title: Aging mesenchymal stem cells fail to protect because of impaired migration and antiinflammatory response.
abstract: BACKGROUND
  Aging is characterized by functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. With age, there is an increase in the incidence and severity of chronic and acute lung diseases. However, the relationship between age and the lung's reduced ability to repair is far from established and necessitates further research in the field.
  
  
  OBJECTIVE
  Little is currently known about age-related phenomena in mesenchymal stem cells (MSCs). On account of their ability to protect the endothelium and the alveolar epithelium through multiple paracrine mechanisms, we looked for adverse effects that aging might cause in MSC biology. Such age-related changes might partly account for the increased susceptibility of the aging lung to injury.
  
  
  RESULTS
  We demonstrated that old mice have more inflammation in response to acute lung injury. To investigate the causes, we compared the global gene expression of aged and young bone marrow-derived MSCs (B-MSCs). Our results revealed that the expression levels of inflammatory response genes depended on the age of the B-MSCs. We demonstrated that the age-dependent decrease in expression of several cytokine and chemokine receptors is important for the migration and activation of B-MSCs. Finally, we showed by adoptive transfer of aged B-MSCs to young endotoxemic mice that aged cells lacked the antiinflammatory protective effect of their young counterparts.
  
  
  CONCLUSIONS
  Taken together, the decreased expression of cytokine and chemokine receptors in aged B-MSCs compromises their protective role by perturbing the potential of B-MSCs to become activated and mobilize to the site of injury.
authors.affiliation: 1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bustos
authors.forename: Luai
authors.initials: L
authors.lastname: Huleihel
authors.forename: Maria G
authors.initials: MG
authors.lastname: Kapetanaki
authors.forename: Christian L
authors.initials: CL
authors.lastname: Lino-Cardenas
authors.forename: Lyle
authors.initials: L
authors.lastname: Mroz
authors.forename: Bryon M
authors.initials: BM
authors.lastname: Ellis
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: McVerry
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Richards
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.forename: Nayra
authors.initials: N
authors.lastname: Cerdenes
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mora
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000503:physiopathology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000502:physiology
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines