Bioartificial Heart: a Human-sized Porcine Model--the Way Ahead

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Nov 4

PMID 25365554

Citations 33

Authors

Alexander Weymann

Nikhil Prakash Patil

Anton Sabashnikov

Philipp Jungebluth

Sevil Korkmaz

Shiliang Li

Gabor Veres

Pal Soos

Roland Ishtok

Nicole Chaimow

Ines Patzold

Natalie Czerny

Carsten Schies

Bastian Schmack

Aron-Frederik Popov

Andre Rudiger Simon

Matthias Karck

Gabor Szabo

Affiliations

Soon will be listed here.

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.

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