(390) - Three-Dimensional Human-Heart Derived Scaffolds

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Heart failure results from damaged myocardium that can severely reduce function and lead to death with very few options for treatment. Recent studies have injected stem cells into the coronary arteries to improve function. Though the potential of stem cell therapy is great, only limited efficacy has been attained, Extracellular matrix (ECM) proteins derived ECM from bowel or bladder and stem cells in concert may have superior benefits to either alone but the homing cues are still limited for engraftment due to lack of organ specific signaling and xenogenic issues. Our goal was to derive a novel three-dimensional human heart extracellular matrix (ECM)-derived scaffold that could serve as a vehicle to deliver cardiac or stem cells directly to the damaged tissue of the heart and remain at the treatment site. Scaffolds were created from purified human heart ECM proteins to expedite clinical translation and actively promote and preserve heart cell phenotype. Scaffolds were imparted with pores 250 um in size to enhance diffusion and cell penetration and distribution. Human cardiomyocytes and cardiac derived-iPSCs were seeded into scaffolds 3 mm in diameter and 0.3 mm thick, cultured and subsequently implanted into NOD-SCID mice. The human cardiomyocytes and cardiac derived iPSCs readily adhered to human cardiac-derived ECM protein scaffolds. Cardiomoycytes within the scaffold maintained representative phenotypes including expression of cardiomyocyte-specific markers and remained electrically active, even beating the scaffold in unison in vitro. In vivo, cardiomyocyte-seeded scaffolds spontaneously adhered to and incorporated with murine infarcted tissue. These results indicate that a novel 3D scaffold made of purified human cardiac ECM can be used as a delivery vehicle for human cardiac cells to directly target damaged heart tissue. Optimization of scaffolds and cell interactions need to be studied further in vivo.