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多能细胞可以在体外从几种成人器官(心脏、肝脏和骨髓)中生成。

Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow).

作者信息

Beltrami Antonio P, Cesselli Daniela, Bergamin Natascha, Marcon Patrizia, Rigo Silvia, Puppato Elisa, D'Aurizio Federica, Verardo Roberto, Piazza Silvano, Pignatelli Angela, Poz Alessandra, Baccarani Umberto, Damiani Daniela, Fanin Renato, Mariuzzi Laura, Finato Nicoletta, Masolini Paola, Burelli Silvia, Belluzzi Ottorino, Schneider Claudio, Beltrami Carlo A

机构信息

Centro Interdipartimentale Medicina Rigenerativa, University of Udine, Piazzale Santa Maria della Misericordia, 33100 Udine, Italy.

出版信息

Blood. 2007 Nov 1;110(9):3438-46. doi: 10.1182/blood-2006-11-055566. Epub 2007 May 24.

Abstract

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.

摘要

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生成一群在培养中表现为多能干细胞的细胞,以及这些细胞是否具有共同特性。为此,我们培养并克隆了从成人肝脏、心脏和骨髓获得的有限细胞系,并将它们命名为人类多能成体干细胞(hMASC)。从这3种不同组织获得的克隆hMASC表达多能状态特异性转录因子Oct-4、NANOG和REX1,显示出端粒酶活性,并在形态和功能水平上均表现出广泛的分化潜能。hMASC维持人类二倍体DNA含量,与几种体细胞系相比,无论分离组织如何,都具有共同的基因表达特征。特别是,调节干细胞自我更新/维持的信号通路,如Wnt、Hedgehog和Notch,在转录水平上具有活性。我们的研究结果表明,我们已经优化了一种体外方案,以从多个器官中生成和扩增细胞,这些细胞甚至可以被诱导获得与起源组织在胚胎学上无关的成熟细胞的形态和功能特征。

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