Acellular bioscaffolds redirect cardiac fibroblasts and promote functional tissue repair in rodents and humans with myocardial injury
| Autor: | Darrell D. Belke, Samar Tarraf, Holly E Mewhort, David G. Guzzardi, James A. White, Sean Kang, Ali Fatehi Hassanabad, Guoqi Teng, Karl T. Wagner, Paul W.M. Fedak, Bobak Heydari, Matthew Cheung, Jeannine D. Turnbull, Yoko Mikami, D.A. Svystonyuk, Elena S. DiMartino, Jacqueline Flewitt |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Myocardial Infarction lcsh:Medicine Rodentia Heart failure 030204 cardiovascular system & hematology Article Cell Line Extracellular matrix Cohort Studies 03 medical and health sciences Paracrine signalling Cicatrix 0302 clinical medicine Vasculogenesis Downregulation and upregulation Fibrosis medicine Animals Humans Tissue engineering Myocardial infarction lcsh:Science Multidisciplinary Tissue Scaffolds Ventricular Remodeling business.industry Myocardium lcsh:R Heart Fibroblasts Translational research medicine.disease Extracellular Matrix Rats 030104 developmental biology Heart Injuries Cell culture lcsh:Q Cardiac regeneration business Perfusion |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-17 (2020) |
| ISSN: | 2045-2322 |
| Popis: | Coronary heart disease is a leading cause of death. Tissue remodeling and fibrosis results in cardiac pump dysfunction and ischemic heart failure. Cardiac fibroblasts may rebuild damaged tissues when prompted by suitable environmental cues. Here, we use acellular biologic extracellular matrix scaffolds (bioscaffolds) to stimulate pathways of muscle repair and restore tissue function. We show that acellular bioscaffolds with bioinductive properties can redirect cardiac fibroblasts to rebuild microvascular networks and avoid tissue fibrosis. Specifically, when human cardiac fibroblasts are combined with bioactive scaffolds, gene expression is upregulated and paracrine mediators are released that promote vasculogenesis and prevent scarring. We assess these properties in rodents with myocardial infarction and observe bioscaffolds to redirect fibroblasts, reduce tissue fibrosis and prevent maladaptive structural remodeling. Our preclinical data confirms that acellular bioscaffold therapy provides an appropriate microenvironment to stimulate pathways of functional repair. We translate our observations to patients with coronary heart disease by conducting a first-in-human observational cohort study. We show that bioscaffold therapy is associated with improved perfusion of infarcted myocardium, reduced myocardial scar burden, and reverse structural remodeling. We establish that clinical use of acellular bioscaffolds is feasible and offers a new frontier to enhance surgical revascularization of ischemic heart muscle. |
| Databáze: | OpenAIRE |
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