title: Bioartificial heart: a human-sized porcine model--the way ahead.
abstract: 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 (82.6±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.
  
  
  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.
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Weymann
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, United Kingdom.
authors.forename: Nikhil Prakash
authors.initials: NP
authors.lastname: Patil
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, United Kingdom.
authors.forename: Anton
authors.initials: A
authors.lastname: Sabashnikov
authors.affiliation: Department of Clinical Science, Intervention and Technology, Advanced Center for Translational Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jungebluth
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Sevil
authors.initials: S
authors.lastname: Korkmaz
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.affiliation: Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Pal
authors.initials: P
authors.lastname: Soos
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Roland
authors.initials: R
authors.lastname: Ishtok
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Chaimow
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Pätzold
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Czerny
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schies
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schmack
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, United Kingdom.
authors.forename: Aron-Frederik
authors.initials: AF
authors.lastname: Popov
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, United Kingdom.
authors.forename: André Rüdiger
authors.initials: AR
authors.lastname: Simon
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.affiliation: Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
authors.forename: Gabor
authors.initials: G
authors.lastname: Szabo
mesh_terms: D000818:Animals; D005260:Female; D048091:Guided Tissue Regeneration / Q000379:methods*; D006354:Heart, Artificial; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000166:cytology; D013552:Swine; D023822:Tissue Engineering; D054457:Tissue Scaffolds