Effect of once versus 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 exert a paracrine effect, which might be augmented if repeated doses are administered. This study aimed to compare the effects of single versus 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 10 days later. The primary endpoint was the 6-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 10 days later augmenting this effect. Trial registration: Trial registration: Iranian Registry of Clinical Trials, IRCT20201116049408N1. Retrospectively Registered 20 Nov. 2020, https://en.irct.ir/trial/52357