Müller-Ehmsen Jochen, Krausgrill Benjamin, Burst Volker, Schenk Kerstin, Neisen Uta C, Fries Jochen W U, Fleischmann Bernd K, Hescheler Jürgen, Schwinger Robert H G
Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Kerpener Str. 62, 50937 Köln, Germany.
J Mol Cell Cardiol. 2006 Nov;41(5):876-84. doi: 10.1016/j.yjmcc.2006.07.023. Epub 2006 Sep 14.
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 microl). 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>or=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 (10(6) vs. 10(5)). 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.
骨髓细胞用于心肌梗死（MI）后的细胞治疗，效果良好。我们测定了移植的单核（MNC）或间充质（MSC）骨髓细胞的存活情况和器官分布，以及细胞类型、细胞数量和应用时间的影响。将MNC和MSC（雄性Fischer 344大鼠）在结扎左前降支（LAD）后立即或7天注射到MI的边缘区（同基因雌性）（10⁵或10⁶个细胞，50微升）。在0小时、48小时、5天、3周和6周后，分离心脏、肺、肝、脾、肾、血液、骨髓、脑和骨骼肌的DNA，并用Y染色体特异性引物通过定量实时PCR测定供体细胞数量（每组n≥4）。心脏中供体细胞的百分比迅速从注射细胞的34 - 80%（0小时）降至0.3 - 3.5%（6周），与细胞类型、数量和应用时间无关。随着注射细胞数量增加（10⁶对10⁵），绝对数量增加。在肺中，0小时时发现了MNC和MSC（每百万器官细胞分别为126±48和140±3），但在肝和肾中很少。在48小时和6周时，脾脏中检测到的MNC数量增加，但MSC没有（6周时，每百万器官细胞为602±173，而心脏中为95±50，P = 0.02）。在这些时间点，在所有其他器官中，两种细胞类型的移植细胞都很少或未检测到。器官分布与注射时间无关。移植细胞的低存活率可能会限制其治疗效果，而在所有细胞治疗应用中都必须考虑它们向其他器官的分布。
