Abstract

Cardiac tissue engineering using biomaterials with or without a combination of cardiac stem cell therapy offers a new therapeutic option for repairing infarcted heart. So far, cardiac tissue scaffold is designed mainly based on natural and synthetic biomaterials, which do not mimic human myocardial extracellular matrix. This raises a fundamental issue about the biocompatibility of currently used biomaterials with myocardial tissue. Here we hypothesized that human heart valve-derived scaffold (hHVS) may provide a clinically relevant novel biomaterial for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function, as shown by transthoracic echocardiography as well as by hemodynamic measurements via a Millar catheter, and by reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first evidence for translating the hHVS-based cardiac tissue engineering into clinical strategies to treat myocardial infarction.

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