PLoS ONE (Jan 2014)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0111591
Journal volume & issue
Vol. 9, no. 11
p. e111591

Abstract

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BackgroundA 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.MethodsWe 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.ResultsDecellularized 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, pConclusionsHuman-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.