Efficacy of Mesenchymal Stem Cell Transplantation on Major Cardiovascular Events and Paraclinical Parameters in Ischemic and Non-Ischemic Heart Failure Patients and the Factors Influencing these Effects: A Meta‑Analysis of Randomized Controlled Trials

Abstract

Background Trials investigating the effect of mesenchymal stem cells (MSCs) on heart failure (HF) have been controversial. This study was conducted to investigate whether the transplantation of MSCs after HF could help improve clinical outcomes and myocardial performance indices. Methods Using a systematic approach, electronic databases were searched for randomized controlled trials (RCTs), which evaluated the transplantation of MSCs after HF. The outcomes of interest included clinical outcomes and myocardial function indices. We also assessed the role of age, cause of heart failure, cell origin, cell number, type of donor (autologous/allogeneic), and route of cell delivery on these outcomes. Using the random-effects method, a relative risk (RR) or mean difference (MD) and their corresponding 95% confidence intervals (CI) were pooled. Results Seventeen RCTs including 1684 patients (927 and 757 patients in the intervention and control arms, respectively) were enrolled. The RR (95% CI) of mortality was 0.78 (0.62; 0.99, p = 0.04) in the MSC group compared to the controls. HF rehospitalization decreased in MSC group (RR = 0.85 (0.71 to 1.01), p = 0.06), but this was only significant in those who received autologous MSCs (RR = 0.67 (0.49; 0.90), p = 0.008). LVEF was significantly increased among those who received MSC (MD = 3.38 (1.89; 4.87), p < 0.001). LVESV (MD= -9.14 (-13.25; -5.03), p < 0.001), LVEDV (MD= -8.34 (-13.41; -3.27), p < 0.001), and scar size (standardized MD= -0.32 (-0.60; -0.05), p = 0.02) were significantly decreased. NYHA class (MD= -0.19 (-0.34; -0.06), p = 0.006), BNP level (standardized MD= -0.28 (-0.50; -0.06), p = 0.01), and MLHFQ (MD= -11.55 (-16.77; -6.33), p = 0.005) significantly decreased and 6-minute walk test significantly improved (MD = 36.86 (11.22; 62.50), p = 0.001) in the MSC group. Trials were not affected by the participants’ etiology of heart failure, while trials with the autologous source of cells, MSC doses lower than 100 million cells, and intracoronary injection performed significantly better in some of the outcomes. Conclusion Transplantation of MSCs for ischemic or dilated heart failure patients may reduce all-cause mortality and improve clinical condition. Moreover, this treatment would improve left ventricular function indices and reduce scar size.