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.
Highlights
Ischemic heart disease is currently the leading cause of death in the United States
Extracellular matrix (ECM)-derived porous protein scaffolds were fabricated from human heart tissues
Decellularized 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
Summary
Ischemic heart disease is currently the leading cause of death in the United States. Yearly, ~525,000 Americans will experience their first myocardial infarction (MI) and 190,000 will have a recurrent attack [1]. Holt‐Casper et al J Transl Med (2015) 13:194 differentiation state are major challenges associated with the local injection of cell populations for heart repair [8]. Cells delivered through systemic circulation or coronary arteries have low rates of localization to the infarcted myocardium [9, 10], and it has been reported that only 10–15% of transepicardially injected cells are retained in the myocardium [11]. The majority of cells are lost to filter organs such as the liver and spleen [12]. These limitations must be addressed to increase treatment efficacy
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