Chein’s group isolated progenitors that could ultimately be used to create 3D viable cell constructs that could regenerate a single portion of a damaged heart. also used cell sheets, but found a multilayer construct with increased ECM content provides better efficacy. The Okano group pioneered beating contiguous cardiomyocyte cell sheets for use as heart patches and demonstrated their utility in porcine and rat models. Notably, cell delivery modalities include gel-based injectable cell-containing carriers and living cell sheets to retain cells at the injured site. This pathology plus the long-standing inability to retain sufficient amounts of injected cells in MI tissue sites has prompted increasing use of biomaterials-based approaches to such cardiac tissue cellular therapeutic strategies. These limitations must be addressed to increase treatment efficacy.Īutologous human myoskeletal cell suspensions injected into human cardiac MI sites have produced spontaneous arrhythmias. The majority of cells are lost to filter organs such as the liver and spleen. Furthermore, cells delivered through systemic circulation or coronary arteries have low rates of localization to the infarcted myocardium, and it has been reported that only 10–15% of transepicardially injected cells are retained in the myocardium. Additionally, cells injected after MI encounter a harsh environment that promotes apoptosis, and the majority of injected cells die within 4 days. However, cell survival, engraftment, and control of cell differentiation state are major challenges associated with the local injection of cell populations for heart repair. Clinical trial data has shown a reduction in myocardial scarring, a degree of healthy myocardial regeneration, or an increase in left ventricular ejection fraction in response to post-infarction cell therapy. Towards this end, cell therapy strategies-including stem cell delivery-are now actively developed, with some showing promising results for restoring cardiac function. Due to limited intrinsic repair potential exhibited by the heart, much research has been directed towards improved methods for cardiac tissue regeneration. Furthermore, the resulting necrotic tissue acute zone is typically replaced by dense fibrous scar, impeding cardiac tissue regeneration and restoration of normal heart function. During MI, blood flow to a section of the heart is cut off, subsequently contributing to local acute tissue ischemia and the death of approximately one billion cardiomyocytes. Yearly, ~525,000 Americans will experience their first myocardial infarction (MI) and 190,000 will have a recurrent attack. Ischemic heart disease is currently the leading cause of death in the United States. Conclusionsĭecellularized 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. Ex vivo, cardiomyocyte-seeded ECM scaffolds spontaneously adhered and incorporated into murine ventricle. 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. ECM scaffolds were optimized and were seeded with human cardiomyocytes, cultured and subsequently implanted ex vivo onto infarcted murine epicardium. These scaffolds were designed to carry, actively promote and preserve cardiac cell phenotype, viability and functional retention in tissue sites. Methods and ResultsĮCM-derived porous protein scaffolds were fabricated from human heart tissues. This 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. However, combined use of human cardiac ECM and cardiac cells may produce superior benefits to restore cardiac function. Extracellular matrix (ECM) injected into damaged cardiac tissue sites show some promising effects. 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. Myocardial infarction (MI) results in damaged heart tissue which can progress to severely reduce cardiac function, leading to death.
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