title: Co-culture of hematopoietic stem cells with mesenchymal stem cells increases VCAM-1-dependent migration of primitive hematopoietic stem cells.
abstract: Hematopoietic stem cells (HSC) lose their capacity for engraftment during ex vivo cytokine expansion. It has been shown that mesenchymal stem cells (MSC) improve HSC transplantability; however, the molecular mechanisms responsible for this effect have not yet been completely elucidated. This paper reports that expanding HSC in co-culture with MSC enhances a vascular cell adhesion molecule (VCAM-1)-dependent pro-migratory phenotype. MSC did not regulate the HSC expression of CD49d (VCAM-1 counter-receptor molecule), but did decrease the cytokine-induced HSC VCAM-1-mediated pro-adhesive phenotype. Co-culture with MSC reduced the expression of the inactive conformation of lymphocyte function-associated antigen (LFA-1) at the HSC uropod, and induced higher expression of an LFA-1 activation epitope. Interestingly, VCAM-1-dependent HSC migration was modulated by targeting this LFA-1 high affinity form, suggesting integrin cross-regulation. VCAM-1-mediated HSC transmigration appeared to favor the more primitive HSC immunophenotype. Our results suggested that co-culture with MSC improved VCAM-1-dependent migration of primitive HSC, which was affected in ex vivo cytokine-expanded HSCs by a mechanism involving LFA-1 modulation.
authors: Cellular and Molecular Physiology Group, Physiology Division, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, DC, Colombia. anamperdomoa@unal.edu.co
authors: Ana-María
authors: AM
authors: Perdomo-Arciniegas
authors: Jean-Paul
authors: JP
authors: Vernot
mesh_terms: D040881:CD11a Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D040881:CD11a Antigen; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1