Kajstura Jan, Rota Marcello, Whang Brian, Cascapera Stefano, Hosoda Toru, Bearzi Claudia, Nurzynska Daria, Kasahara Hideko, Zias Elias, Bonafé Massimiliano, Nadal-Ginard Bernardo, Torella Daniele, Nascimbene Angelo, Quaini Federico, Urbanek Konrad, Leri Annarosa, Anversa Piero
Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Circ Res. 2005 Jan 7;96(1):127-37. doi: 10.1161/01.RES.0000151843.79801.60. Epub 2004 Nov 29.
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.
最近在小鼠身上进行的研究对骨髓细胞（BMCs）分化为心肌细胞和冠状血管的能力提出了挑战。还有人声称，BMCs只有通过与驻留细胞融合才能获得不同于血细胞谱系的细胞表型。在小鼠心脏中诱导心肌梗死以及成功注射BMCs存在技术问题。同样，对参与坏死组织再生的细胞群体进行准确分析也很复杂，这些因素共同可能导致了阴性结果。在本研究中，我们实施了一个易于重复的简单方案，并重新评估了注射BMCs是否能恢复小鼠梗死心肌，以及细胞融合是否参与组织重构。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取c-kit阳性BMCs。EGFP和Y染色体被用作受体心脏中移植细胞后代的标记。通过这种方法，我们证明了BMCs在梗死心脏中适当给药时，能有效地分化为心肌细胞和冠状血管，而未检测到向造血谱系的分化。然而，BMCs对存活心肌的生长行为没有明显的旁分泌作用。在梗死区内，10天内独立于细胞融合产生了近450万个生化和形态上分化的心肌细胞以及冠状动脉小动脉和毛细血管结构。总之，BMCs采用心脏细胞谱系，对缺血性心力衰竭具有重要的治疗作用。
