Analysis of the origin and population dynamics of cardiac progenitor cells in a donor heart model
Analysis of the origin and population dynamics of cardiac progenitor cells in a donor heart model
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DOI：
10.1634/stemcells.2006-0497
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Li, Tao-Sheng;Suzuki, Ryo;Hamano, Kimikazu
最近在新生和成年小鼠、大鼠和人类的心肌中检测到并分离出了心脏祖细胞（干细胞）；然而，这些细胞的确切起源和特征仍然不清楚。利用异位小鼠心脏移植模型，我们研究了心脏祖细胞的来源和种群动态。将野生型C57/BL6雌性小鼠供体心脏移植到绿色荧光蛋白（GFP）转基因C57/BL6雄性小鼠体内。分别于移植后0、2、4、8、12周收集供体心脏。我们使用定量流式细胞术分析供体心脏中干细胞的数量和来源，并使用免疫染色来评估其特征的时间相关变化。心外gfp阳性干细胞在移植后很快迁移到供体心脏。免疫染色显示，这些gfp阳性干细胞在供体心脏中逐渐失去造血标志物CD45和CD34的表达，转而表达心脏特异性转录因子gta4和NKx2.5。在没有与供体心肌细胞融合的情况下，供体心脏中少数gfp阳性细胞最终获得成熟的心脏表型。我们的发现提供了第一个证据，表明心外干细胞可能来自骨髓，它们可以根据心肌环境信号转化为心脏祖细胞。
Cardiac progenitor (stem) cells have recently been detected in and isolated from the myocardium of neonatal and adult mice, rats, and humans; however, the precise origin and characterization of these cells remain unclear. Using a heterotopic mouse heart transplantation model, we investigated the origin and population dynamics of cardiac progenitor cells. Donor hearts from wild-type C57/BL6 female mice were transplanted into green fluorescent protein (GFP)-transgenic C57/BL6 male mice. The donor hearts were collected 0, 2, 4, 8, and 12 weeks after transplantation. We used quantitative flow cytometry to analyze the number and origin of stem cells in the donor hearts and immunostaining to evaluate the time-related changes in their characteristics. Extracardiac GFP-positive stem cells immigrated into the donor hearts soon after transplantation. Immunostaining revealed that these GFP-positive stem cells in the donor hearts gradually lost expression of the hematopoietic markers of CD45 and CD34 and shifted to express the cardiac-specific transcription factors GATA-4 and NKx2.5. A few of the GFP-positive cells in the donor hearts finally acquired the mature cardiac phenotype in the absence of cell fusion with donor cardiomyocytes. Our discovery provides the first evidence that extracardiac stem cells may be of bone marrow origin, from which they can transform into cardiac progenitor cells in response to myocardial environment cues.