Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties.
Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n=7] had significantly higher LVEF than controls [n=8] (49+/-2% vs. 44+/-3%, P=0.015) and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P<or=0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium.


CONCLUSIONS
IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.
Price
Matthew J
MJ
Division of Cardiology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA.
Chou
Chung-Chuan
CC
Frantzen
Malka
M
Miyamoto
Takashi
T
Kar
Saibal
S
Lee
Steve
S
Shah
Prediman K
PK
Martin
Bradley J
BJ
Lill
Michael
M
Forrester
James S
JS
Chen
Peng-Sheng
PS
Makkar
Raj R
RR
D000818:Animals; D018929:Cell Culture Techniques; D017023:Coronary Angiography; D004195:Disease Models, Animal; D004452:Echocardiography; D004594:Electrophysiology / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000473:pathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D015424:Reperfusion; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology*