演題

IS-1-2

BIOARTIFICIAL HEART: A HUMAN-SIZED PORCINE MODEL- THE WAY AHEAD.

[演者] Alexander Weymann:1
[著者] Nikhil Patil:2, Takayuki Okada:1, Philipp Jungebluth:3, Pal Soos:4, Roland Ishtok:5, Bastian Schmack:1, Matthias Karck:1, Gabor Szabo:1
1:Department of Cardiac Surgery, Heart and Marfan Center - University of Heidelberg, 2:Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Ha, 3:Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, In, 4:Heart and Vascular Center, Semmelweis University, Varosmajor ut 68, H1122 Budapest, Hungary, 5:2nd Department of Pathology, Semmelweis University, Ulloi ut 93, H1091 Budapest, Hungary

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.
詳細検索
アプリバナー iPhone版,iPad版 Android版