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(Circulation. 2009;120:S238-S246.)
© 2009 American Heart Association, Inc.

Cell Transplantation and Tissue Regeneration

Stem Cells for Myocardial Repair With Use of a Transarterial Catheter

Xiaohong Wang, MD, PhD; Mohammad Nurulqadr Jameel, MD; Qinglu Li, BS; Abdul Mansoor, MD, PhD; Xiong Qiang, MS; Cory Swingen, PhD; Carmelo Panetta, MD; Jianyi Zhang, MD, PhD

From the Department of Medicine, University of Minnesota Medical School, Minneapolis, Minn.

Correspondence to Jianyi Zhang, MD, PhD, University of Minnesota Health Science Center, Mayo Mail Code 508, 420 Delaware St SE, Minneapolis, MN 55455. E-mail zhang047{at}umn.edu

Background— Using a swine model of postinfarction left ventricle (LV) remodeling, we investigated marrow-derived, multipotent progenitor cell (MPC) transplantation into hearts with acute myocardial infarction (AMI) via a novel transarterial catheter.

Methods and Results— The left anterior descending coronary artery was balloon-occluded after percutaneous transluminal angiography to generate AMI (60-minute no-flow ischemia). The transarterial catheter was then placed in the same coronary artery, and either 50x10⁶ MPCs (cell group, n=6) or saline (control, n=6) was injected into the border zone (BZ) myocardium. LV function was assessed by magnetic resonance imaging before AMI and at 1 and 4 weeks after AMI, whereas myocardial energy metabolism was assessed by ³¹P-magnetic resonance spectroscopy at week 4. One week after AMI, the ejection fraction was significantly reduced in both groups from a baseline of 50% to 31.3±3.9% (cell group) and 33.3±3.1% (control). However, at week 4, the cell group had a significant recovery in ejection fraction. The functional improvements were accompanied by a significant improvement in myocardial bioenergetics. Histologic data demonstrated a 0.55% cell engraftment rate 4 weeks after MPC transplantation. Only 2% of engrafted cells were costaining positive for cardiogenic markers. Vascular density in the BZ was increased in the cell group. Conditioned medium from cultured MPCs contained high levels of vascular endothelial growth factor, which was increased in response to hypoxia. MPCs cocultured with cardiomyocytes inhibited changes in cardiomyocyte mitochondrial membrane potential and cytochrome c release induced by tumor necrosis factor-.

Conclusions— Thus, a paracrine effect may contribute significantly to the observed therapeutic effects of MPC transplantation.

Key Words: stem cells • metabolism • myocardial infarct