Bone marrow cells as therapy for ischaemic cardiomyopathy

Two trials in the Journal of the American Medical Association (JAMA) address the impact of bone marrow-derived cell therapy on safety and surrogate endpoints in patients with ventricular dysfunction due to ischaemic heart disease.

In the Timing in Myocardial Infarction Evaluation (TIME) trial, autologous bone marrow mononuclear (BMC) cells were given as an intracoronary infusion at day 3 or day 7 post catheterisation for ST-elevation myocardial infarction. All patients had a left ventricular ejection fraction of <46%, and the primary end points were change in global left ventricular ejection fraction, and regional wall motion in infarct and border zones at 6 months as measured by cardiac MRI. At 6 months, there was no significant increase in left ventricular ejection fraction for the BMC group compared to the placebo group, nor were any significant regional wall differences noted in infarct or border zones. The timing of treatment also had no effect on global or regional ventricular recovery.

In the POSEIDON study, mesenchymal stem cells (MSCs) were delivered myocardially to patients with established ischaemic cardiomyopathy; the goal of the trial was to compare the safety and efficacy of donor (allogeneic) MSCs compared to self-derived (autologous) MSCs. Both allogeneic and autologous MSCs decreased infarct size, but neither increased ejection fraction overall. Only allogeneic MSCs reduced left ventricular end-diastolic volumes, while autologous MSCs were associated with an improved 6-minute walk test and Minnesota Questionnaire score. Both allogeneic and autologous cells were associated with low rates of treatment-emergent adverse effects.

Conclusions:

In these two trials examining the use of bone-marrow derived cells in patients suffering from ischaemic heart disease, the use of bone marrow derived mononuclear cells did not improve ventricular function after acute infarction, while mesenchymal stem cells led to some improvement in functional capacity and ventricular remodelling in established ischaemic cardiomyopathy.

• Marban E, Malliaras K et al. Mixed Results for Bone Marrow-Derived Cell Therapy for Ischemic Heart Disease. JAMA 2012;308:2405-2406.

• Traverse JH, Henry TD, Pepine CJ et al. Effect of the Use and Timing of Bone MarrowMononuclear Cell Delivery on Left VentricularFunction After Acute Myocardial Infarction. The TIME Randomized Trial. JAMA 2012;308:2380-2389.

• Hare JM, Fishman JE, Gerstenblith G et al. Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy. The POSEIDON Randomized Trial. JAMA 2012;308:2369-2379

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