Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype

Abstract

BackgroundRecent 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.MethodsBalb/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.ResultsA 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.ConclusionsIn summary, allergen sensitization and challenge is accompanied by an increase of MSCs resident in the lungs that may regulate inflammatory and fibrotic responses.

Proliferation modulates intestinal smooth muscle phenotype in vitro and in colitis in vivo

“…While not well understood, both smooth muscle hypertrophy and hyperplasia contribute to increased muscle mass in airway disease (1). A recent study of an airway sensitization and challenge model in mice found specific evidence for smooth muscle hypertrophy, measuring increases in SMC size that were comparable to those recorded here (2). Similar studies in rats showed decreased expression of key smooth muscle markers (21), implying that hypertrophy is associated with decreased density of expression in multiple systems.…”

Glycogen synthase kinase-3β/β-catenin signaling regulates neonatal lung mesenchymal stromal cell myofibroblastic differentiation

“…Slides were probed with FITC-or Cy3-labeled mouse anti-␣-smooth muscle actin (clone 1A4, Sigma-Aldrich), AlexaFluorconjugated rabbit anti-phospho-GSK-3␤/mouse anti-␤-catenin (Cell Signaling Technology, Beverly, MA), or rabbit anti-connective tissue growth factor (CTGF) (Abcam, Cambridge, MA). Primary antibodies were coupled to AlexaFluor dyes (Invitrogen, Carlsbad, CA) as described (5).…”

Resistin-Like Molecule α Stimulates Proliferation of Mesenchymal Stem Cells While Maintaining Their Multipotency

“…It is possible to speculate that resistin plays a significant role in bone marrow proliferation and homeostasis. Interestingly, Bentley et al [33] showed that the number of multipotent mesenchymal stromal cells increased in the lungs of mice subjected to an ovalbumin-induced asthma model. It is also known that RELMa expression is highly upregulated in mouse lungs when subjected to that asthma model [2].…”