Open Access Highly Accessed Research article

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

Sarah E Gilpin1, Kalvin Lung1, Geoffrey T de Couto2, Marcelo Cypel1, Masaaki Sato1, Lianne G Singer1, Shaf Keshavjee1 and Thomas K Waddell1*

Author Affiliations

1 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

2 Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, Ontario, Canada

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BMC Pulmonary Medicine 2013, 13:48  doi:10.1186/1471-2466-13-48

Published: 3 August 2013

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.

Keywords:
Fibrocytes; Clara cell; Lung progenitor; Migration