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Blood, 1 July 2005, Vol. 106, No. 1, pp. 59-66.
Prepublished online as a Blood First Edition Paper on March 8, 2005; DOI 10.1182/blood-2004-09-3645.
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Submitted September 20, 2004
Accepted February 26, 2005
HB-EGF/HER -1 signalling in bone marrow mesenchymal stem cells: inducing cell expansion and preventing reversibly multi-lineage differentiation
Mauro Krampera*, Annalisa Pasini, Antonella Rigo, Maria T Scupoli, Cristina Tecchio, Giorgio Malpeli, Aldo Scarpa, Francesco Dazzi, Giovanni Pizzolo, and Fabrizio Vinante
Department of Clinical and Experimental Medicine, Section of Haematology, Verona, Italy
Department of Pathology, Section of Pathological Anatomy, Verona, Italy
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
* Corresponding author; email: mauro.krampera{at}univr.it.
Epidermal growth factor receptor-1 (EGFR-1/HER-1/ErbB) regulates proliferation and cell fate during epidermal development. HER-1 is activated by several EGF-family ligands including heparin-binding epidermal growth factor-like growth factor (HB-EGF), a mitogenic and chemotactic molecule that participates to tissue repair, tumour growth and other tissue-modelling phenomena, such as angiogenesis and fibrogenesis. We found that mesenchymal stem cells (MSC), the precursors of different mesenchymal tissues with a role in processes in which HB-EGF is often involved, normally express HER-1, but not HB-EGF itself. Under the effect of HB-EGF MSC proliferate more rapidly and persistently, without undergoing spontaneous differentiation. This effect occurs in a dose-dependent fashion, and is specific, direct, and HER-1-mediated, as it is inhibited by anti-HER-1 and anti-HB-EGF blocking antibodies. Moreover, HB-EGF reversibly prevents adipogenic, osteogenic and chondrogenic differentiation induced with specific media. These data show that HB-EGF/HER-1 signalling is relevant to MSC biology, by regulating both proliferation and differentiation.
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