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

Gilpin SE, Lung K, de Couto GT, Cypel M, Sato M, Singer LG, Keshavjee S, Waddell TK - BMC Pulm Med (2013)

Bottom Line: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients.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.An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found.

View Article: PubMed Central - HTML - PubMed

Affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.

ABSTRACT

Background: Chronic 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.

Methods: Using 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.

Results: An 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.

Conclusions: Different 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.

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Plasma protein concentration and progenitor cell numbers. (A) The relationship between plasma Stem Cell Growth Factor (SCGF)-β levels and the percentage of CCSP+ bone marrow cells (BMCs) (n = 44) or CCSP+ peripheral blood mononuclear cells (PBMCs) in lung transplant recipients (R) and donors (D), and healthy controls (BMC: n = 35R, 9D. PBMC: (n = 49R, 9D, 8H). (B) The relationship between plasma Monocyte Chemotactic Protein (MCP)-1 levels and the percentage of CD45+Collagen-1+ fibrocytes in lung transplant recipients and donors, and healthy controls (n = 29R, 6D, 2H). Spearman rank test with correlation coefficient.
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Figure 8: Plasma protein concentration and progenitor cell numbers. (A) The relationship between plasma Stem Cell Growth Factor (SCGF)-β levels and the percentage of CCSP+ bone marrow cells (BMCs) (n = 44) or CCSP+ peripheral blood mononuclear cells (PBMCs) in lung transplant recipients (R) and donors (D), and healthy controls (BMC: n = 35R, 9D. PBMC: (n = 49R, 9D, 8H). (B) The relationship between plasma Monocyte Chemotactic Protein (MCP)-1 levels and the percentage of CD45+Collagen-1+ fibrocytes in lung transplant recipients and donors, and healthy controls (n = 29R, 6D, 2H). Spearman rank test with correlation coefficient.

Mentions: To further investigate the function of plasma protein mediators in progenitor cell recruitment, the relationship between protein concentration and cell numbers was analyzed. The number of CCSP+ cells in the bone marrow and peripheral blood significantly correlated with the plasma concentration of Stem Cell Growth Factor-beta SCGF-β (Figure 8A) in a range of samples, including lung transplant recipients, donors, and control samples. In addition, it was further found that fibrocyte numbers correlated with the plasma concentration of MCP-1 (Figure 8B).


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

Gilpin SE, Lung K, de Couto GT, Cypel M, Sato M, Singer LG, Keshavjee S, Waddell TK - BMC Pulm Med (2013)

Plasma protein concentration and progenitor cell numbers. (A) The relationship between plasma Stem Cell Growth Factor (SCGF)-β levels and the percentage of CCSP+ bone marrow cells (BMCs) (n = 44) or CCSP+ peripheral blood mononuclear cells (PBMCs) in lung transplant recipients (R) and donors (D), and healthy controls (BMC: n = 35R, 9D. PBMC: (n = 49R, 9D, 8H). (B) The relationship between plasma Monocyte Chemotactic Protein (MCP)-1 levels and the percentage of CD45+Collagen-1+ fibrocytes in lung transplant recipients and donors, and healthy controls (n = 29R, 6D, 2H). Spearman rank test with correlation coefficient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750607&req=5

Figure 8: Plasma protein concentration and progenitor cell numbers. (A) The relationship between plasma Stem Cell Growth Factor (SCGF)-β levels and the percentage of CCSP+ bone marrow cells (BMCs) (n = 44) or CCSP+ peripheral blood mononuclear cells (PBMCs) in lung transplant recipients (R) and donors (D), and healthy controls (BMC: n = 35R, 9D. PBMC: (n = 49R, 9D, 8H). (B) The relationship between plasma Monocyte Chemotactic Protein (MCP)-1 levels and the percentage of CD45+Collagen-1+ fibrocytes in lung transplant recipients and donors, and healthy controls (n = 29R, 6D, 2H). Spearman rank test with correlation coefficient.
Mentions: To further investigate the function of plasma protein mediators in progenitor cell recruitment, the relationship between protein concentration and cell numbers was analyzed. The number of CCSP+ cells in the bone marrow and peripheral blood significantly correlated with the plasma concentration of Stem Cell Growth Factor-beta SCGF-β (Figure 8A) in a range of samples, including lung transplant recipients, donors, and control samples. In addition, it was further found that fibrocyte numbers correlated with the plasma concentration of MCP-1 (Figure 8B).

Bottom Line: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients.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.An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found.

View Article: PubMed Central - HTML - PubMed

Affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.

ABSTRACT

Background: Chronic 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.

Methods: Using 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.

Results: An 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.

Conclusions: Different 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.

Show MeSH
Related in: MedlinePlus