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. 2015 Aug:61:279-89.
doi: 10.1016/j.biomaterials.2015.04.056. Epub 2015 May 13.

Acellular human heart matrix: A critical step toward whole heart grafts

Pedro L Sánchez  1 , M Eugenia Fernández-Santos  2 , Salvatore Costanza  3 , Andreu M Climent  4 , Isabel Moscoso  5 , M Angeles Gonzalez-Nicolas  4 , Ricardo Sanz-Ruiz  6 , Hugo Rodríguez  7 , Stefan M Kren  8 , Gregorio Garrido  9 , Jose L Escalante  10 , Javier Bermejo  11 , Jaime Elizaga  11 , Javier Menarguez  12 , Raquel Yotti  11 , Candelas Pérez del Villar  11 , M Angeles Espinosa  6 , María S Guillem  4 , James T Willerson  13 , Antonio Bernad  5 , Rafael Matesanz  9 , Doris A Taylor  14 , Francisco Fernández-Avilés  15
Affiliations

Acellular human heart matrix: A critical step toward whole heart grafts

Pedro L Sánchez et al. Biomaterials. 2015 Aug.

Abstract

The best definitive treatment option for end-stage heart failure currently is transplantation, which is limited by donor availability and immunorejection. Generating an autologous bioartificial heart could overcome these limitations. Here, we have decellularized a human heart, preserving its 3-dimensional architecture and vascularity, and recellularized the decellularized extracellular matrix (dECM). We decellularized 39 human hearts with sodium-dodecyl-sulfate for 4-8 days. Cell removal and architectural integrity were determined anatomically, functionally, and histologically. To assess cytocompatibility, we cultured human cardiac-progenitor cells (hCPC), bone-marrow mesenchymal cells (hMSCs), human endothelial cells (HUVECs), and H9c1 and HL-1 cardiomyocytes in vitro on dECM ventricles up to 21 days. Cell survival, gene expression, organization and/or electrical coupling were analyzed and compared to conventional 2-dimensional cultures. Decellularization removed cells but preserved the 3-dimensional cardiac macro and microstructure and the native vascular network in a perfusable state. Cell survival was observed on dECM for 21 days. hCPCs and hMSCs expressed cardiocyte genes but did not adopt cardiocyte morphology or organization; HUVECs formed a lining of endocardium and vasculature; differentiated cardiomyocytes organized into nascent muscle bundles and displayed mature calcium dynamics and electrical coupling in recellularized dECM. In summary, decellularization of human hearts provides a biocompatible scaffold that retains 3-dimensional architecture and vascularity and that can be recellularized with parenchymal and vascular cells. dECM promotes cardiocyte gene expression in stem cells and organizes existing cardiomyocytes into nascent muscle showing electrical coupling. These findings represent a first step toward manufacturing human heart grafts or matrix components for treating cardiovascular disease.

Keywords: Cardiovascular diseases; Cells; Myocardium; Tissue.

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