oa Regenerating the human heart: proof of principle to patient-derived myocardial tissue

In the United States, nearly six million people currently suffer from heart failure. Organ transplantation remains the only definitive treatment for end-organ failure. However, the supply of donor organs is limited. Lifelong immunosuppression and chronic rejection limit widespread clinical impact of organ transplantation. The creation of an autologous bioartificial heart with preserved coronary and three-dimensional architecture could theoretically bypass these issues by providing a source of donor organs. Anterograde coronary perfusion of detergents (Sodium Dodecyl Sulfate: SDS, De-ionized water, and Triton-X) produced acellular heart scaffolds from small (rats) and human-sized (porcine and human) hearts. Perfusion-decellularized hearts were void of cellular content (DNA) and perfusing detergents (SDS) but had preserved coronary anatomy and gross structural integrity (sGAG quantification; immunohistochemistry for matrix proteins Collagen I, III, IV, X, Laminin, Fibronectin, Elastin).

Perfusion-decellularized whole heart scaffolds are biocompatible (ability to act as a substrate to support the appropriate cellular activity) when repopulated with neonatal rat cardiomyocytes1 or human induced-pluripotent stem cells (hiPSCs) as evident by cellular attachment and expansion. When seeded onto perfusion-decellularized heart scaffold slices, hiPSCs-derived cardiomyocytes form functional myocardial tissue, in vitro (visible spontaneous beating; immunofluorescence for myosin heavy chain and connexin-43).