Bone marrow-derived progenitor cells in end-stage lung disease patients

Abstract

BackgroundChronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45+Collagen-1+ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.MethodsUsing an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.ResultsAn increase in CD45+Collagen-1+ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP+ cells in both the BM and PB. The proportion of CCSP+ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP+ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.ConclusionsDifferent bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP+ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.

Depletion of Bone Marrow CCSP-Expressing Cells Delays Airway Regeneration

“…31,33,34 Independently of our research, Londhe et al 32 confirmed that CCSP + cells are found in bone marrow from wild-type mice treated with saline or ganciclovir, and, more importantly, they found that CCtk mice harbor thymidine kinase/CCSP dual-positive cells in the bone marrow. In accordance with these publications we corroborated that it is possible to isolate CCSP + BMC from CCtk and FVBn mice by FACS-sorting.…”

“…The existence of a population of cells that express CCSP in the bone marrow of human and mouse has been demonstrated by our group and others. [31][32][33][34] Further characterization of the CCSP + BMC by flow cytometry, FACS-sorting, real time PCR and immunofluorescence staining has demonstrated that these cells also express mesenchymal markers CD73, CD90, and CD105 but not CD106, collagen type I or collagen type IV. On the other hand these cells also express CD45 and CD34 which suggest the CCSP + BMC are a unique population that coexpresses hematopoietic and mesenchymal markers.…”

Involvement of fibrocytes in asthma and clinical implications

“…Similar to some fibroblasts and to myofibroblasts [15][16][17][18][19][20][21], they produce collagenous and non-collagenous extracellular matrix (ECM) molecules and also contribute to collagen degradation through the Endo180-mediated endocytosis pathway [8]. After the discovery of their role in wound healing, these cells have been implicated in the pathogenesis of several fibrotic disorders [22][23][24][25] and in the progression of diverse chronic inflammatory diseases, where persistent inflammation is driven by Toll-like receptor danger signals [10] or dysregulated T cell activation and autoimmunity [22,23,[26][27][28] and is associated with angiogenesis and excessive deposition of ECM molecules at the tissue sites [22][23][24][25][26][27][28]. Many studies from diverse laboratories and clinical centres have demonstrated the potential contribution of fibrocytes to the pathogenesis of airway remodelling in asthma [9, [29][30][31][32][33][34] and their major role in the acute exacerbations caused by allergen exposure and viral infections [11,29,35].…”

Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease

“…Flow cytometry on ex vivo blood/PBMCs has been utilized previously to identify and enumerate fibrocytes , but there is little consensus on how this should be achieved. We have applied a more rigorous flow cytometric protocol to determine whether constitutive collagen type 1 + cells present in PBMCs, in particular CD45 + , CD34 + (classical) fibrocytes, are important to COPD immunopathology.…”