Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells

Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells
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DOI:
10.1161/01.res.0000109792.43271.47
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发表时间:
2004-02-06
影响因子:
20.1
通讯作者:
Casteilla, L
Casteilla, L
中科院分区:
医学1区
文献类型:
--
作者:
Planat-Bénard, V;Menard, C;Casteilla, L

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心肌细胞再生在成人生活中是有限的。因此,鉴定一种假定的心肌细胞祖细胞来源对于提供一种可用的体外模型和再生治疗的新视角具有重要意义。由于脂肪组织最近被证明含有多能干细胞,因此研究了脂肪来源细胞的心肌细胞表型的出现。我们证明,在不添加5-氮杂胞苷的情况下,脂肪基质细胞培养后可以鉴定出具有心肌细胞特征的罕见跳动细胞。心肌细胞表型首先通过形态学观察确定,通过特定心脏标志物的表达、免疫细胞化学染色和超微结构分析证实,显示心室和心房样细胞的存在。在早期培养中进行的电生理研究显示细胞具有起搏器活性。最后,功能研究表明,肾上腺素能激动剂刺激心率,而胆碱能激动剂降低心率。综上所述,本研究表明,功能性心肌细胞样细胞可以直接从脂肪组织中获得。根据该组织在成年哺乳动物体内的大量存在,它可能是心肌细胞祖细胞的有用来源。
Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocytochemistry staining, and ultrastructural analysis, revealing the presence of ventricle- and atrial-like cells. Electrophysiological studies performed on early culture revealed a pacemaker activity of the cells. Finally, functional studies showed that adrenergic agonist stimulated the beating rate whereas cholinergic agonist decreased it. Taken together, this study demonstrated that functional cardiomyocyte-like cells could be directly obtained from adipose tissue. According to the large amount of this tissue in adult mammal, it could represent a useful source of cardiomyocyte progenitors.