Article

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) After Acute Myocardial Infarction

Department of Medicine, Cardiovascular Division and the Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 12/2009; 54(24):2277-86. DOI: 10.1016/j.jacc.2009.06.055
Source: PubMed

ABSTRACT

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).

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Available from: Gary Schaer, Apr 01, 2014
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    • "Originally, the therapeutic potential of these cells was thought to arise through their putative capacity to transdifferentiate, thereby directly contributing to vasculogenesis and tissue regeneration (Quevedo et al., 2009). This attractive hypothesis led to the prompt, perhaps immature transition of the results obtained in animal models to the clinics, with the ambitious goal to regenerate ischemic tissues (Hare et al., 2009; Tateishi- Yuyama et al., 2002). However, MSC plasticity has been later harshly questioned (Noiseux et al., 2006), and the therapeutic potential of these cells is currently considered to derive from the secretion of a variety of growth factors and cytokines exerting a paracrine, protective effect on ischemic cells (Gnecchi et al., 2012). "
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    • "This impaired electrical coupling results in abnormally slow conduction velocities thereby promoting impulse reentry leading to an increased risk for arrhythmic events [11]. From a therapeutic standpoint, bone marrow-derived MSCs are advantageous due to their ability to home in on sites of injury and their lack of cell surface markers used by immune system to recognize foreign antigens [12]. As such, these MSCs can be obtained from unrelated donors and used as an ''off-the-shelf'' form of cardiac stem cell therapy. "
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    • "Eventually clinical trials ensued. The first of these was a randomized, double blinded, placebo controlled phase 1 dose escalation study using intravenous allogeneic BM-MSC infusions after MI (Hare et al. 2009). Here, MSC treatment appeared safe after twelve months of follow up. "
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