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Functional tissue specific MSC in lung-transplanted patients with and without bronchiolitis obliterans syndrome (BOS) - a potential source for cell-therapy?

ABSTRACT: Background: Mesenchymal stromal cells (MSC) have been proposed as a future cell based therapy for lung diseases like bronchiolitis obliterans syndrome (BOS). Theoretically, it might be beneficial to use lung resident MSC already adapted to the pulmonary environment. We therefore aimed to compare lung MSC with the well-characterized bone marrow MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to MSC isolated from good outcome recipients. Methods: MSC were isolated from bone marrow (BM) and adult/fetal lung tissues and compared by a comprehensive panel of assays. Results:The gene expression profiles of adult lung derived and fetal lung derived MSC were very similar compared to BM derived MSC, with only 235 and 338 genes, respectively, being significantly differently expressed. Out of the 235 genes that were significantly different between adult lung derived and BM derived MSC, 90 genes were higher expressed in the lung derived MSC. In case of fetal lung derived MSC, 166 genes were higher expressed compared to the BM derived MSC. Interestingly, only, 89 genes were found to be expressed differently when comparing BM derived MSC to both, fetal and adult lung derived MSC, indicating that these genes are lung specific. Next, we went on to evaluate if MSC isolated from biopsies of lung-transplanted patients with BOS differed compared to patients without BOS, i.e. good outcome recipients. Here we found that four genes (Sox9, FAR2, LOC728855 and NDUFS5) were significantly higher expressed in MSC isolated from BOS patients Conclusions: This data demonstrates that lung resident MSC possess lung specific properties that should be taken into considerations when using MSC for cell-based therapy in severe lung disorders like BOS. These results also show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype. Comparison of gene expression of MSC isolated from bone marrow, adult lung and fetal lung.

ORGANISM(S): Homo sapiens  

SUBMITTER: Leif Eriksson   Katarina Le Blanc  Annika Andersson Sjöland  Ingrid Skog  Leif Bjermer  Lennart Hansson  Gunilla Westergren-Thorsson  Sara Rolandsson Enes  Stefan Scheding  Hillevi Larsson 

PROVIDER: E-GEOD-74163 | ArrayExpress | 2016-08-01



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MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC.

Rolandsson Enes Sara S   Andersson Sjöland Annika A   Skog Ingrid I   Hansson Lennart L   Larsson Hillevi H   Le Blanc Katarina K   Eriksson Leif L   Bjermer Leif L   Scheding Stefan S   Westergren-Thorsson Gunilla G  

Scientific reports 20160706

Mesenchymal stromal cells (MSC) are multipotent cells with regenerative and immune-modulatory properties. Therefore, MSC have been proposed as a potential cell-therapy for bronchiolitis obliterans syndrome (BOS). On the other hand, there are publications demonstrating that MSC might be involved in the development of BOS. Despite limited knowledge regarding the functional role of tissue-resident lung-MSC, several clinical trials have been performed using MSC, particularly bone marrow (BM)-derived  ...[more]

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