Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.
The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100μL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI.
Department of Cardiovascular Medicine, Shinshu University, Matsumoto, Japan.
Milan
M
Gautam
Department of Anatomy and Organ Technology, Shinshu University, Matsumoto, Japan; Department of Biotechnology and Biomedical Engineering, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan.
Daiki
D
Fujita
Department of Cardiovascular Medicine, Shinshu University, Matsumoto, Japan.
Kazuhiro
K
Kimura
Department of Cardiovascular Medicine, Shinshu University, Matsumoto, Japan.
Hinako
H
Ichikawa
Department of Cardiovascular Medicine, Shinshu University, Matsumoto, Japan.
Atsushi
A
Izawa
Department of Molecular and Cellular Pharmacology, Iwate Medical University, Iwate, Japan.
Masamichi
M
Hirose
Molecular Pharmacology, Shinshu University, Matsumoto, Japan.
Toshihide
T
Kashihara
Molecular Pharmacology, Shinshu University, Matsumoto, Japan.
Mitsuhiko
M
Yamada
Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
Masafumi
M
Takahashi
Department of Cardiovascular Medicine, Shinshu University, Matsumoto, Japan.
Uichi
U
Ikeda
Department of Cardiovascular Medicine, Shinshu University, Matsumoto, Japan; Department of Biotechnology and Biomedical Engineering, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan. Electronic address: yshiba@shinshu-u.ac.jp.
Yuji
Y
Shiba
D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006329:Heart Conduction System; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013610:Tachycardia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014185:Transplantation, Isogeneic
Adipose-derived stem cells; Echocardiography; Myocardial infarction; Pro-survival cocktail; Programmed electrical stimulation; Ventricular tachyarrhythmia