title: Mesenchymal Stromal Cells are Readily Recoverable from Lung Tissue, but not the Alveolar Space, in Healthy Humans.
abstract: Stromal support is critical for lung homeostasis and the maintenance of an effective epithelial barrier. Despite this, previous studies have found a positive association between the number of mesenchymal stromal cells (MSCs) isolated from the alveolar compartment and human lung diseases associated with epithelial dysfunction. We hypothesised that bronchoalveolar lavage derived MSCs (BAL-MSCs) are dysfunctional and distinct from resident lung tissue MSCs (LT-MSCs). In this study, we comprehensively interrogated the phenotype and transcriptome of human BAL-MSCs and LT-MSCs. We found that MSCs were rarely recoverable from the alveolar space in healthy humans, but could be readily isolated from lung transplant recipients by bronchoalveolar lavage. BAL-MSCs exhibited a CD90Hi, CD73Hi, CD45Neg, CD105Loimmunophenotype and were bipotent, lacking adipogenic potential. In contrast, MSCs were readily recoverable from healthy human lung tissue and were CD90Hi or Lo, CD73Hi, CD45Neg, CD105Intand had full tri-lineage potential. Transcriptional profiling of the two populations confirmed their status as bona fide MSCs and revealed a high degree of similarity between each other and the archetypal bone-marrow MSC. 105 genes were differentially expressed; 76 of which were increased in BAL-MSCs including genes involved in fibroblast activation, extracellular matrix deposition and tissue remodelling. Finally, we found the fibroblast markers collagen 1A1 and α-smooth muscle actin were increased in BAL-MSCs. Our data suggests that in healthy humans, lung MSCs reside within the tissue, but in disease can differentiate to acquire a profibrotic phenotype and migrate from their in-tissue niche into the alveolar space. Stem Cells 2016;34:2548-2558.
authors.affiliation: School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia. kenneth.sinclair@uqconnect.edu.au.|Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia. kenneth.sinclair@uqconnect.edu.au.
authors.forename: K A
authors.initials: KA
authors.lastname: Sinclair
authors.affiliation: School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.|Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia.
authors.forename: S T
authors.initials: ST
authors.lastname: Yerkovich
authors.affiliation: The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.affiliation: Lung and Regenerative Medical Institutes, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: McQualter
authors.affiliation: School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.|Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia.
authors.forename: P M-A
authors.initials: PM
authors.lastname: Hopkins
authors.affiliation: The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: C A
authors.identifier: 0000-0003-3133-3628
authors.initials: CA
authors.lastname: Wells
authors.affiliation: School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.|Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia.
authors.forename: D C
authors.initials: DC
authors.lastname: Chambers
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D016000:Cluster Analysis; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D003114:Colony-Forming Units Assay; D000071063:Endoglin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000166:cytology*; D016040:Lung Transplantation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000166:cytology*; D059467:Transcriptome / Q000235:genetics; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D000071063:Endoglin
keywords: Lung; Mesenchymal stem cells; Mesenchymal stromal cells; Microarray; Transcriptome