Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights from Randomized Controlled Trials
Rationale: Notwithstanding the uncertainties regarding the outcomes of BMC therapy for heart repair, further insights are critically needed to improve this promising approach.
Objective: To delineate the true impact of BMC therapy for cardiac repair and gain insights for future trials through systematic review and meta-analysis of data from eligible randomized controlled trials (RCTs).
Methods and Results: Database searches through August 2014 identified forty-eight eligible RCTs (enrolling 2602 patients). Weighted mean differences for changes in left ventricular (LV) ejection fraction (EF), infarct size, LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were analyzed with random-effects meta-analysis. Compared with standard therapy, BMC transplantation improved LVEF (2.92%; 95% confidence interval [CI], 1.91 to 3.92; P<0.00001), reduced infarct size (-2.25%; 95% CI, -3.55 to -0.95; P=0.0007) and LVESV (-6.37 ml; 95% CI, -8.95 to -3.80; P<0.00001), and tended to reduce LVEDV (-2.26 ml; 95% CI, -4.59 to 0.07; P=0.06). Similar effects were noted when data were analyzed after excluding studies with discrepancies in outcomes reporting. The benefits also persisted when cardiac catheterization was performed in control patients as well. Although imaging modalities partly influenced the outcomes, LVEF improved in BMC-treated patients when assessed by MRI. Early (<48h) BMC injection after MI was more effective in reducing infarct size, while BMC injection between 3 and 10 days proved superior toward improving systolic function. A minimum of 50 million BMCs seemed to be necessary, with limited additional benefits seen with increasing cell numbers. BMC therapy was safe and improved clinical outcomes, including all-cause mortality, recurrent MI, ventricular arrhythmia, and cerebrovascular accident (CVA) during follow-up, albeit with differences between acute MI and chronic IHD subgroups.
Conclusions: Transplantation of adult BMCs improves LVEF, reduces infarct size and ameliorates remodeling in patients with IHD. These effects are upheld in analyses of studies employing MRI, and also after excluding studies with discrepant outcomes reporting. BMC transplantation may also reduce the incidence of death, recurrent MI, ventricular arrhythmia, and CVA during follow-up.
- acute myocardial infarction
- bone marrow mononuclear cells
- ischemic heart disease
- stem cell
- Received December 23, 2014.
- Revision received July 1, 2015.
- Accepted July 9, 2015.