Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial

Abstract

Background & objectives:Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy.Methods:In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI).Results:On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 × 108(n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study.Interpretation & conclusions:Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

National multicentric M13 Stem Cell Trial reports negative outcome - Need to look at VSELs as an alternative to bone marrow MNCs for cardiac regeneration

“…I read with great interest the article by Nair et al 1 on a multicentric autologous stem cell trial for patients with acute myocardial infarction (AMI). This was undertaken on the basis of promising results in a pilot ABCD (Autologous Bone marrow Cells in Dilated cardiomyopathy) study reported from All India Institute of Medical Sciences (AIIMS), New Delhi2.…”

“…As mentioned in the introduction of the article1, the transplanted mononuclear cells may exert a paracrine effect, engraft and integrate with host myocardium to bring about regeneration, may help remodel extracellular matrix or improve neo-vascularization or recruit endogenous stem cells. There is some clarity on this now since 2007 when the present clinical trial was initiated by Nair et al 1.…”

“…There is some clarity on this now since 2007 when the present clinical trial was initiated by Nair et al 1. Firstly, we need to accept the fact that bone marrow transplantation (BMT) has been successful over decades to cure haematological disorders and is a standard method of care because BM mononuclear cells harbour a sub-population of haematopoietic stem cells (HSCs) which are already committed to haematological fate and thus can regenerate and cure blood disorders7.…”

“…It is not clear as to why Nair et al 1 did not use VSELs rather than bone marrow MNCs. Miyanishi et al 31 were unable to detect VSELs by flow cytometry despite using published protocols and the same equipment.…”

“…It will be ideal for Nair et al 1 to modify their isolation protocols to include VSELs (for regeneration) and MSCs (as a source of growth factors and cytokines) in their trials in future rather than transplanting MNCs in more number of patients. HSCs do not trans-differentiate and regenerate the cardiac tissue.…”