Reference : Modulation of homing properties of primitive progenitor cells generated by ex vivo ex...
Scientific journals : Article
Human health sciences : Hematology
Modulation of homing properties of primitive progenitor cells generated by ex vivo expansion.
Foguenne, Jacques [Université de Liège - ULiège > Département des sciences cliniques > Hématologie biologique >]
Huygen, Sandra [> > > >]
Greimers, Roland [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Beguin, Yves [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
Gothot, André mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie biologique et immuno hématologie >]
Ferrata Storti Foundation
Yes (verified by ORBi)
[en] Animals ; Antigens, CD/blood ; Bone Marrow ; Cell Adhesion Molecules/metabolism ; Cell Division ; Cell Movement ; Cells, Cultured ; Down-Regulation ; Fibronectins/metabolism ; Glycoproteins/blood ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology ; Integrin alpha4beta1/physiology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mitosis/physiology ; Peptides/blood ; Receptors, Lymphocyte Homing ; Vascular Cell Adhesion Molecule-1/metabolism
[en] BACKGROUND AND OBJECTIVES: The maintenance of adequate interactions with the bone marrow (BM) microenvironment is critical to ensure efficient homing of ex vivo-expanded hematopoietic cells. This study was intended to assess adhesion and migration properties of long-term culture-initiating cells (LTC-IC) harvested after self-renewal division in ex vivo culture and to determine their susceptibility to growth-inhibitory signals mediated by adhesion to BM stromal ligands. DESIGN AND METHODS: We used cell tracking to isolate primitive LTC-IC that had accomplished 1 or 2 divisions ex vivo. Adhesion, migration and growth inhibition of divided LTC-IC were determined in the presence of purified BM ligands, and compared to the properties of uncultured LTC-IC. RESULTS: As compared to undivided LTC-IC, adhesion and migration mediated by very late antigen (VLA)-4 integrin across both vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (Fn) were downregulated in post-mitotic LTC-IC. Conversely, binding and motility via VLA-5 across Fn were stimulated. No changes occurred in LTC-IC interactions with intercellular adhesion molecule-1 (ICAM-1) or with E- or P-selectin. Proliferation of uncultured LTC-IC was inhibited by VLA-4-mediated binding to VCAM-1 and the CS-1 domain of Fn, as well as binding to P-selectin. Growth of ex vivo-generated LTC-IC became unresponsive to these 3 ligands but was suppressed through VLA-5 engagement by the cell binding domain of Fn. INTERPRETATION AND CONCLUSIONS: The generation of LTC-IC in expansion culture is associated with functional alterations of adhesion receptors, modulating not only binding and migration in the BM but also responsiveness to adhesion-mediated growth inhibitory signals. Such changes may limit homing and engraftment of expanded primitive stem/progenitor cells.

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