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

Abstract

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. (Blood. 2005;106:59-66)

Regulation of cell proliferation by intermediate-conductance Ca2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells

“…3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was applied to assess the effects of ion channel blockers on cell proliferation (19). Mouse MSCs were plated into 96-well plates at a density of 5 ϫ 10 4 cells per well in 200 l complete culture medium.…”

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

“…71 Another pathway involved in pericyte recruitment is through heparin-binding epidermal growth factor (HB-EGF). 72 HB-EGF, implicated in cardiovascular development, has also been found to have protective effect on pericytes by supporting pericyte proliferation and minimizing the effects anoxiainduced apoptosis. 73 Several studies have demonstrated that HB-EGF pathways may experience crosstalk with PDGF pathways.…”

Tethered Epidermal Growth Factor Provides a Survival Advantage to Mesenchymal Stem Cells

“…These signals promote migration, adhesion, proliferation, and survival in various cell types [13,15,16]. Both EGFR expression and EGF responsiveness have been reported in marrow-derived MSC [17][18][19][20][21]. We recently reported that stimulation of MSC with soluble EGF induces EGFR signaling and promotes MSC proliferation and migration without affecting pluripotency [18].…”