Cord blood cell therapy alters LV remodeling and cytokine expression but does not improve heart function after myocardial infarction in rats

被引:8
|
作者
Rabald, Steffen [1 ]
Marx, Grit [2 ]
Mix, Brigitte [2 ]
Stephani, Caspar [3 ]
Kamprad, Manja [4 ]
Cross, Michael [5 ]
Boltze, Johannes [6 ]
Briest, Wilfried [7 ]
Zimmer, Heinz-Gerd [2 ]
Deten, Alexander [6 ,8 ]
机构
[1] Univ Leipzig, Dept Surg, Leipzig, Germany
[2] Univ Leipzig, Carl Ludwig Inst Physiol, Leipzig, Germany
[3] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany
[4] Univ Leipzig, Max Burger Res Ctr, Inst Immunol & Transfus Med, Leipzig, Germany
[5] Univ Leipzig, Dept Hematol Oncol, Leipzig, Germany
[6] Fraunhofer Inst Cell Therapy & Immunol, D-04103 Leipzig, Germany
[7] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA
[8] Univ Zurich, Vetsuisse Fac, Inst Vet Physiol, CH-8006 Zurich, Switzerland
关键词
myocardial infarction; heart function; remodeling; cell therapy; animal model;
D O I
10.1159/000129632
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective: In this study the ability of unrestricted somatic stem cells (USSC) and mononuclear cord blood cells (MN-CBC) was tested to improve heart function and left ventricular (LV) remodeling after myocardial infarction (MI). Methods: The cells were delivered by i.v. or intramyocardial injections in rat models of MI by permanent coronary artery occlusion and by ischemia/reperfusion (I/R) injury. Heart function and remodeling was followed by recurrent echocardiography over 8 or 12 weeks after which catheterization was performed. Results: Although injected labeled cells could be observed within the myocardium for up to 6 d, there was no sign of cardiac regeneration 8 or 12 weeks after MI. However, the mRNA expression of components of the extracellular matrix was attenuated in the infarct scar 12 weeks after MI and cell injection. Additionally, the expression of interleukin (IL)-6 but not of IL-1 beta increased at the site of injury and the adjacent border-zone 12 weeks after I/R and USSC-injection. However, these effects did not translate into improved heart function or attenuated LV dilatation. Conclusion: These data indicate that cord blood cell implantation after MI acts through paracrine mechanisms to modify remodeling rather than myocyte regeneration. The role of myofibroblasts and the optimal conditions of cell application need to be determined to translate these mechanisms into functional improvement. Copyright (C) 2008 S. Karger AG, Basel.
引用
收藏
页码:395 / 408
页数:14
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