Major cardiovascular events after bone marrow mononuclear cell transplantation following acute myocardial infarction: an updated post-BAMI meta-analysis of randomized controlled trials

Abstract

Background The effect of bone marrow-derived mononuclear cells (BM-MNCs) after acute myocardial infarction (AMI) on myocardial function indices such as left ventricular ejection fraction has been widely studied. However, the effect of this intervention on major adverse cardiovascular events (MACE) was not the principal purpose of most investigations and its role is unclear. The aim of this study was to investigate the possible long-term clinical efficacy of BM-MNCs on MACE after AMI. Methods A comprehensive search was conducted through electronic databases for potentially eligible randomized trials investigating the impact of BM-MNC therapy following acute MI on clinical outcomes. Risk of bias of the eligible studies was assessed using the Cochrane Collaboration’s tool. The effect of treatment was displayed by risk ratio (RR) and its 95% confidence interval (CI) using random-effects model. Results Initial database searching found 1540 records and 23 clinical trials with a total of 2286 participants eligible for meta-analysis. Injection of BM-MNCs was associated with lower risk of composite end points of hospitalization for congestive heart failure (CHF), re-infarction, and cardiac-related mortality (91/1191 vs. 111/812, RR = 0.643, 95% CI = 0.489 to 0.845, p = 0.002). This effect was derived from both reduction of CHF (47/1220 vs. 62/841, RR = 0.568, 95% CI = 0.382 to 0.844, p = 0.005) and re-infarction rate (23/1159 vs. 30/775, RR = 0.583, 95% CI = 0.343 to 0.991, p = 0.046), but not cardiac-related mortality (28/1290 vs. 31/871, RR = 0.722, 95% CI = 0.436 to 1.197, p = 0.207). Conclusion This is the first meta-analysis focused on the cardiovascular outcomes of stem cell therapy after AMI and it revealed that transplantation of BM-MNCs may reduce composite endpoint of hospitalization for CHF, re-infarction, and cardiac related mortality driven mainly by reducing reinfarction and hospitalization for heart failure rates but not cardiovascular mortality.

Effect of once versus twice intracoronary injection of allogeneic-derived mesenchymal stromal cells after acute myocardial infarction: BOOSTER-TAHA7 randomized clinical trial

“…A Cochrane meta-analysis showed that treating AMI patients with a reduced LVEF with BM-MNCs effectively increases LVEF, yielding survival and functional benefits in patients below 55 with an EF below 37% [ 33 ]. On the other hand, two more recent meta-analyses found that while post-AMI therapy with BM-MNCs can decrease hospitalization for CHF and re-infarction, their effect on all-cause mortality and stroke rate is questionable [ 29 , 30 ]. Another cell type is MSCs, which were about twice as effective as BM-MNCs in the TAC-HFT trial [ 20 ].…”

Human Stem Cells for Cardiac Disease Modeling and Preclinical and Clinical Applications—Are We on the Road to Success?

“…More details about HSCs and MSCs are addressed later in this review. Their abundance and accessibility allow autologous implantation without previous expansion, which prevents stem cell differentiation and immune rejection and promotes cellular migration to the affected tissues [ 20 ]. A recent meta-analysis showed improved myocardial performance after BMMNCs transplantation and reduced rehospitalization and reinfarction rates, although no effect on reduction of cardiovascular-related death was observed [ 21 ].…”

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

“…However, the BAMI researchers observed the clinical benefit of reduced heart failure associated hospitalization in patients receiving BMNC therapy (45). In a recent meta-analysis study, Attar et al further confirmed that BMNC therapy improved clinical outcomes in terms of reinfarction and hospitalization for heart failure (46). Thus, it is crucial to identify a better cell type, optimal dose, and route of transplantation to strengthen the therapeutic effect and achieve a statistical significance in the post-BAMI era (10).…”