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Bioartificial heart: a human-sized porcine model : the way ahead

Background: 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...

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Main Authors: Weymann, Alexander (Author) , Korkmaz-İçöz, Sevil (Author) , Li, Shiliang (Author) , Veres, Gábor (Author) , Chaimow, Nicole (Author) , Pätzold, Ines (Author) , Czerny, Natalie (Author) , Schies, Carsten (Author) , Schmack, Bastian (Author) , Karck, Matthias (Author) , Szabó, Gábor (Author)
Format: Article (Journal)
Language:English
Published: November 3, 2014
In: PLOS ONE
Year: 2014, Volume: 9, Issue: 11
ISSN:1932-6203
DOI:10.1371/journal.pone.0111591
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0111591
Verlag, lizenzpflichtig, Volltext: https://dx.plos.org/10.1371/journal.pone.0111591
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Author Notes: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
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Summary:Background: 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. - Methods: 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. - Results: 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 (82.663.2 ng DNA/mg tissue vs. 473.2613.4 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. - Conclusions: Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.
Item Description:Gesehen am 18.08.2020
Physical Description:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0111591

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