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Intra-Coronary injection of human Umbilical Cord matrix derived Mesenchymal Stem Cells (hUCMSC) improves myocardial functional performance after acute myocardial infarction in a swine model of infarct-reperfusion
Session:
Posters 1 - Écran 08 - HTA / Fármacos /Ciência Básica
Speaker:
Luís Raposo
Congress:
CPC 2018
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.2 Basic Science - Cardiac Biology and Physiology
Session Type:
Posters
FP Number:
---
Authors:
Luís Raposo ; André Lourenço; Diana S. Nascimento; Rui Cerqueira; Tiago Laundos Santos; Sara Leite; Joana Miranda; Luisa Guardão; Helder Cruz; Pedro Cruz; Nuno Cardim; António Jacinto; Perpétua Pinto-do-Ó; Adelino Leite-Moreira
Abstract
<p><strong>Background</strong></p> <p>Stem cell-based therapies have been extensively investigated in the setting of acute myocardial infarction (MI) with the purpose of limiting scar formation and improving ejection fraction, both in animal models and in small human trials, with mixed results. Umbilical cord matrix-derived mesenchymal cells (hUCMSC) can be easily obtained at very high numbers, have both high functional potency and low immunogenicity and may be used as an allogeneic “off-the-shelf” product.</p> <p><strong>Aim</strong></p> <p>To access the effects of a single intracoronary injection (IC) of hUC-MSC on left ventricular performance and infarct size in a large animal preclinical model of reperfused MI.</p> <p><strong>Methods</strong></p> <p>In a sham and placebo controlled study, 31 male vietnamese pigs (37.6±9.3 Kg) were randomly assigned to a sham procedure (n=8), infarct with IC injection of vehicle (placebo; n=12) and infarct with IC administration of hUCMSC (n=11). Antero-apical MI was induced percutaneously by balloon occlusion of the mid-LAD during 120 minutes, after which reperfusion was allowed to occur. Within the next 30 min, infarcted animals blindly received an IC injection of placebo or hUCMSC (0.5x10<sup>6 </sup>cells/kg of body weight) trough a microcatheter. Survivors were treated with ramipril 2.5 mg and metoprolol 25 mg daily for the duration of the 8 week follow-up, after which final evaluation was performed, consisting of echocardiogram, invasive hemodynamic evaluation with a conductance catheter (n=19), at rest and with dobutamine challenge, and (collection) harvest of the heart (n=21) for histo-pathological and molecular biology studies.</p> <p><strong>Results</strong></p> <p>Only results of invasive hemodynamics and infarct area are reported here. In comparison to placebo, hUCMSC-treated animals had significantly higher (p<0.05) ejection fraction (65% vs. 43%), pre-load recruitable stroke work [PRSW] (75 vs. 36 mmHg), cardiac index (4.1 vs. 3.1 L/min*m<sup>2</sup>) and elastance [Ees<em><sub>i</sub></em>) (2.6 vs. 2.3 mmHg*m<sup>2</sup>/mL) at rest. With dobutamine challenge CI, PRSW and Ees<em><sub>i</sub></em> increased to a greater extent in the hUCMSC group. Infarct size (as % of LV area) was non-significantly lower in hUCMSC (13.2% vs. 15.9%; ?=1.7%); after excluding one animal from the active group which cell product had very low viability (77% vs. >89%), the difference in infarct size was 2.7% (ANOVA p=0.043 vs. placebo).</p> <p><strong>Conclusions</strong></p> <p>In this experience, IC administration of hUCMSC soon after reperfused MI, improved LV performance by interfering with both systolic and diastolic functional parameters. These effects appeared to be relatively independent from infarct size reduction.</p>
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