Virginia B. Neese
Introduction: Myocardial infarction (MI) remains the leading cause of mortality and morbidity in developed countries1. MIs account for up to 700,000 deaths annually in the United States2. Current management focuses on revascularization to prevent further damage, but no therapies are currently approved for restoring loss function or for replacing dead cardiomyocytes1,3. Cardiomyocytes have a limited ability to regenerate and as such, stem cells offer a promising solution because of their ability to replicate and differentiate. However, current delivery systems have been unable to produce significant cell survival, myocyte differentiating or engraftment after transplantation. Decellularized extracellular matrices (ECM) coated with cardiomyocyte induced mesenchymal stem cells hold great promise for addressing these limitations1,4. Methods: Acellular scaffolds from cadaveric pig hearts were coated with decellularized heart ECM. These scaffolds were re-endothelialized using both a venous and an arterial approach5. Results: Re-endothelialized vessels were found to produce endothelial nitrous oxide and von Willerbrand factor. Correspondingly, there was a decrease in thrombogenecity (P<0.05). In addition, the re-endothelialized scaffolds produced cardiomyocytes with improved contractility compared to control acellular scaffolds in rats5. Conclusion: Decellularized heart ECM scaffolds increase cell survival and differentiation by providing environmental factors and structure resembling that of a pre-ischemic heart. As such, they may offer the best solution for introducing induced stem cells into damaged myocardium following a MI. A phase 1 study is currently underway in the United States to determine the safety and feasibility of a hydrogel (VentriGel) of decellularized pig ECM for therapeutic use in patients suffering from post-MI ventricular dysfunction4.
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