Effect of Bone Marrow–Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction

Abstract

Rationale: Intracoronary delivery of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). Objective: To demonstrate long-term efficacy of BM-MNC treatment after AMI. Methods and Results: In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was −1.9±9.8% for control (mean±SD), −0.9±10.5% for the early treatment group, and −0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). Conclusions: Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00355186.

New Treatment Strategies for Alcohol-Induced Heart Damage

“…They showed non-homogeneous and diverse functional results [159,161]. A European BAMI multi-centric trial on the effect of intracoronary reinfusion of bone marrow-derived mononuclear cells is ongoing and may provide new data [162]. Mesenchymal stem cells (MSC), either autologous or allogeneic, have been established as one of the potential therapeutic agents in cardiac regeneration.…”

The modest outcome of clinical trials with bone marrow cells for myocardial repair: is the autologous source of cells the prime culprit?

“…The data thus generated was analysed to determine changes in different end-points including LVEF, LVEDV, LVESV, NT-proBNP values between the three treatment arms over time, i.e., between baseline, 4 months and 12 months using a multivariable linear regression model for repeated measures. Treatment arms were compared at baseline using the Kruksal Wallis test and the Fisher exact test for continuous and categorical data respectively (12). However, it is unclear which statistical tests were applied to analyse the data where combined events were calculated.…”

“…While discussing the study limitations, Sürder et al have rightly pointed out that the researchers in the field of stem cells are still uncertain about many of the fundamental issues ranging from the best cell type to the optimal time after MI for cell-based therapy despite more than decadelong efforts in the clinical settings (12). The autologous availability of the BM cells is considered as one of the major advantages associated with their use for cell-based therapy and hence, transplantation of autologous BM cells remains a communal feature of most clinical studies reported to date.…”

“…The patients were randomized to receive BM-MNCs at two stipulated time-points of 4-7 days and 3-4 weeks after MI whereas the control group received no cell therapy. The randomized study was designed as 1:1:1 for control and the two experimental groups and, was performed immediately after PCI in the culprit coronary artery to ascertain the optimal time of cell transplantation after MI and its impact on the outcome of the procedure (12). The same group of researchers have previously published 4-month followup data from the SWISS-AMI study which also showed little change in the LVEF in both early and late treatment…”

Consistently Inconsistent—Bone Marrow Mononuclear Stem Cell Therapy Following Acute Myocardial Infarction

“…Using autologous bone marrow mononuclear cells (BMCs) in patients with acute ST-segment myocardial infarction (STEMI), the trials were notable for their clear signal of safety, but discordant in their findings of benefit. Unfortunately, the 1-year results of the SWISS-AMI trial (4) reported in this issue of Circulation Research remind us again of the inability of BMC therapy in STEMI patients to demonstrate consistent benefit. Why are there such disparate results in trials using a similar cell product in a similar patient population?…”