Our aim was to investigate the safety and efficacy of intravenous allogeneic human
mesenchymal stem cells (hMSCs) in patients with myocardial infarction (MI).
Bone marrow-derived hMSCs may ameliorate consequences of MI, and have the advantages
of preparation ease, allogeneic use due to immunoprivilege, capacity to home to injured
tissue, and extensive pre-clinical support.
We performed a double-blind, placebo-controlled, dose-ranging (0.5, 1.6, and 5 million
cells/kg) safety trial of intravenous allogeneic hMSCs (Prochymal, Osiris Therapeutics,
Inc., Baltimore, Maryland) in reperfused MI patients (n=53). The primary end point
was incidence of treatment-emergent adverse events within 6 months. Ejection fraction
and left ventricular volumes determined by echocardiography and magnetic resonance
imaging were exploratory efficacy end points.
Adverse event rates were similar between the hMSC-treated (5.3 per patient) and placebo-treated
(7.0 per patient) groups, and renal, hepatic, and hematologic laboratory indexes were
not different. Ambulatory electrocardiogram monitoring demonstrated reduced ventricular
tachycardia episodes (p=0.025), and pulmonary function testing demonstrated improved
forced expiratory volume in 1 s (p=0.003) in the hMSC-treated patients. Global symptom
score in all patients (p=0.027) and ejection fraction in the important subset of anterior
MI patients were both significantly better in hMSCs versus placebo subjects. In the
cardiac magnetic resonance imaging substudy, hMSC treatment, but not placebo, increased
left ventricular ejection fraction and led to reverse remodeling.
Intravenous allogeneic hMSCs are safe in patients after acute MI. This trial provides
pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived
stem cell in post-infarction patients. (Safety Study of Adult Mesenchymal Stem Cells
[MSC] to Treat Acute Myocardial Infarction; NCT00114452).