Comparative effectiveness of mesenchymal stem cell versus bone-marrow mononuclear cell transplantation in heart failure: a meta-analysis of randomized controlled trials

Abstract

Background: There is no clear evidence on the comparative effectiveness of bone-marrow mononuclear cell (BMMNC) vs. mesenchymal stromal cell (MSC) stem cell therapy in patients with chronic heart failure (HF).

Methods: Using a systematic approach, eligible randomized controlled trials (RCTs) of stem cell therapy (BMMNCs or MSCs) in patients with HF were retrieved to perform a meta-analysis on clinical outcomes (major adverse cardiovascular events (MACE), hospitalization for HF, and mortality) and echocardiographic indices (including left ventricular ejection fraction (LVEF)) were performed using the random-effects model. A risk ratio (RR) or mean difference (MD) with corresponding 95% confidence interval (CI) were pooled based on the type of the outcome and subgroup analysis was performed to evaluate the potential differences between the types of cells.

Results: The analysis included a total of 36 RCTs (1549 HF patients receiving stem cells and 1252 patients in the control group). Transplantation of both types of cells in patients with HF resulted in a significant improvement in LVEF (BMMNCs: MD (95% CI) = 3.05 (1.11; 4.99) and MSCs: MD (95% CI) = 2.82 (1.19; 4.45), between-subgroup p = 0.86). Stem cell therapy did not lead to a significant change in the risk of MACE (MD (95% CI) = 0.83 (0.67; 1.06), BMMNCs: RR (95% CI) = 0.59 (0.31; 1.13) and MSCs: RR (95% CI) = 0.91 (0.70; 1.19), between-subgroup p = 0.12). There was a marginally decreased risk of all-cause death (MD (95% CI) = 0.82 (0.68; 0.99)) and rehospitalization (MD (95% CI) = 0.77 (0.61; 0.98)) with no difference among the cell types (p > 0.05).

Conclusion: Both types of stem cells are effective in improving LVEF in patients with heart failure without any noticeable difference between the cells. Transplantation of the stem cells could not decrease the risk of major adverse cardiovascular events compared with controls. Future trials should primarily focus on the impact of stem cell transplantation on clinical outcomes of HF patients to verify or refute the findings of this study.

Keywords: Bone-marrow mononuclear cells; Chronic heart failure; Mesenchymal stem cells; Stem cell therapy.

Fig. 1

PRISMA flowchart demonstrating the search and screening process

Fig. 2

Risk of bias assessment

Fig. 3

Forest plot demonstrating the comparison of stem cell transplantation compared with placebo stratified by the type of cell A: MACE, B: all-cause mortality, and C: rehospitalization for heart failure (MACE: major adverse cardiovascular events, RR: risk ratio, CI: confidence interval, BMMNC: bone-marrow mononuclear cell, MSC: mesenchymal stem cell)

Fig. 4

Forest plot demonstrating the comparison of stem cell transplantation compared with placebo stratified by the type of cell A: LVEF, B: LVEDV, and C: LVESV (LVEF: left ventricular ejection fraction, LVEDV: left ventricular end-diastolic volume, LVESV: left ventricular end-systolic volume, MD: mean difference, CI: confidence interval, BMMNC: bone-marrow mononuclear cell, MSC: mesenchymal stem cell)

Fig. 5

Forest plot demonstrating the comparison of stem cell transplantation compared with placebo stratified by the type of cell A: 6MWT and B: BNP (6MWT: 6-min walk test, BNP: B-type natriuretic peptide, SMD: standardized mean difference, MD: mean difference, CI: confidence interval, BMMNC: bone-marrow mononuclear cell, MSC: mesenchymal stem cell)