Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: Systematic Review and Meta-analysis

Hyunsuk Jeong, Hyeon Woo Yim, Hun-Jun Park, Youngseung Cho, Hanter Hong, Na Jin Kim, Il-Hoan Oh, Hyunsuk Jeong, Hyeon Woo Yim, Hun-Jun Park, Youngseung Cho, Hanter Hong, Na Jin Kim, Il-Hoan Oh

Abstract

Background and objectives: Mesenchymal stem cells (MSC) have emerged as breakthrough treatments for myocardial infarction. However, the efficacy of MSC remains unclear. The aim of the study was to evaluate treatment effect of MSC in terms of mechanical, regenerative, and clinical outcomes for patients with myocardial infarction (MI) using meta-analysis.

Methods: A systematic search and critical review of MEDLINE, EMBASE, and Cochrane database literature published from inception through December 2017 was performed. The inclusion criteria were randomized controlled trials, studies on patients with myocardial infarction, and studies compared with placebo as a control group.

Results: A total of 950 patients from 14 randomized placebo controlled trials were included in the final meta-analysis. MSC treatment showed benefits for mechanical, regenerative, and clinical outcomes. In terms of mechanical outcomes, the LVEF of the MSC treatment group increased by 3.84% (95% CI: 2.32~5.35, I²=43) and the effect was maintained for up to 24 months. Regenerative outcomes were measured by scar mass and WMSI. Scar mass was reduced by -1.13 (95% CI: -1.80 to -0.46, I²=71) and WMSI was reduced by -0.05 (95% CI: -0.07 to -0.03, I²=45) at 6 months after MSC treatment. Mortality rate and incidence of re-hospitalization for HF in MSC group patients trended toward reduced incidence compared to the control group, although this was not statistically significant because of the low event rate.

Conclusions: The findings of this meta-analysis indicate that MSCs can be beneficial in improving heart function in the treatment of MI. However, the efficacy of MSCs must be further explored through large randomized controlled trials based on rigorous research design.

Keywords: Mesenchymal stem cell; Meta-analysis; Myocardial infarction; Systematic review.

Conflict of interest statement

Potential conflict of interest

The authors have no conflicting financial interest.

Figures

Fig. 1
Fig. 1
Flow diagram of study classification in this review.
Fig. 2
Fig. 2
MSC effect on mechanical outcomes. (A) LVEF (left ventricular ejection fraction); (B) LVESV (left ventricular end-systolic volume); (C) LVEDV (left ventricular end-diastolic volume); (D) WMSI (wall motion score index).
Fig. 2
Fig. 2
MSC effect on mechanical outcomes. (A) LVEF (left ventricular ejection fraction); (B) LVESV (left ventricular end-systolic volume); (C) LVEDV (left ventricular end-diastolic volume); (D) WMSI (wall motion score index).
Fig. 3
Fig. 3
MSC effect on regenerative and clinical outcomes. (A) Scar mass; (B) 6MWD (6-minute walking distance); (C) all-cause mortality; (D) re-hospitalization for heart failure (HF).
Fig. 4
Fig. 4
Mean changes of cardiac function with MSC compared to control at baseline and at 3, 6, 12, and 24-month follow-up. *Numbers in the table indicate the numbers of trials including analysis at each follow-up point. LVEF: left ventricle ejection fraction; LVEDV: left ventricle end-diastolic volume; LVESV: left ventricle end-systolic volume. Error bars indicated 95% Confidence Interval.

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