czerny Carsten Schies Bastian Schmack Aron-Frederik Popov André Rüdiger Simon Matthias Karck Gabor Szabo |
| author_facet |
Alexander Weymann Nikhil Prakash Patil Anton Sabashnikov Philipp Jungebluth Sevil Korkmaz Shiliang Li Gabor Veres Pal Soos Roland Ishtok Nicole Chaimow Ines Pätzold Natalie Czerny Carsten Schies Bastian Schmack Aron-Frederik Popov André Rüdiger Simon Matthias Karck Gabor Szabo |
| author_sort |
Alexander Weymann |
| title |
Bioartificial heart: a human-sized porcine model--the way ahead. |
| title_short |
Bioartificial heart: a human-sized porcine model--the way ahead. |
| title_full |
Bioartificial heart: a human-sized porcine model--the way ahead. |
| title_fullStr |
Bioartificial heart: a human-sized porcine model--the way ahead. |
| title_full_unstemmed |
Bioartificial heart: a human-sized porcine model--the way ahead. |
| title_sort |
bioartificial heart: a human-sized porcine model--the way ahead. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/36718c18f9bb4aa4a1b9c3aed1529751 |
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