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

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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.

Original languageEnglish
Article numbere111591
JournalPloS one
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 3 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Weymann, A., Patil, N. P., Sabashnikov, A., Jungebluth, P., Korkmaz, S., Li, S., Veres, G., Soos, P., Ishtok, R., Chaimow, N., Pätzold, I., Czerny, N., Schies, C., Schmack, B., Popov, A. F., Simon, A. R., Karck, M., & Szabo, G. (2014). Bioartificial heart: A human-sized porcine model - The way ahead. PloS one, 9(11), [e111591]. https://doi.org/10.1371/journal.pone.0111591