Bioartificial heart: a human-sized porcine model--the way ahead.
Bioartificial heart: a human-sized porcine model--the way ahead.
复制标题
DOI：
10.1371/journal.pone.0111591
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Szabo G
中科院分区：
文献类型：
--
作者：
Weymann A;Patil NP;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 AF;Simon AR;Karck M;Szabo G
生物人工心脏是一种理论上的替代移植或机械左心室支持。原生心脏脱细胞，保留了结构和血管系统，可为器官再生提供脱细胞组织平台。我们试图在人类大小的猪心脏中开发一种组织工程的全心脏新支架。我们在改良的Langendorff电路中用离子清洁剂冠脉灌注去除猪心脏（n = 10）的细胞。我们通过组织学、透射电子显微镜和荧光显微镜证实了脱细胞现象，通过分光光度法定量了残留DNA，并通过离体左心室压力/容积研究评估了生物力学稳定性，所有这些都与对照组进行了比较。然后，我们将脱细胞的猪心脏放置在生物反应器中，并在模拟的生理条件下将其与小鼠新生儿心脏细胞和人脐带内皮细胞（HUVEC）重新植入。去细胞心脏缺乏细胞内成分，但保留了特定的胶原纤维、蛋白聚糖、弹性蛋白和机械完整性；定量DNA分析显示，与对照组相比，DNA显著减少（82.6±3.2 ng DNA/mg组织vs. 473.2±13.4 ng DNA/mg组织，p<0.05）。再细胞化的猪全心新支架在10天后显示冠状血管的再内皮化和可测量的内在心肌电活动，灌注器官培养维持长达3周。人类大小的脱细胞猪心脏提供了一个有前途的组织工程平台，可能导致未来治疗心力衰竭的临床策略。
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. 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. 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. Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.
登录
查看更多内容
影响因子：
3.1
作者：
Hara, Hidetaka;Long, Cassandra;Cooper, David K. C.
通讯作者：
Cooper, David K. C.
影响因子：
3.8
作者：
Gopalan, SM;Flaim, C;McCulloch, AD
通讯作者：
McCulloch, AD
影响因子：
20.1
作者：
Zimmermann, WH;Schneiderbanger, K;Eschenhagen, T
通讯作者：
Eschenhagen, T
影响因子：
37.8
作者：
Robinson, KA;Li, JS;Badylak, SF
通讯作者：
Badylak, SF
影响因子：
3.3
作者：
Weymann, Alexander;Loganathan, Sivakkanan;Szabo, Gabor
通讯作者：
Szabo, Gabor