Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow)
Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow)
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DOI：
10.1182/blood-2006-11-055566
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发表时间：
2007-11-01
期刊：
影响因子：
20.3
通讯作者：
Beltrami, Carlo A.
中科院分区：
文献类型：
--
作者：
Beltrami, Antonio R.;Cesselli, Daniela;Beltrami, Carlo A.
我们研究的目的是验证是否有可能在体外从不同的成人组织中产生一群细胞，这些细胞在培养中表现为多能干细胞，以及这些细胞是否具有共同的特性。为此，我们生长和克隆了从成人肝脏、心脏和骨髓中获得的有限细胞系，并将其命名为人多能成体干细胞（hMASC）。从3种不同组织中获得的克隆hMASCs表达多能状态特异性转录因子Oct-4、NANOG和REX 1，显示端粒酶活性，并表现出广泛的分化潜能，如在形态和功能水平上所示。与几种体细胞系相比，hMASCs保持了人二倍体DNA含量，并共享了共同的基因表达特征，与分离的组织无关。特别是，调节干细胞自我更新/维持的途径，如Wnt，Hedgehog和Notch，是转录活性的。我们的研究结果表明，我们已经优化了一种体外方案，以产生和扩增来自多个器官的细胞，这些细胞可以被诱导获得成熟细胞的形态和功能特征，甚至在胚胎学上与起源组织无关。
The aims of our study were to verify whether it was possible to generate in vitro, from different adult human tissues, a population of cells that behaved, in culture, as multipotent stem cells and if these latter shared common properties. To this purpose, we grew and cloned finite cell lines obtained from adult human liver, heart, and bone marrow and named them human multipotent adult stem cells (hMASCs). Cloned hMASCs, obtained from the 3 different tissues, expressed the pluripotent state-specific transcription factors Oct-4, NANOG, and REX1, displayed telomerase activity, and exhibited a wide range of differentiation potential, as shown both at a morphologic and functional level. hMASCs maintained a human diploid DNA content, and shared a common gene expression signature, compared with several somatic cell lines and irrespectively of the tissue of isolation. In particular, the pathways regulating stem cell self-renewal/maintenance, such as Wnt, Hedgehog, and Notch, were transcriptionally active. Our findings demonstrate that we have optimized an in vitro protocol to generate and expand cells from multiple organs that could be induced to acquire morphologic and functional features of mature cells even embryologically not related to the tissue of origin.