Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype.
BACKGROUND
Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefore sought to determine whether MSCs are present in the lungs of ovalbumin (OVA)-sensitized and challenged mice, a model of allergic airways disease.


METHODS
Balb/c mice were sensitized and challenged with PBS or OVA over a 25 day period. Flow cytometry as well as colony forming and differentiation potential were used to analyze the emergence of MSCs along with gene expression studies using immunochemical analyses, quantitative polymerase chain reaction (qPCR), and gene expression beadchips.


RESULTS
A CD45-negative subset of cells expressed Stro-1, Sca-1, CD73 and CD105. Selection for these markers and negative selection against CD45 yielded a population of cells capable of adipogenic, osteogenic and chondrogenic differentiation. Lungs from OVA-treated mice demonstrated a greater average colony forming unit-fibroblast (CFU-F) than control mice. Sorted cells differed from unsorted lung adherent cells, exhibiting a pattern of gene expression nearly identical to bone marrow-derived sorted cells. Finally, cells isolated from the bronchoalveolar lavage of a human asthma patient showed identical patterns of cell surface markers and differentiation potential.


CONCLUSIONS
In summary, allergen sensitization and challenge is accompanied by an increase of MSCs resident in the lungs that may regulate inflammatory and fibrotic responses.
Bentley
J Kelley
JK
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Popova
Antonia P
AP
Bozyk
Paul D
PD
Linn
Marisa J
MJ
Baek
Amy E
AE
Lei
Jing
J
Goldsmith
Adam M
AM
Hershenson
Marc B
MB
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D007114:Immunization / Q000379:methods; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D010047:Ovalbumin / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D010047:Ovalbumin