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Meta-Analysis
. 2012 Jul 31;126(5):551-68.
doi: 10.1161/CIRCULATIONAHA.111.086074. Epub 2012 Jun 22.

Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis

Vinodh Jeevanantham  1 , Matthew Butler, Andre Saad, Ahmed Abdel-Latif, Ewa K Zuba-Surma, Buddhadeb Dawn
Affiliations
Meta-Analysis

Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis

Vinodh Jeevanantham et al. Circulation. .

Abstract

Background: Despite rapid clinical translation and widespread enthusiasm, the therapeutic benefits of adult bone marrow cell (BMC) transplantation in patients with ischemic heart disease continue to remain controversial. A synthesis of the available data is critical to appreciate and underscore the true impact of this promising approach.

Methods and results: A total of 50 studies (enrolling 2625 patients) identified by database searches through January 2012 were included. Weighted mean differences for changes in left ventricular (LV) ejection fraction, infarct size, LV end-systolic volume, and LV end-diastolic volume were estimated with random-effects meta-analysis. Compared with control subjects, BMC-treated patients exhibited greater LV ejection fraction (3.96%; 95% confidence interval, 2.90-5.02; P<0.00001) and smaller infarct size (-4.03%, 95% confidence interval, -5.47 to -2.59; P<0.00001), LV end-systolic volume (-8.91 mL; 95% confidence interval, -11.57 to -6.25; P<0.00001), and LV end-diastolic volume (-5.23 mL; 95% confidence interval, -7.60 to -2.86; P<0.0001). These benefits were noted regardless of the study design (randomized controlled study versus cohort study) and the type of ischemic heart disease (acute myocardial infarction versus chronic ischemic heart disease) and persisted during long-term follow-up. Importantly, all-cause mortality, cardiac mortality, and the incidence of recurrent myocardial infarction and stent thrombosis were significantly lower in BMC-treated patients compared with control subjects.

Conclusions: Transplantation of adult BMCs improves LV function, infarct size, and remodeling in patients with ischemic heart disease compared with standard therapy, and these benefits persist during long-term follow-up. BMC transplantation also reduces the incidence of death, recurrent myocardial infarction, and stent thrombosis in patients with ischemic heart disease.

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Figures

Figure 1
Figure 1
Flow diagram of eligible studies of bone marrow–derived cell (BMC) transplantation in patients with acute myocardial infarction and chronic ischemic heart disease. GCSF indicates granulocyte colony-stimulating factor; and RCT, randomized controlled trial. IV, inverse variance.
Figure 2
Figure 2
Forest plot of unadjusted difference in mean (with 95% confidence intervals [CIs]) change in left ventricular ejection fraction (LVEF) in patients treated with bone marrow-derived cells (BMCs) compared with controls. The figure shows the summary of randomized controlled trials (RCTs) and cohort studies. Transplantation of BMCs resulted in a 3.96% (CI: 2.90, 5.02; P<0.00001) increase in mean LVEF. The overall effect was statistically significant in favor of BMC transplantation. WMD indicates weighted mean difference. IV, inverse variance.
Figure 3
Figure 3
Forest plot of unadjusted difference in mean (with 95% confidence intervals [CIs]) change in infarct scar size in patients treated with bone marrow-derived cells (BMCs) compared with controls. The figure shows the summary of randomized controlled trials (RCTs) and cohort studies. Transplantation of BMCs resulted in a 4.03% (CI: –5.47, –2.59; P<0.00001) decrease in mean infarct scar size. The overall effect was statistically significant in favor of BMC transplantation. WMD indicates weighted mean difference. IV, inverse variance.
Figure 4
Figure 4
Forest plot of unadjusted difference in mean (with 95% confidence intervals [CIs]) change in left ventricular end-systolic volume (LVESV) in patients treated with bone marrow-derived cells (BMCs) compared with controls. The figure shows the summary of randomized controlled trials (RCTs) and cohort studies. Transplantation of BMCs resulted in a 8.91 ml (CI: – 11.57, –6.25; P<0.00001) decrease in LVESV. The overall effect was statistically significant in favor of BMC transplantation. WMD indicates weighted mean difference. IV, inverse variance.
Figure 5
Figure 5
Forest plot of unadjusted difference in mean (with 95% confidence intervals [CIs]) change in left ventricular end-diastolic volume (LVEDV) in patients treated with bone marrow-derived cells (BMCs) compared with controls. The figure shows the summary of randomized controlled trials (RCTs) and cohort studies. BMC transplantation resulted in a 5.23 ml (CI: – 7.60, –2.86; P<0.001) decrease in mean LVEDV. The overall effect was statistically significant in favor of BMC transplantation. WMD indicates weighted mean difference. IV, inverse variance.
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