title: Differentiation of mouse bone marrow derived stem cells toward microglia-like cells.
abstract: BACKGROUND
  Microglia, the macrophages of the brain, have been implicated in the causes of neurodegenerative diseases and display a loss of function during aging. Throughout life, microglia are replenished by limited proliferation of resident microglial cells. Replenishment by bone marrow-derived progenitor cells is still under debate. In this context, we investigated the differentiation of mouse microglia from bone marrow (BM) stem cells. Furthermore, we looked at the effects of FMS-like tyrosine kinase 3 ligand (Flt3L), astrocyte-conditioned medium (ACM) and GM-CSF on the differentiation to microglia-like cells.
  
  
  METHODS
  We assessed in vitro-derived microglia differentiation by marker expression (CD11b/CD45, F4/80), but also for the first time for functional performance (phagocytosis, oxidative burst) and in situ migration into living brain tissue. Integration, survival and migration were assessed in organotypic brain slices.
  
  
  RESULTS
  The cells differentiated from mouse BM show function, markers and morphology of primary microglia and migrate into living brain tissue. Flt3L displays a negative effect on differentiation while GM-CSF enhances differentiation.
  
  
  CONCLUSIONS
  We conclude that in vitro-derived microglia are the phenotypic and functional equivalents to primary microglia and could be used in cell therapy.
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Perlickstrasse 1, 04103, Leipzig, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Hinze
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stolzing
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000473:pathology* / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D013234:Stem Cells / Q000473:pathology; D051941:fms-Like Tyrosine Kinase 3 / Q000494:pharmacology
chemical_list: D000943:Antigens, Differentiation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3