Limits...
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.

Show MeSH

Related in: MedlinePlus

Differential progenitor cell profiles in end-stage lung disease patients. (A) Percentage of bone marrow cells (BMCs) positive for CCSP in each disease group (n = 26 donor, n = 5 Bronchiolitis Obliterans (BO), n = 27 Cystic Fibrosis (CF), n = 34 Chronic Obstructive Pulmonary Disease (COPD), n = 41 Pulmonary Fibrosis (PF), n = 11 Pulmonary Hypertension (PH)). (B) Percentage of peripheral blood mononuclear cells (PBMCs) positive for CCSP in each disease group. (n = 29 donor, n = 6 BO, n = 33 CF, n = 41 COPD, n = 53 PF, n = 13 PH). (C) Percentage of peripheral blood leukocytes (PBLs) positive for CD45 and collagen-1 in each disease group (n = 17 donor, n = 6 BO, n = 14 CF, n = 22 COPD, n = 26 PF, n = 8 PH). (D) Ratio of CCSP+ PBMCs to CD45+collagen-1+ fibrocytes in each disease group, compared to lung donors (n = 13 donor, n = 6 BO, n = 10 CF, n = 17 COPD, n = 18 PF, n = 8 PH). Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750607&req=5

Figure 2: Differential progenitor cell profiles in end-stage lung disease patients. (A) Percentage of bone marrow cells (BMCs) positive for CCSP in each disease group (n = 26 donor, n = 5 Bronchiolitis Obliterans (BO), n = 27 Cystic Fibrosis (CF), n = 34 Chronic Obstructive Pulmonary Disease (COPD), n = 41 Pulmonary Fibrosis (PF), n = 11 Pulmonary Hypertension (PH)). (B) Percentage of peripheral blood mononuclear cells (PBMCs) positive for CCSP in each disease group. (n = 29 donor, n = 6 BO, n = 33 CF, n = 41 COPD, n = 53 PF, n = 13 PH). (C) Percentage of peripheral blood leukocytes (PBLs) positive for CD45 and collagen-1 in each disease group (n = 17 donor, n = 6 BO, n = 14 CF, n = 22 COPD, n = 26 PF, n = 8 PH). (D) Ratio of CCSP+ PBMCs to CD45+collagen-1+ fibrocytes in each disease group, compared to lung donors (n = 13 donor, n = 6 BO, n = 10 CF, n = 17 COPD, n = 18 PF, n = 8 PH). Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.

Mentions: No significant relationships were identified when these progenitor cell populations were analysed by age, gender, or BMI (data not shown). There were significant differences in the proportion of bone marrow-derived cells populations based on underlying lung disease. An increase in the proportion of CCSP+ cells was found in the bone marrow of CF patients when compared to lung donors (CF median = 1.33%, Donor median = 0.98, p < 0.05) (Figure 2A). We chose to use lung transplant donors as a comparison group as we had access to sternal marrow biopsy material obtained using identical collection techniques, not easily obtained in any other way. Different cell proportions were also found for CCSP+ cells in the peripheral blood. Specifically, CF patients had a greater proportion of CCSP+ cells when compared to lung donors (2.28% CF vs. 1.90% Donor, p < 0.05) (Figure 1B), while BO patients had a significantly lower proportion of CCSP+ PBMCs compared to donors (0.55% vs. 1.90% Donor, p < 0.05). When circulating CD45+collagen-1+ fibrocytes were compared between disease groups, an increased proportion was found in both BO patients (p < 0.001) and PF (p < 0.05) patients, when compared to Donors (Median BO = 7.02%, Median PF = 2.07%, Median Donors = 0.85%) (Figure 2C). As the changes in cell numbers appeared to reciprocal, the ratio of fibrocytes-to-CCSP+ PBMCs was calculated, and a similar pattern was found, where a predominantly fibrotic phenotype is represented in BO and PF, but not in other lung pathologies (Figure 2D).


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)

Differential progenitor cell profiles in end-stage lung disease patients. (A) Percentage of bone marrow cells (BMCs) positive for CCSP in each disease group (n = 26 donor, n = 5 Bronchiolitis Obliterans (BO), n = 27 Cystic Fibrosis (CF), n = 34 Chronic Obstructive Pulmonary Disease (COPD), n = 41 Pulmonary Fibrosis (PF), n = 11 Pulmonary Hypertension (PH)). (B) Percentage of peripheral blood mononuclear cells (PBMCs) positive for CCSP in each disease group. (n = 29 donor, n = 6 BO, n = 33 CF, n = 41 COPD, n = 53 PF, n = 13 PH). (C) Percentage of peripheral blood leukocytes (PBLs) positive for CD45 and collagen-1 in each disease group (n = 17 donor, n = 6 BO, n = 14 CF, n = 22 COPD, n = 26 PF, n = 8 PH). (D) Ratio of CCSP+ PBMCs to CD45+collagen-1+ fibrocytes in each disease group, compared to lung donors (n = 13 donor, n = 6 BO, n = 10 CF, n = 17 COPD, n = 18 PF, n = 8 PH). Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Differential progenitor cell profiles in end-stage lung disease patients. (A) Percentage of bone marrow cells (BMCs) positive for CCSP in each disease group (n = 26 donor, n = 5 Bronchiolitis Obliterans (BO), n = 27 Cystic Fibrosis (CF), n = 34 Chronic Obstructive Pulmonary Disease (COPD), n = 41 Pulmonary Fibrosis (PF), n = 11 Pulmonary Hypertension (PH)). (B) Percentage of peripheral blood mononuclear cells (PBMCs) positive for CCSP in each disease group. (n = 29 donor, n = 6 BO, n = 33 CF, n = 41 COPD, n = 53 PF, n = 13 PH). (C) Percentage of peripheral blood leukocytes (PBLs) positive for CD45 and collagen-1 in each disease group (n = 17 donor, n = 6 BO, n = 14 CF, n = 22 COPD, n = 26 PF, n = 8 PH). (D) Ratio of CCSP+ PBMCs to CD45+collagen-1+ fibrocytes in each disease group, compared to lung donors (n = 13 donor, n = 6 BO, n = 10 CF, n = 17 COPD, n = 18 PF, n = 8 PH). Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.
Mentions: No significant relationships were identified when these progenitor cell populations were analysed by age, gender, or BMI (data not shown). There were significant differences in the proportion of bone marrow-derived cells populations based on underlying lung disease. An increase in the proportion of CCSP+ cells was found in the bone marrow of CF patients when compared to lung donors (CF median = 1.33%, Donor median = 0.98, p < 0.05) (Figure 2A). We chose to use lung transplant donors as a comparison group as we had access to sternal marrow biopsy material obtained using identical collection techniques, not easily obtained in any other way. Different cell proportions were also found for CCSP+ cells in the peripheral blood. Specifically, CF patients had a greater proportion of CCSP+ cells when compared to lung donors (2.28% CF vs. 1.90% Donor, p < 0.05) (Figure 1B), while BO patients had a significantly lower proportion of CCSP+ PBMCs compared to donors (0.55% vs. 1.90% Donor, p < 0.05). When circulating CD45+collagen-1+ fibrocytes were compared between disease groups, an increased proportion was found in both BO patients (p < 0.001) and PF (p < 0.05) patients, when compared to Donors (Median BO = 7.02%, Median PF = 2.07%, Median Donors = 0.85%) (Figure 2C). As the changes in cell numbers appeared to reciprocal, the ratio of fibrocytes-to-CCSP+ PBMCs was calculated, and a similar pattern was found, where a predominantly fibrotic phenotype is represented in BO and PF, but not in other lung pathologies (Figure 2D).

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