title: Dopamine mobilizes mesenchymal progenitor cells through D2-class receptors and their PI3K/AKT pathway.
abstract: As the nervous system exerts direct and indirect effects on stem cells mobilization and catecholamines mobilize hematopoietic stem cells, we hypothesized that dopamine might induce mesenchymal progenitor cells (MPCs) mobilization. We show that dopamine induced in vitro MPCs migration through D2-class receptors, and their alternative phosphoinositide 3-kinase/Akt pathways. Also, administration of catecholamines induced in vivo mobilization of colony-forming unit-fibroblast in mice. In contrast, in vitro and in vivo MPCs migration was suppressed by D2-class receptors antagonists and blocking antibodies, consistent with dopamine signaling pathway implication. In humans, patients treated with L-dopa or catecholaminergic agonists showed a significant increase of a MPC-like population (CD45-CD31-CD34-CD105+) in their peripheral blood. These findings reveal a new link between catecholamines and MPCs mobilization and suggest the potential use of D2-class receptors agonists for mobilization of MPCs in clinical settings.
authors.affiliation: Unidad de Biotecnología Celular, ISCIII, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Mirones
authors.forename: Miguel
authors.initials: M
authors.lastname: Angel Rodríguez-Milla
authors.forename: Isabel
authors.initials: I
authors.lastname: Cubillo
authors.forename: Luis
authors.initials: L
authors.lastname: Mariñas-Pardo
authors.forename: Teresa
authors.initials: T
authors.lastname: de la Cueva
authors.forename: Agustín
authors.initials: A
authors.lastname: Zapata
authors.forename: Carlos
authors.initials: C
authors.lastname: González
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramírez
authors.forename: Javier
authors.initials: J
authors.lastname: García-Castro
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011954:Receptors, Dopamine; D016179:Granulocyte Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine
keywords: Catecholamines; Dopamine; Dopamine receptor; Mesenchymal progenitor cells; Mesenchymal stromal cells; Stem cell mobilization; Stem cell niche