Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis

Abstract Background Administrating extracellular matrix (ECM) to restore cardiac function post-myocardial infarction (MI) shows promise, however study variability obscures its true impact. We therefore conducted a systematic review and meta-analysis of preclinical studies to assess the effects of EC...

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Main Authors: Atze van der Pol, Marijn C. Peters, Ignasi Jorba, Anke M. Smits, Niels P. van der Kaaij, Marie-Jose Goumans, Kimberley E. Wever, Carlijn V. C. Bouten
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-00812-y
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author Atze van der Pol
Marijn C. Peters
Ignasi Jorba
Anke M. Smits
Niels P. van der Kaaij
Marie-Jose Goumans
Kimberley E. Wever
Carlijn V. C. Bouten
author_facet Atze van der Pol
Marijn C. Peters
Ignasi Jorba
Anke M. Smits
Niels P. van der Kaaij
Marie-Jose Goumans
Kimberley E. Wever
Carlijn V. C. Bouten
author_sort Atze van der Pol
collection DOAJ
description Abstract Background Administrating extracellular matrix (ECM) to restore cardiac function post-myocardial infarction (MI) shows promise, however study variability obscures its true impact. We therefore conducted a systematic review and meta-analysis of preclinical studies to assess the effects of ECM treatments on cardiac function and tissue homeostasis post-MI. Methods We searched PubMed and SCOPUS from inception to June 28, 2024, for animal studies describing ECM treatment post-MI (pre-registered on PROSPERO, CRD42022368400). Random effects meta-analyses compared ECM treatment to controls regarding left ventricular ejection fraction (LVEF), fractional shortening, infarct size, stroke volume, and left ventricular wall thickness. Subgroup analyses examined the influence of sex, species, ECM source, and administration method. Funnel plots and Egger’s regression assessed publication bias. Results We identify 88 articles which meet our inclusion criteria. These studies describe the use of rats (51%), mice (38%), and pigs (11%). 44% of studies use males, 34% females, 5% both sexes, and 17% did not report sex. Most studies employ permanent MI models (85%) over ischemia reperfusion models (15%), and deliver ECM via intramyocardial injection (59%), cardiac patch (39%), cardiac sleeve (1%), or osmotic pump (1%). Our meta-analysis demonstrates that ECM treatment significantly improves LVEF (MD: 10.9%, 95% CI: [8.7%;13.0%]; p = 8.057e-24), fractional shortening (MD: 8.2%, 95% CI: [5.6%; 10.9%]; p = 1.751e-09), stroke volume (SMD 0.6, 95% CI: [0.2;1.0], p = 0.004), left ventricular wall thickening (SMD 1.2, 95% CI: [0.9; 1.5], p = 1.321e-17), while reducing infarct size (-11.7%, 95% CI: [-14.7%;-8.6%], p = 3.699e-14). We find no significant differences between the various subgroups and no indication of publication bias. Conclusions ECM-based treatments significantly enhance cardiac function and tissue homeostasis in preclinical post-MI models, supporting further research toward clinical translation.
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spelling doaj-art-c6c5c477d7b2474b82eadfb6ce96e8a32025-08-20T03:07:44ZengNature PortfolioCommunications Medicine2730-664X2025-03-015111610.1038/s43856-025-00812-yPreclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysisAtze van der Pol0Marijn C. Peters1Ignasi Jorba2Anke M. Smits3Niels P. van der Kaaij4Marie-Jose Goumans5Kimberley E. Wever6Carlijn V. C. Bouten7Soft Tissue Engineering and Mechanobiology, Department of Biomedical Engineering, Eindhoven University of TechnologySoft Tissue Engineering and Mechanobiology, Department of Biomedical Engineering, Eindhoven University of TechnologySoft Tissue Engineering and Mechanobiology, Department of Biomedical Engineering, Eindhoven University of TechnologyDepartment of Cell and Chemical Biology, Leiden University Medical CenterDepartment of Cardiothoracic Surgery, Regenerative Medicine Centre, University Medical Center UtrechtDepartment of Cell and Chemical Biology, Leiden University Medical CenterDepartment of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical CenterSoft Tissue Engineering and Mechanobiology, Department of Biomedical Engineering, Eindhoven University of TechnologyAbstract Background Administrating extracellular matrix (ECM) to restore cardiac function post-myocardial infarction (MI) shows promise, however study variability obscures its true impact. We therefore conducted a systematic review and meta-analysis of preclinical studies to assess the effects of ECM treatments on cardiac function and tissue homeostasis post-MI. Methods We searched PubMed and SCOPUS from inception to June 28, 2024, for animal studies describing ECM treatment post-MI (pre-registered on PROSPERO, CRD42022368400). Random effects meta-analyses compared ECM treatment to controls regarding left ventricular ejection fraction (LVEF), fractional shortening, infarct size, stroke volume, and left ventricular wall thickness. Subgroup analyses examined the influence of sex, species, ECM source, and administration method. Funnel plots and Egger’s regression assessed publication bias. Results We identify 88 articles which meet our inclusion criteria. These studies describe the use of rats (51%), mice (38%), and pigs (11%). 44% of studies use males, 34% females, 5% both sexes, and 17% did not report sex. Most studies employ permanent MI models (85%) over ischemia reperfusion models (15%), and deliver ECM via intramyocardial injection (59%), cardiac patch (39%), cardiac sleeve (1%), or osmotic pump (1%). Our meta-analysis demonstrates that ECM treatment significantly improves LVEF (MD: 10.9%, 95% CI: [8.7%;13.0%]; p = 8.057e-24), fractional shortening (MD: 8.2%, 95% CI: [5.6%; 10.9%]; p = 1.751e-09), stroke volume (SMD 0.6, 95% CI: [0.2;1.0], p = 0.004), left ventricular wall thickening (SMD 1.2, 95% CI: [0.9; 1.5], p = 1.321e-17), while reducing infarct size (-11.7%, 95% CI: [-14.7%;-8.6%], p = 3.699e-14). We find no significant differences between the various subgroups and no indication of publication bias. Conclusions ECM-based treatments significantly enhance cardiac function and tissue homeostasis in preclinical post-MI models, supporting further research toward clinical translation.https://doi.org/10.1038/s43856-025-00812-y
spellingShingle Atze van der Pol
Marijn C. Peters
Ignasi Jorba
Anke M. Smits
Niels P. van der Kaaij
Marie-Jose Goumans
Kimberley E. Wever
Carlijn V. C. Bouten
Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis
Communications Medicine
title Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis
title_full Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis
title_fullStr Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis
title_full_unstemmed Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis
title_short Preclinical extracellular matrix-based treatment strategies for myocardial infarction: a systematic review and meta-analysis
title_sort preclinical extracellular matrix based treatment strategies for myocardial infarction a systematic review and meta analysis
url https://doi.org/10.1038/s43856-025-00812-y
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