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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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HEMATOPOIESIS

HB-EGF/HER-1 signaling in bone marrow mesenchymal stem cells: inducing cell expansion and reversibly preventing multilineage differentiation

Mauro Krampera, Annalisa Pasini, Antonella Rigo, Maria Teresa Scupoli, Cristina Tecchio, Giorgio Malpeli, Aldo Scarpa, Francesco Dazzi, Giovanni Pizzolo, and Fabrizio Vinante

From the Department of Clinical and Experimental Medicine, Section of Haematology, and the Department of Pathology, Section of Pathological Anatomy, University of Verona, Italy; and the Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London.

Epidermal growth factor receptor-1 (EGFR-1/HER-1/ErbB-1) 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 in tissue repair, tumor growth, and other tissue-modeling phenomena, such as angiogenesis and fibrogenesis. We found that mesenchymal stem cells (MSCs), 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, MSCs 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 signaling is relevant to MSC biology, by regulating both proliferation and differentiation.


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