Percutaneous Adventitial Delivery of Allogeneic Bone Marrow Derived Stem Cells Via Infarct Related Artery Improves Long-term Ventricular Function in Acute Myocardial Infarction
Satish Medicetty1, Dominikt Wiktor2, Nicholas Lehman1, Amy Raber1, Zoran B. Popović2, Robert Deans1, Anthony E. Ting1, Marc S. Penn2
1 Regenerative Medicine Department, Athersys, Inc., Cleveland, OH
2 Skirball Laboratory for Cardiovascular Cellular Therapeutics, Departments of Stem Cell Biology and Regenerative Medicine and Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
Background: Acute myocardial infarction (AMI) results in ischemic damage and death of cardiomyocytes and loss of vasculature. Stem cell therapy has emerged as a potentially promising strategy for maximizing cardiac function following ischemic injury. Issues of cell source, delivery and quantification of response have challenged development of clinically viable strategies. In this study we investigate the effects of a well defined bone marrow derived allogeneic cell product delivered by catheter directly to the myocardium via the infarct related vessel on global and regional measures of left ventricular (LV) function in a porcine model of anterior wall myocardial infarction.
Methods and Results: Multipotent adult progenitor cells (MAPCs) were derived and expanded from the bone marrow of a donor Yorkshire pig. Anterior wall myocardial infarction (AMI) was induced by 90 minutes of mid LAD occlusion using a balloon catheter. Two days after AMI was induced, either vehicle (Plasma Lyte-A, n=7), low dose (20 million, n=6) or high dose (200 million, n=6) MAPCs were delivered directly to the myocardium via the infarct related vessel using a transarterial microsyringe catheter-based delivery system. Echocardiography was used to measure LV function as a function of time after AMI. Animals that received low dose cell treatment showed significant improvement in regional and global LV function and remodeling compared to the high dose or control animals.
Conclusion: Direct myocardial delivery of allogeneic MAPCs two days following AMI through the vessel wall of the infarct related vessel is safe and results in delivery of cells throughout the infarct zone and improved cardiac function despite lack of long-term cell survival. These data further support the hypothesis of cell based myocardial tissue repair by a paracrine mechanism and suggest a clinically translatable strategy for delivering cells at any time after AMI to modulate cardiac remodeling and function.
Cell Transplantation 2011 Oct 14 [Epub ahead of print]. ©2010 SIR. Published by Elsevier Inc.
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