Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair
Structural cardiac remodeling after ischemic injury can induce a transition to heart failure from progressive loss of cardiac function. Cellular regenerative therapies are promising but face significant translational hurdles. Tissue extracellular matrix (ECM) holds the necessary environmental cues t...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | JACC: Basic to Translational Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X17301389 |
| _version_ | 1818111155022856192 |
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| author | Holly E.M. Mewhort, MD, PhD Daniyil A. Svystonyuk, BSc Jeannine D. Turnbull, BSc Guoqi Teng, PhD Darrell D. Belke, PhD David G. Guzzardi, BSc Daniel S. Park, BSc Sean Kang, BSc Morley D. Hollenberg, MD, PhD Paul W.M. Fedak, MD, PhD |
| author_facet | Holly E.M. Mewhort, MD, PhD Daniyil A. Svystonyuk, BSc Jeannine D. Turnbull, BSc Guoqi Teng, PhD Darrell D. Belke, PhD David G. Guzzardi, BSc Daniel S. Park, BSc Sean Kang, BSc Morley D. Hollenberg, MD, PhD Paul W.M. Fedak, MD, PhD |
| author_sort | Holly E.M. Mewhort, MD, PhD |
| collection | DOAJ |
| description | Structural cardiac remodeling after ischemic injury can induce a transition to heart failure from progressive loss of cardiac function. Cellular regenerative therapies are promising but face significant translational hurdles. Tissue extracellular matrix (ECM) holds the necessary environmental cues to stimulate cell-based endogenous myocardial repair pathways and promote adaptive remodeling toward functional recovery. Heart epicardium has emerged as an important anatomic niche for endogenous repair pathways including vasculogenesis and cardiogenesis. We show that acellular ECM scaffolds surgically implanted on the epicardium following myocardial infarction (MI) can attenuate structural cardiac remodeling and improve functional recovery. We assessed the efficacy of this strategy on post-MI functional recovery by comparing intact bioactive scaffolds with biologically inactivated ECM scaffolds. We confirm that bioactive properties within the acellular ECM biomaterial are essential for the observed functional benefits. We show that interaction of human cardiac fibroblasts with bioactive ECM can induce a robust cell-mediated vasculogenic paracrine response capable of functional blood vessel assembly. Fibroblast growth factor-2 is uncovered as a critical regulator of this novel bioinductive effect. Acellular bioactive ECM scaffolds surgically implanted on the epicardium post-MI can reprogram resident fibroblasts and stimulate adaptive pro-reparative pathways enhancing functional recovery. We introduce a novel surgical strategy for tissue repair that can be performed as an adjunct to conventional surgical revascularization with minimal translational challenges. |
| first_indexed | 2024-12-11T02:58:32Z |
| format | Article |
| id | doaj.art-cf90dedf8ce14b09a6a5fae040d08d80 |
| institution | Directory Open Access Journal |
| issn | 2452-302X |
| language | English |
| last_indexed | 2024-12-11T02:58:32Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Basic to Translational Science |
| spelling | doaj.art-cf90dedf8ce14b09a6a5fae040d08d802022-12-22T01:23:05ZengElsevierJACC: Basic to Translational Science2452-302X2017-08-012445046410.1016/j.jacbts.2017.05.005Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and RepairHolly E.M. Mewhort, MD, PhD0Daniyil A. Svystonyuk, BSc1Jeannine D. Turnbull, BSc2Guoqi Teng, PhD3Darrell D. Belke, PhD4David G. Guzzardi, BSc5Daniel S. Park, BSc6Sean Kang, BSc7Morley D. Hollenberg, MD, PhD8Paul W.M. Fedak, MD, PhD9Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaDepartment of Physiology and Pharmacology, Department of Medicine, Cumming School of Medicine, Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, CanadaSection of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, CanadaStructural cardiac remodeling after ischemic injury can induce a transition to heart failure from progressive loss of cardiac function. Cellular regenerative therapies are promising but face significant translational hurdles. Tissue extracellular matrix (ECM) holds the necessary environmental cues to stimulate cell-based endogenous myocardial repair pathways and promote adaptive remodeling toward functional recovery. Heart epicardium has emerged as an important anatomic niche for endogenous repair pathways including vasculogenesis and cardiogenesis. We show that acellular ECM scaffolds surgically implanted on the epicardium following myocardial infarction (MI) can attenuate structural cardiac remodeling and improve functional recovery. We assessed the efficacy of this strategy on post-MI functional recovery by comparing intact bioactive scaffolds with biologically inactivated ECM scaffolds. We confirm that bioactive properties within the acellular ECM biomaterial are essential for the observed functional benefits. We show that interaction of human cardiac fibroblasts with bioactive ECM can induce a robust cell-mediated vasculogenic paracrine response capable of functional blood vessel assembly. Fibroblast growth factor-2 is uncovered as a critical regulator of this novel bioinductive effect. Acellular bioactive ECM scaffolds surgically implanted on the epicardium post-MI can reprogram resident fibroblasts and stimulate adaptive pro-reparative pathways enhancing functional recovery. We introduce a novel surgical strategy for tissue repair that can be performed as an adjunct to conventional surgical revascularization with minimal translational challenges.http://www.sciencedirect.com/science/article/pii/S2452302X17301389extracellular matrixregenerationvasculogenesis |
| spellingShingle | Holly E.M. Mewhort, MD, PhD Daniyil A. Svystonyuk, BSc Jeannine D. Turnbull, BSc Guoqi Teng, PhD Darrell D. Belke, PhD David G. Guzzardi, BSc Daniel S. Park, BSc Sean Kang, BSc Morley D. Hollenberg, MD, PhD Paul W.M. Fedak, MD, PhD Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair JACC: Basic to Translational Science extracellular matrix regeneration vasculogenesis |
| title | Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair |
| title_full | Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair |
| title_fullStr | Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair |
| title_full_unstemmed | Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair |
| title_short | Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair |
| title_sort | bioactive extracellular matrix scaffold promotes adaptive cardiac remodeling and repair |
| topic | extracellular matrix regeneration vasculogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2452302X17301389 |
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