title: Biodistribution of in vitro-derived microglia applied intranasally and intravenously to mice: effects of aging.
abstract: OBJECTIVE
  The age of both the donor and the recipient has a potential influence on the efficacy of various cell therapies, but the underlying mechanisms are still being charted. We studied the effect of donor and recipient age in the context of microglia migration.
  
  
  METHODS
  Microglia were in vitro--differentiated from bone marrow of young (3 months) and aged (12 months) mice and transplanted into young (∼ 3 months) and aged (∼ 17 months) C57BL/6 mice (n = 25) through intravenous and intranasal application routes. Recipients were not immune-suppressed or irradiated. Transplanted microglia were tracked through the use of a sex-mismatched setup or histologically with the use of cells from enhanced green fluorescent protein enhanced green fluorescent protein transgenic mice.
  
  
  RESULTS
  No acute rejections or transplant-associated toxicity was observed. After 10 days, both intravenously and intranasally transplanted cells were detected in the brain. Transplanted cells were also found in the blood and the lymph system. The applied cells were also tracked in lungs and kidney but only after intravenous injection subjected to a "pulmonary first-pass effect." After 28 days, intravenously delivered cells were also found in the bone marrow and other organs, especially in aged recipients. Whereas in young recipients the transplanted microglia did not appear to persist, in aged brains the transplanted cells could still be identified up to 28 days after transplantation. However, when cells from aged donors were used, no signals of transplanted cells could be detected in the recipients.
  
  
  CONCLUSIONS
  This study establishes proof of principle that in vitro--derived microglia from young but not from aged donors, intravenously or intranasally transplanted, migrate to the brain in young and aged recipients.
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Leovsky
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany; Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Fabian
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany; Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
authors.forename: Yahaira
authors.initials: Y
authors.lastname: Naaldijk
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Jäger
authors.affiliation: Korea Ministry of Food and Drug Safety (MFDS), Hangul, Korea.
authors.forename: Hwa Jin
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Böhme
authors.affiliation: Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rudolph
authors.affiliation: Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany; University of Loughborough, Centre for Biological Engineering, Wolfson School of Material and Manufacturing Engineering, Loughborough, United Kingdom. Electronic address: A.Stolzing@lboro.ac.uk.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stolzing
mesh_terms: D000281:Administration, Intranasal; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D049452:Green Fluorescent Proteins / Q000378:metabolism / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000637:transplantation*; D014018:Tissue Distribution
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: aging; biodistribution; cell tracking; intranasal; intravenous; microglia