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Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model

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Abstract

Heart failure with preserved ejection fraction (HFpEF) is a major public health concern. Its outcome is poor and, as of today, barely any treatments have been able to decrease its morbidity or mortality. Cardiosphere-derived cells (CDCs) are heart cell products with anti-fibrotic, anti-inflammatory and angiogenic properties. Here, we tested the efficacy of CDCs in improving left ventricular (LV) structure and function in pigs with HFpEF. Fourteen chronically instrumented pigs received continuous angiotensin II infusion for 5 weeks. LV function was investigated through hemodynamic measurements and echocardiography at baseline, after 3 weeks of angiotensin II infusion before three-vessel intra-coronary CDC (n = 6) or placebo (n = 8) administration and 2 weeks after treatment (i.e., at completion of the protocol). As expected, arterial pressure was significantly and similarly increased in both groups. This was accompanied by LV hypertrophy that was not affected by CDCs. LV systolic function remained similarly preserved during the whole protocol in both groups. In contrast, LV diastolic function was impaired (increases in Tau, LV end-diastolic pressure as well as E/A, E/E’septal and E/E’lateral ratios) but CDC treatment significantly improved all of these parameters. The beneficial effect of CDCs on LV diastolic function was not explained by reduced LV hypertrophy or increased arteriolar density; however, interstitial fibrosis was markedly reduced. Three-vessel intra-coronary administration of CDCs improves LV diastolic function and reduces LV fibrosis in this hypertensive model of HFpEF.

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Acknowledgements

The authors wish to thank Jackelyn VALLE for her technical help.

Funding

This study was supported by a grant from a “Subvention Transplantation et Thérapie Cellulaire 2018 FRM” [PME20180639527].

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Authors and Affiliations

  1. Inserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d’Alfort, Maisons-Alfort, France

    Romain Gallet, Jin-Bo Su, Daphné Corboz, Paul-Matthieu Chiaroni, Alain Bizé, Jianping Dai, Juliette Brehat, Lucien Sambin, Guillaume Thery, Aurélien de Pommereau, Pierre Denormandie, Emmanuel Teiger & Bijan Ghaleh

  2. Assistance Publique–Hôpitaux de Paris, Hôpital Henri Mondor, Service de Cardiologie, Créteil, France

    Romain Gallet, Paul-Matthieu Chiaroni & Emmanuel Teiger

  3. Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Eduardo Marbán

  4. PhyMedExp, Université de Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France

    Mathieu Panel & Alain Lacampagne

  5. Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, PSL Research University, Paris, France

    Pierre Boucher, Gaëtan Pallot & Stéphane Germain

  6. Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Département de biochimie-pharmacologie-biologie moléculaire-génétique médicale, Créteil, France

    Nadir Mouri

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  1. Romain Gallet
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Corresponding author

Correspondence to Bijan Ghaleh.

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Conflict of interest

EM holds founder’s equity in Capricor Therapeutics.

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Gallet, R., Su, JB., Corboz, D. et al. Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model. Basic Res Cardiol 118, 26 (2023). https://doi.org/10.1007/s00395-023-00995-2

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