Mesenchymal stromal cells isolated from bronchoalveolar lavage and digest parenchymal lung tissue

ABSTRACT: Stromal support is critical to the achievement of lung homeostasis and the maintenance of an effective epithelial barrier, and yet previous studies have found a positive association between the number of mesenchymal stromal cell populations (MSCs) isolated from the alveolar space and human diseases associated with epithelial dysfunctional. We hypothesised that alveolar MSCs (A-MSCs) represent a dysfunctional population which would be distinct from lung tissue MSCs (LT-MSCs) and which would not be recoverable from healthy humans. In this study, we comprehensively interrogated the phenotype and transcriptome of human A-MSCs and LT-MSCs. We found that MSCs were rarely recoverable from the alveolar space in healthy humans, but were readily isolated from lung transplant recipients, where they expressed a CD90Hi, CD73Hi, CD45Neg, CD105Lo immunophenotype and were bipotent, lacking adipogenic potential. In contrast, MSCs were readily recoverable from healthy lung tissue and were CD90Hi or Lo, CD73Hi, CD45Neg, CD105Int and had full tri-lineage potential. Transcriptome profiling of the two populations confirmed their status as MSCs and revealed a high degree of similarity between each other and the archetypal bone-marrow MSC. 105 genes were differentially expressed, with genes involved in fibroblast activation, extracellular matrix deposition and tissue remodelling being up-regulated in A-MSCs. Finally, we found the fibroblast markers collagen 1 and α-smooth muscle actin was increased in A-MSCs. Our data suggest that in healthy humans, lung MSCs reside within the tissue, but in disease can differentiate to acquire a profibrotic phenotype and so move out of their niche into the alveolar space. Total RNA obtained from in vitro expanded MSCs (p2-4)

ORGANISM(S): Homo sapiens

SUBMITTER: Tyrone Chen 

PROVIDER: E-GEOD-74284 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress