Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion

• DOI: 10.3389/fcvm.2023.1186574
• Publication Date: 2023-06-05T05:23:35Z
• Authors: Luís Raposo; Rui J. Cerqueira; Sara Leite; Liliana Moreira-C...; Tiago L. Laundos; Joana O. Miranda; Pedro Mendes-Ferr...; João Almeida Coelho; Rita N. Gomes; Perpétua Pinto-do-Ó; Diana S. Nascimento; André P. Lourenço; Nuno Cardim; Adelino Leite-Mor...
• Keywords: Preload; Contractility

Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers recovery a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery xenogeneic hUCM-MSC as reperfusion-adjuvant therapy translational model AMI swine.In placebo-controlled trial, pot-belied pigs were randomly assigned to sham-control group (vehicle-injection; n = 8), + vehicle (n 12) or IC-injection 11) 5 × 105 hUCM-MSC/Kg, within 30 min reperfusion. was created percutaneously by balloon occlusion mid-LAD. Left-ventricular function blindly evaluated at 8-weeks invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship skinned cardiomyocytes gene expression RNA-sequencing.As compared vehicle, enhanced systolic shown higher ejection fraction (65 ± 6% vs. 43 4%; p 0.0048), cardiac index (4.1 0.4 3.1 0.2 L/min/m2; 0.0378), preload recruitable stroke work (75 13 36 4 mmHg; 0.0256) end-systolic elastance (2.8 0.7 2.1 mmHg*m2/ml; 0.0663). Infarct size non-significantly lower cell-treated animals (13.7 2.2% 15.9 2.7%; Δ -2.2%; 0.23), interstitial fibrosis cardiomyocyte hypertrophy remote myocardium. Sarcomere active tension improved, genes related extracellular matrix remodelling (including MMP9, TIMP1 PAI1), collagen fibril organization glycosaminoglycan biosynthesis downregulated treated with hUCM-MSC.Intracoronary transfer shortly after reperfusion improved left-ventricular function, which could not be explained observed extent infarct reduction alone. Combined contributions favourable modification fibrosis, contractility myocardium may provide mechanistic insight for biological effect.