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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3438-3446.
Prepublished online as a Blood First Edition Paper on May 24, 2007; DOI 10.1182/blood-2006-11-055566.


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STEM CELLS IN HEMATOLOGY

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

Antonio P. Beltrami1, Daniela Cesselli1, Natascha Bergamin1, Patrizia Marcon1, Silvia Rigo1, Elisa Puppato1, Federica D'Aurizio1, Roberto Verardo2, Silvano Piazza2, Angela Pignatelli3, Alessandra Poz1, Umberto Baccarani1, Daniela Damiani1, Renato Fanin1, Laura Mariuzzi1, Nicoletta Finato1, Paola Masolini1, Silvia Burelli1, Ottorino Belluzzi3, Claudio Schneider2, and Carlo A. Beltrami1

1 Centro Interdipartimentale Medicina Rigenerativa (CIME), University of Udine, Udine; 2 Laboratorio Internazionale Consorzio Interuniversitario Biotecnologie (LNCIB), Trieste; and 3 Dipartimento Biologia, Sezione di Fisiologia e Biofisica–Centro di Neuroscienze, Universita di Ferrara, Ferrara, Italy

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.


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