Effect of Once vs. Twice Intracoronary Injection of Allogeneic-Derived Mesenchymal Stromal Cells after Acute Myocardial Infarction: BOOSTER-TAHA7 Randomized Clinical Trial

Abstract

Background: Mesenchymal stromal cell (MSC) transplantation can improve the left ventricular ejection fraction (LVEF) after an acute myocardial infarction (AMI). Transplanted MSCs apparently exert a paracrine effect, which might be augmented if repeated doses are administered. This study aimed to compare the effects of single vs.double transplantation of Wharton’s jelly MSCs (WJ-MSCs) on LVEF post-AMI. Methods: We conducted a single-blind, randomized, multicenter trial. After 3-7 days of an AMI treated successfully by primary PCI, 70 patients younger than 65 with LVEF <40% on baseline echocardiography were randomized to receive conventional care, a single intracoronary infusion of WJ-MSCs, or a repeated infusion ten days later. The primary endpoint was the six-month LVEF improvement as per cardiac magnetic resonance (CMR) imaging. Results: The mean baseline EF measured by CMR was similar (~40%) in all three groups. By the end of the trial, while all patients experienced a rise in EF, the most significant change was seen in the repeated intervention group. Compared to the control group (n=25), single MSC transplantation (n=20) improved the EF by 4.54 ± 2%, and repeated intervention (n=20) did so by 7.45 ± 2% when measured by CMR imaging (P<0.001); when evaluated by echocardiography, these values were 6.71 ± 2.4 and 10.71 ± 2.5%, respectively (P<0.001). Conclusions: Intracoronary transplantation of WJ-MSCs 3-7 days after AMI in selected patients significantly improves LVEF, with the infusion of a booster dose ten days later augmenting this effect. Trial registration: Trial registration: Iranian Registry of Clinical Trials, IRCT20201116049408N1. Registered 20 Nov. 2020 - Retrospectively registered, https://en.irct.ir/trial/52357