Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion
Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion
复制标题
DOI：
10.1161/01.res.0000151843.79801.60
复制
发表时间：
2005-01-07
影响因子：
20.1
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Kajstura, J;Rota, M;Anversa, P
最近在小鼠身上的研究挑战了骨髓细胞(BMC)分化为心肌细胞和冠状动脉的能力。也有人声称，BMCs只有通过与常驻细胞融合才能获得不同于血系的细胞表型。在诱导心肌梗死和成功地在小鼠心脏内注射骨髓细胞方面存在技术问题。同样，对死亡组织再生所涉及的细胞群的准确分析也很复杂，这些因素加在一起可能会解释否定的发现。在这项研究中，我们实施了一种易于复制的简单方案，并重新评估了注射BMCs是否能恢复小鼠心肌梗死，以及细胞融合是否参与了组织重建。为此，从表达增强型绿色荧光蛋白(EGFP)的雄性转基因小鼠中获得了c-kit阳性的骨髓细胞。用绿色荧光蛋白和Y染色体作为受体心脏移植细胞后代的标记。通过这种方法，我们已经证明，当在梗塞的心脏中适当地给予BMCs时，可以有效地分化为心肌细胞和冠状动脉，而不会检测到分化为造血系。然而，BMCs对存活心肌的生长行为没有明显的旁分泌作用。在脑梗塞内，10天内，独立于细胞融合，产生了近450万个生化和形态分化的心肌细胞，以及冠状小动脉和毛细血管结构。综上所述，骨髓细胞采用心肌细胞系，对缺血性心力衰竭有重要的治疗作用。
Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit-positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.