Dopamine mobilizes mesenchymal progenitor cells through D2-class receptors and their PI3K/AKT pathway

Stem Cells. 2014 Sep;32(9):2529-38. doi: 10.1002/stem.1745.

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.

Keywords: Catecholamines; Dopamine; Dopamine receptor; Mesenchymal progenitor cells; Mesenchymal stromal cells; Stem cell mobilization; Stem cell niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Dopamine / metabolism
  • Dopamine / pharmacology*
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, Dopamine / metabolism
  • Signal Transduction / drug effects

Substances

  • Receptors, Dopamine
  • Granulocyte Colony-Stimulating Factor
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Dopamine