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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Clinical and Translational Cardiovascular Medicine
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1427023
This article is part of the Research Topic Translational Advances in Cardiovascular Therapy: From Bench to Bedside View all articles

Intra-myocardial immunomodulation with human CD16 + monocytes to treat myocardial infarction in pig: a blind randomized preclinical trial

Provisionally accepted
Raimondo Ascione Raimondo Ascione 1*Vito D. Bruno Vito D. Bruno 1Tom Johnson Tom Johnson 1Eva Sammut Eva Sammut 1Andrew Bond Andrew Bond 1Daniel Lopez-Baz Daniel Lopez-Baz 1Julia Deutsch Julia Deutsch 1Michael Bailey Michael Bailey 1Amedeo Chiribiri Amedeo Chiribiri 2Ashish Patel Ashish Patel 2Andy H. Baker Andy H. Baker 3Bijan Modarai Bijan Modarai 2
  • 1 University of Bristol, Bristol, United Kingdom
  • 2 King's College London, London, England, United Kingdom
  • 3 University of Edinburgh, Edinburgh, Scotland, United Kingdom

The final, formatted version of the article will be published soon.

    Human CD16 + monocytes (hCD16 + Ms) have pro-angiogenic properties. We assessed the feasibility, safety and efficacy of hCD16 + Ms in a porcine model of myocardial infarction (MI).27 female Large-White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR).Five days later animals received intramyocardial injections of hCD16 + Ms in saline (n=13) or saline only (n=14). hCD16 + Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87% respectively. No feasibility/safety concerns were associated with the use of hCD16 + Ms. The LV scar dropped by 14.5gr (from 25.45±8.24 to 10.8±3.4 gr; -55%) and by 6.4gr (from 18.83±5.06 to 12.4±3.9gr; -30%) in the hCD16 + Ms and control groups respectively (p=0.015). 30-day LVEF did not differ between groups, but a pre-specified sub-analysis within the hCD16 + Ms group showed that LVEF was 2.8% higher and LV scar 2.9gr lower in the subgroup receiving higher celldose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6, and lower levels of TGF-β were observed in the hCD16 + Ms group.The use of hCD16 + Ms in acute MI is feasible, safe and is associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts, IL-6 and reduced pro-fibrotic TGF-β at 30-day postinjections. A higher cell-dose might increase LVEF effect while reducing scar size, but this warrants validation in future studies.

    Keywords: Myocardial Infarction, Ischemic heart failure, Treatment, Immunomodulation, Monocytes, Intramyocardial delivery

    Received: 02 May 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Ascione, Bruno, Johnson, Sammut, Bond, Lopez-Baz, Deutsch, Bailey, Chiribiri, Patel, Baker and Modarai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Raimondo Ascione, University of Bristol, Bristol, United Kingdom

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