Novel xeno-free human heart matrix-derived three-dimensional scaffolds

Abstract

RationaleMyocardial infarction (MI) results in damaged heart tissue which can progress to severely reduce cardiac function, leading to death. Recent studies have injected dissociated, suspended cardiac cells into coronary arteries to restore function with limited results attributed to poor cell retention and cell death. Extracellular matrix (ECM) injected into damaged cardiac tissue sites show some promising effects. However, combined use of human cardiac ECM and cardiac cells may produce superior benefits to restore cardiac function.ObjectiveThis study was designed to assess use of new three-dimensional human heart ECM-derived scaffolds to serve as vehicles to deliver cardiac-derived cells directly to damaged heart tissue and improve cell retention at these sites while also providing biomechanical support and attracting host cell recruitment.Methods and ResultsECM-derived porous protein scaffolds were fabricated from human heart tissues. These scaffolds were designed to carry, actively promote and preserve cardiac cell phenotype, viability and functional retention in tissue sites. ECM scaffolds were optimized and were seeded with human cardiomyocytes, cultured and subsequently implanted ex vivo onto infarcted murine epicardium. Seeded human cardiomyocytes readily adhered to human cardiac-derived ECM scaffolds and maintained representative phenotypes including expression of cardiomyocyte-specific markers, and remained electrically synchronous within the scaffold in vitro. Ex vivo, cardiomyocyte-seeded ECM scaffolds spontaneously adhered and incorporated into murine ventricle.ConclusionsDecellularized human cardiac tissue-derived 3D ECM scaffolds are effective delivery vehicles for human cardiac cells to directly target ischemic heart tissue and warrant further studies to assess their therapeutic potential in restoring essential cardiac functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0559-0) contains supplementary material, which is available to authorized users.

Prevascularization of Decellularized Porcine Myocardial Slice for Cardiac Tissue Engineering

“…Human heart derived decellularized ECM has enabled the seeding and survival of human cardiomyocytes and maintained representative phenotypes of the seeded cardiomyocytes including expression of cardiomyocyte-specific markers and remained electrically synchronous within the scaffold in vitro. 15 Cardiac patches made of rat decellularized cardiac tissue and induced pluripotent stem cells (iPSCs) derived cardiac cells have been proven to improve heart function in vivo. 16 However, perfusion limitations still exist for cardiac scaffolds derived from decellularized matrix affecting the efficacy and efficiency of their applications.…”

“…Compared with other natural or synthetic scaffolds, decellularized ECM offers many unique advantages such as preserving organ specific microstructure, mechanical properties, and biochemical cues in favor of cell attachment, growth, and tissue specific differentiation. − Decellularized cardiac ECM has also been explored to be used to facilitate cardiac repair. Human heart derived decellularized ECM has enabled the seeding and survival of human cardiomyocytes and maintained representative phenotypes of the seeded cardiomyocytes including expression of cardiomyocyte-specific markers and remained electrically synchronous within the scaffold in vitro . Cardiac patches made of rat decellularized cardiac tissue and induced pluripotent stem cells (iPSCs) derived cardiac cells have been proven to improve heart function in vivo .…”

Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease

“…However, we have performed labeling trials on these cells and genes in a patch for our othe studies. We evaluated only one route of delivery, direct myocardial injection, and not others such as intravenous, endocardial, intracoronary, and/or a patch 70,71 . Some of these would not be feasible in the current mouse model.…”

Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Drug-Induced Inotropic Effects in Early Drug Development. Part 2: Designing and Fabricating Microsystems for Assaying Cardiac Contractility With Physiological Relevance Using Human iPSC-Cardiomyocytes

“…Different studies have also shown that hiPSC-cardiomyocytes can easily attach to a variety of extracellular materials, including Matrigel, fibronectin, laminin, vitronectin, and other extracellular components (Lundy et al, 2013; Burridge et al, 2014; Holt-Casper et al, 2015; Badenes et al, 2016; Ronaldson-Bouchard et al, 2018). This versatility in attaching to different extracellular components also enables the potential of culturing cells in a microenvironment that may recreate a cardiac extracellular matrix (Rienks et al, 2014; Wang et al, 2016; Li et al, 2018).…”