Stem cell therapy enhances electrical viability in myocardial infarction

被引:91
作者
Mills, William R.
Mal, Niladri
Kiedrowski, Matthew J.
Unger, Ryan
Forudi, Farhad
Popovic, Zoran B.
Penn, Marc S.
Laurita, Kenneth R.
机构
[1] Case Western Reserve Univ, Heart & Vasc Res Ctr, Cleveland, OH 44109 USA
[2] Dept Cell Biol, Cleveland, OH 44109 USA
[3] Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44109 USA
[4] Ctr Stem Cell & Regenerat Med, Cleveland, OH 44109 USA
关键词
arrhythmia; electrophysiology; heart failure; skeletal myoblasts; mesenchymal stem cells;
D O I
10.1016/j.yjmcc.2006.09.011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Clinical studies suggest increased arrhythmia risk associated with cell therapy for myocardial infarction (MI); however, the underlying mechanisms are poorly understood. We hypothesize that the degree of electrical viability in the infarct and border zone associated with skeletal myoblast (SKMB) or mesenchymal stem cell (MSC) therapy will determine arrhythmia vulnerability in the whole heart. Within 24 h of LAD ligation in rats, 2 million intramyocardially injected SKMB (n=6), intravenously infused MSC (n=7), or saline (n=7) was administered. One month after MI, cardiac function was determined and novei optical mapping techniques were used to assess electrical viability and arrhythmia inducibility. Shortening fraction was greater in rats receiving SKMB (17.8% +/- 5.3%, p=0.05) or MSC (17.6% +/- 3.0%, p < 0.01) compared to MI alone (10.1% +/- 2.2%). Arrhythmia inducibility score was significantly greater in SKMB (2.8 +/- 0.2) compared to MI (1.4 +/- 0.5, p=0.05). Inducibility score for MSC (0.6 +/- 0.4) was significantly lower than SKMB (p=0.01) and tended to be lower than MI. Optical mapping revealed that MSC therapy preserved electrical viability and impulse propagation in the border zone, but SKMB did not. In addition, injected SKMBs were localized to discrete cell clusters where connexin expression was absent. In contrast, infused MSCs engrafted in a more homogeneous pattern and expressed connexin proteins. Even though both MSC and SKMB therapy improved cardiac function following MI in rat, SKMB therapy significantly increased arrhythmia inducibility while MSC therapy tended to lower inducibility. In addition, only MSC therapy was associated with enhanced electrical viability, diffuse engraftment, and connexin expression, which may explain the differences in arrhythmia inducibility. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:304 / 314
页数:11
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