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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, CD105Lo immunophenotype and were bipotent, lacking adipogenic potential. In contrast, MSCs were readily recoverable from healthy human lung tissue and were CD90Hi or Lo, CD73Hi, CD45Neg, CD105Int and 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 \u03b1-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.<\/jats:p>","DOI":"10.1002\/stem.2419","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T09:38:10Z","timestamp":1467193090000},"page":"2548-2558","source":"Crossref","is-referenced-by-count":28,"title":["Mesenchymal Stromal Cells are Readily Recoverable from Lung Tissue, but not the Alveolar Space, in Healthy Humans"],"prefix":"10.1093","volume":"34","author":[{"given":"K. A.","family":"Sinclair","sequence":"first","affiliation":[{"name":"School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"},{"name":"Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. T.","family":"Yerkovich","sequence":"additional","affiliation":[{"name":"School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"},{"name":"Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Chen","sequence":"additional","affiliation":[{"name":"The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. L.","family":"McQualter","sequence":"additional","affiliation":[{"name":"Lung and Regenerative Medical Institutes, Cedars-Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. M-A.","family":"Hopkins","sequence":"additional","affiliation":[{"name":"School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"},{"name":"Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-3628","authenticated-orcid":false,"given":"C. A.","family":"Wells","sequence":"additional","affiliation":[{"name":"The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. C.","family":"Chambers","sequence":"additional","affiliation":[{"name":"School of Medicine, The Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"},{"name":"Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,7,4]]},"reference":[{"key":"2022010901420255000_stem2419-bib-0001","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nature09262","article-title":"Mesenchymal and haematopoietic stem cells form a unique bone marrow niche","volume":"466","author":"Mendez-Ferrer","year":"2010","journal-title":"Nature"},{"key":"2022010901420255000_stem2419-bib-0002","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1172\/JCI68782","article-title":"Type 2 alveolar cells are stem cells in adult lung","volume":"123","author":"Barkauskas","year":"2013","journal-title":"J Clin Investig"},{"key":"2022010901420255000_stem2419-bib-0003","doi-asserted-by":"crossref","first-page":"L829","DOI":"10.1152\/ajplung.00347.2011","article-title":"Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia","volume":"302","author":"Tropea","year":"2012","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2022010901420255000_stem2419-bib-0004","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1073\/pnas.0510511103","article-title":"Mitochondrial transfer between cells can rescue aerobic respiration","volume":"103","author":"Spees","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022010901420255000_stem2419-bib-0005","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nm.2736","article-title":"Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury","volume":"18","author":"Islam","year":"2012","journal-title":"Nat Med"},{"key":"2022010901420255000_stem2419-bib-0006","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/stem.604","article-title":"The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation","volume":"29","author":"Jun","year":"2011","journal-title":"Stem Cells"},{"key":"2022010901420255000_stem2419-bib-0007","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. 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