Partial cell fusion:: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts
Partial cell fusion:: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts
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DOI：
10.1016/j.cardiores.2005.05.020
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发表时间：
2005-10-01
影响因子：
10.8
通讯作者：
Ramaekers, FCS
中科院分区：
文献类型：
--
作者：
Driesen, RB;Dispersyn, GD;Ramaekers, FCS
目的：在异种细胞培养中，成纤维细胞通过功能性缝隙连接与新生心肌细胞偶联。我们的目的是提供证据的成纤维细胞和成年心肌细胞在体外和体内的一个额外的类型的异源细胞之间的通信。方法：在异源细胞共培养的接触面积进行了评估，通过特定的标记和细胞间的通信进行了研究，使用预加载的成纤维细胞与示踪分子。异质细胞成纤维细胞-心肌细胞接触存在于体外环境中，并在边界区的兔心肌梗死在体内进行了进一步检查，通过电子microscopic.Results：此外，成纤维细胞预载荧光低分子量示踪剂钙黄绿素-AM培养的心肌细胞表明早期染料转移通过连接蛋白43功能间隙连接。在共培养后的稍后时间段，预装载有高分子量示踪剂葡聚糖10，000的成纤维细胞的染料转移表明部分细胞融合。通过电子显微镜证实了引起这种部分细胞融合的膜连续性，清楚地显示了成纤维细胞和表型适应（去分化）心肌细胞之间的胞质间接触区域。黄绿素标记的膜联蛋白V的亲和力研究表明，接触部位的磷脂酰丝氨酸的短暂暴露，表明磷脂酰丝氨酸介导的融合过程。心脏成纤维细胞和去分化的心肌细胞之间的密切联系，伴随着破坏的基底层观察在边界区的兔myocardial infarction in vivo.Conclusion：我们的研究结果表明，部分细胞融合型的异源细胞通信在我们的共培养模型和在体内观察到的接触，可能会导致新的见解，在心血管疾病。(c)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Fibroblasts have been shown to couple to neonatal cardiomyocytes in heterocellular cultures through functional gap junctions. Our objective was to provide evidence for an additional type of heterocellular communication between fibroblasts and adult cardiomyocytes in vitro and in vivo.Methods: The contact areas in heterocellular co-cultures were evaluated by specific labeling and the intercellular communication was studied using preloading of fibroblasts with tracer molecules. Heterocellular fibroblast-cardiomyocyte contacts present in the in vitro setting and in the border zone of a rabbit myocardial infarction in vivo were further examined by electron microscopy.Results: Addition of fibroblasts preloaded with the fluorescent low molecular weight tracer calcein-AM to cultured myocytes indicated early dye transfer via connexin 43 functional gap junctions. At a later time-period after co-culturing, dye transfer of fibroblasts preloaded with the high molecular weight tracer dextran 10,000 suggested partial cell fusion. The membrane continuity giving rise to this partial cell fusion was confirmed by electron microscopy, clearly showing areas of intercytoplasmic contacts between fibroblasts and phenotypically adapted (dedifferentiated) cardiomyocytes. Fluorescein-labeled annexin V affinity studies revealed transient exposure of phosphatidylserine at the contact sites, suggesting that phosphatidylserine mediates the fusion process. Close contacts between cardiac fibroblasts and dedifferentiated cardiomyocytes accompanied by disruption of the basal lamina were observed in the border zone of a rabbit myocardial infarction in vivo.Conclusion: Our results suggest that the partial cell fusion-type of heterocellular communication in our co-culture model and the contacts observed in vivo may lead to new insights in cardiovascular disease. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.