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PLoS One. 2014 Nov 3;9(11):e111591. doi: 10.1371/journal.pone.0111591. eCollection 2014.

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

Author information

1
Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, Heidelberg, Germany.
2
Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, United Kingdom.
3
Department of Clinical Science, Intervention and Technology, Advanced Center for Translational Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
4
Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
5
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.

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.

PMID:
25365554
PMCID:
PMC4218780
DOI:
10.1371/journal.pone.0111591
[Indexed for MEDLINE]
Free PMC Article

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