Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction

被引:218
作者
Mueller-Ehmsen, Jochen
Krausgrill, Benjamin
Burst, Volker
Schenk, Kerstin
Neisen, Uta C.
Fries, Jochen W. U.
Fleischmann, Bernd K.
Hescheler, Juergen
Schwinger, Robert H. G.
机构
[1] Univ Cologne, Dept Internal Med 3, Lab Muscle Res & Mol Cardiol, D-50937 Cologne, Germany
[2] Univ Cologne, Dept Internal Med 4, D-50937 Cologne, Germany
[3] Univ Cologne, Inst Pathol, D-50937 Cologne, Germany
[4] Univ Bonn, Inst Physiol 1, D-5300 Bonn, Germany
[5] Univ Cologne, Inst Neurophysiol, D-50937 Cologne, Germany
关键词
myocardial infarction; cell therapy; stem cells; transplantation; cell differentiation; bone marrow cells; mononuclear; mesenchymal;
D O I
10.1016/j.yjmcc.2006.07.023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Bone marrow cells are used with promising results for cell therapy after myocardial infarction (MI). We determined the survival and organ distribution of transplanted mononuclear (MNC) or mesenchymal (MSC) bone marrow cells, and the influence of cell type, cell number and application time. MNC and MSC (male Fischer 344 rats) were injected into the border zone of MI (syngeneic females) immediately or 7 days after LAD ligation (10(5) or 10(6) cells, 50 mu l). After 0 h, 48 h, 5 days, 3 weeks and 6 weeks, DNA of heart, lung, liver, spleen, kidney, blood, bone marrow, brain and skeletal muscle was isolated and the number of donor cells determined by quantitative real-time PCR with Y-chromosome specific primers (each n >= 4). The percentage of donor-cells in the heart decreased rapidly from 34-80% of injected cells (0 h) to 0.3-3.5% (6 weeks) independent from cell type, number and application time. The absolute number increased after increasing injected cell number (106 VS. 105). In the lung, MNC and MSC were found at 0 h (126 48 and 140 3 per million organ cells), but in liver and kidney, only few. At 48 h and 6 weeks, an increasing number of MNC, but not MSC, were detected in the spleen (6 weeks, 602 +/- 173 per million organ cells vs. 95 50 in the heart, P = 0.02). In all other organs, only few or no grafted cells of either cell type were detected at these times. Organ distribution was independent from injection time. The low survival of grafted cells may limit their therapeutic impact, while their distribution to other organs must be considered in all cell therapy applications. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:876 / 884
页数:9
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