MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC (original) (raw)

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 MSC, for various lung diseases. We aimed to compare lung-MSC with the well-characterized BM-MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to patients without BOS. Our study show that lung-MSCs are smaller, possess a higher colony-forming capacity and have a different cytokine profile compared to BM-MSC. Utilizing gene expression profiling, 89 genes including lung-specific FOXF1 and HOXB5 were found to be significantly different between BM-MSC and lung-MSC. No significant differences in cytokine secretion or gene expression were found between MSC isolated from BOS patients compared recipients without BOS. These data demonstrate that lung-resident MSC possess lung-specific properties. Furthermore, these results show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype compared to MSC isolated from good outcome recipients. Mesenchymal stromal cells (MSC) have potent immune-regulatory and regenerative functions and they are therefore promising candidates for cell therapy approaches to treat a variety of different diseases including severe diseases of the lung, such as idiopathic pulmonary fibrosis (IPF) 1 , chronic obstructive pulmonary disease (COPD) 2 and acute respiratory distress syndrome (ARDS) 3. The only curative treatment of severe lung diseases like IPF and COPD at present is lung-transplantation. However, chronic rejection, which is manifested as bronchiolitis obliterans syndrome (BOS)/obliterative bronchiolitis, is a severe complication affecting the survival after a lung-transplantation. The hallmark of this complication is the fibrotic obliteration of the peripheral airways 4 , which is a fibro-proliferative disease for which inflammation has been shown to be an important driving factor. It has therefore been suggested that MSC might be a treatment option. Although MSC have been used in clinical trials for the treatment of severe lung diseases, not much is known about the primary resident lung-MSC. Open questions are for example if the lung-MSC are altered in diseases such as BOS and how lung-resident MSC differ from the bone marrow (BM)-derived MSC, the predominant MSC source in clinical trials? Therefore, the current study aimed to investigate the tissue specificity of MSC isolated from lung tissues (fetal and adult) and to compare them to the extensively studied BM-derived MSC. Furthermore, we aimed to investigate whether MSC isolated from lung-transplanted patients with BOS were different from MSC isolated from good outcome recipients. Our results demonstrate that although lung-derived