Abstract
BackgroundA 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.MethodsWe 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.ResultsDecellularized 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.ConclusionsHuman-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.
Highlights
Heart transplantation is the definitive treatment for end-stage heart failure, but is limited by donor organ shortage and waitinglist mortality
If whole hearts can be decellularized while preserving 3D geometry and vasculature, the resulting scaffold may provide an architectural skeleton for whole-organ tissue engineering
The cardiac cells were removed from the hearts, but collagen types I and III remained, with preserved fiber composition and orientation of the myocardial extracellular matrix components (ECM) (Figure 3 A-H)
Summary
Heart transplantation is the definitive treatment for end-stage heart failure, but is limited by donor organ shortage and waitinglist mortality. Whereas mechanical circulatory support mandates anticoagulation with its inherent risks, heart transplant recipients must live with the ‘‘necessary evil’’ of lifelong immunosuppression and invasive surveillance studies, often begetting hypertension, diabetes, renal failure, malignancy and other sequelae of chronic immunosuppression [1,2]. If whole hearts can be decellularized while preserving 3D geometry and vasculature, the resulting scaffold may provide an architectural skeleton for whole-organ tissue engineering. Due to the density, mass, and 3D architecture of most whole organs such as the heart, liver, and kidney, traditional decellularization methods like immersionagitation are ineffective at removing cellular material [3]. 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
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