HYUNSOO KIM, Su Hyun Kim et al.
[Postmarketing Study] Safety and Effects on Left Ventricular Function of Coronary Artery Injection of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Anterior Wall Acute Myocardial Infarction
Research Summary
Of 26 patients who underwent stent placement for anterior wall acute myocardial infarction, 14 received mesenchymal stem cells cultured from their own bone marrow and injected into their coronary arteries one month later. Four months later, the left ventricular ejection fraction—a measure of the heart’s pumping function—increased by 8.8 percentage points in the treatment group and 4.8 percentage points in the control group, with no serious complications. However, heart size remained unchanged, and since these are interim results based on 26 patients, it is too early to generalize the findings. |
Study Results
Patients who underwent stent placement for anterior wall acute myocardial infarction received an injection of autologous bone marrow-derived mesenchymal stem cells into their coronary arteries approximately one month later. The primary endpoint was the change in left ventricular ejection fraction (LVEF; the percentage of blood ejected by the heart with each contraction) at the 4-month mark.
As assessed by SPECT, ejection fraction at the 4-month mark increased by 8.8 percentage points (±2.9) in the treatment group and by 4.8 percentage points (±1.9) in the control group (P = 0.031). Echocardiography also showed an increase of 9.0 percentage points in the treatment group and 5.3 percentage points in the control group at 4 months (P = 0.023), and 9.9 percentage points in the treatment group and 6.5 percentage points in the control group at 12 months (P = 0.048). However, there was no difference between the two groups in left ventricular volume, a measure of heart size.
Bone marrow aspiration and cell infusion were completed without complications; there were no cases of inflammation or bleeding at the aspiration site, nor were there any procedure-related arrhythmias, thrombi, or vascular dissections. During the 4- and 12-month follow-up periods, neither group experienced death, reinfarction, rehospitalization for heart failure, reintervention, stent thrombosis, or cerebral infarction. A small number of patients in both groups showed ventricular premature beats and atrial fibrillation on electrocardiograms, but there was no difference between the two groups.
Figure. Changes in left ventricular ejection fraction in the treatment and control groups (baseline → 4 months).
Study Design
This was a randomized, open-label clinical trial conducted at a single hospital in Korea from January 2012 to May 2015. The study included patients who had undergone stent implantation for acute anterior wall inferior left anterior descending (LAD) myocardial infarction and had a left ventricular ejection fraction (LVEF) of 40% or less. Of the 30 patients who provided informed consent, 4 were excluded because they did not undergo SPECT; the remaining 26 were assigned to the treatment group (14 patients) and the control group (12 patients) and were all included in the analysis. The control group received only standard medical therapy and did not undergo bone marrow aspiration or placebo procedures.
The primary endpoint was the change in left ventricular ejection fraction measured by SPECT at 4 months; secondary endpoints included left ventricular volume and major cardiac events. SPECT scans were performed 3–5 days and 4 months after the procedure, while echocardiograms were performed at 4 and 12 months.
Cells Used and Administration Method
On average, 3.0 days after admission, 20–25 mL of bone marrow was collected from the posterior iliac crest under local anesthesia and cultured into autologous bone marrow-derived mesenchymal stem cells at Pamisell’s GMP facility; The time from collection to administration averaged 25.0 days (±2.4). The release criteria were at least 95% positive for CD105, CD73, and CD90, and no more than 2% positive for CD45, CD34, and CD14.
The average dose per patient was 7.2 × 10⁷ cells. On average, 30 days after stent placement, a balloon catheter was inserted into the left anterior descending artery, and the balloon was inflated at low pressure from inside the stent to occlude blood flow for 2–3 minutes while the cells were infused. This procedure was repeated three times, with blood flow restored for 3 minutes between each repetition.
Discussion
This study demonstrates that the intra-coronary administration of mesenchymal stem cells approximately one month after an anterior wall acute myocardial infarction was feasible without major complications and improved left ventricular ejection fraction at the 4-month mark. The difference of approximately 4.0 percentage points between the two groups is similar to the 4.3% observed in a previous study using the same cells.
The researchers stated that the increase in ejection fraction was due to improved wall motion at the edge of the infarct, and that the lack of reduction in left ventricular volume was a result of the inability to fully restore cardiac structure.
There are also clear limitations. The researchers noted that the sample size was small, the data were collected at an early stage—midway through a 2-year follow-up study—and the methods for measuring left ventricular function were limited. It is also important to note that the study used an open-label design without a placebo control group, and all 26 participants were male. This study was conducted without external funding.
