Identification of a bone marrow–derived epithelial-like population capable of repopulating injured mouse airway epithelium
Amy P. Wong, … , Jim Hu, Thomas K. Waddell
Amy P. Wong, … , Jim Hu, Thomas K. Waddell
Published January 26, 2009
Citation Information: J Clin Invest. 2009;119(2):336-348. https://doi.org/10.1172/JCI36882.
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Research Article Pulmonology

Identification of a bone marrow–derived epithelial-like population capable of repopulating injured mouse airway epithelium

Abstract

The bone marrow compartment is enriched in stem and progenitor cells, and an unidentified subpopulation of these cells can contribute to lung epithelial repair. Here we identify this subpopulation and quantitate its relative contribution to injured airway epithelium. A subpopulation of adherent human and murine bone marrow cells that expresses Clara cell secretory protein (CCSP) was identified using flow cytometry. When cultured at the air-liquid interface in ex vivo cultures, Ccsp+ cells expressed type I and type II alveolar markers as well as basal cell markers and active epithelial sodium channels. Ccsp+ cells preferentially homed to naphthalene-damaged airways when delivered transtracheally or intravenously, with the former being more efficient than the latter. Interestingly, naphthalene-induced lung damage transiently increased Ccsp expression in bone marrow and peripheral circulation. Furthermore, lethally irradiated Ccsp-null mice that received tagged wild-type bone marrow contained donor-derived epithelium in both normal and naphthalene-damaged airways. This study therefore identifies what we believe to be a newly discovered cell in the bone marrow that might have airway reconstitution potential in the context of cell-based therapies for lung disease. Additionally, these data could reconcile previous controversies regarding the contribution of bone marrow to lung regeneration.

Authors

Amy P. Wong, Armand Keating, Wei-Yang Lu, Pascal Duchesneau, Xinghua Wang, Adrian Sacher, Jim Hu, Thomas K. Waddell

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Figure 6

Endogenous bone marrow Ccsp+ cells can repopulate the airway epithelium.

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Endogenous bone marrow Ccsp+ cells can repopulate the airway epithelium....
(A–K) Representative double immunofluorescence staining for GFP (green) and Ccsp (red) of lung sections from bone marrow transplant recipient mice that received Ccsp+Sca-1+ cells from GFP+ donors. Asterisks indicate a GFP+ cell that was Ccsp–. White arrows point to donor-derived Ccsp+ cells. Red arrows point to Ccsp+ cells that were not donor derived. (A) GFP+ (positive control) lung. (B) Isotype staining of lung from bone marrow transplant recipient. (C–E) Bone marrow transplant recipients had a wild-type background. (C) Low-power image. (D and E) High-power images. (F–H) Bone marrow transplant recipients were Ccsp–/–. Sixty days following bone marrow transplant without naphthalene. (F) Low-power image. (G and H) High-power image. (I and K) Thirty days after bone marrow transplant with naphthalene injury. (I) Low-power image. (J and K) High-power image. Scale bars: 20 μm. Original magnification, ×60 (A, B, C, F, and I); ×90 (D, H, and J); ×120 (E, G, K). (L) Quantification of donor Ccsp+ cells in the airways. Each bar represents mean ± SEM (n = 3 per group). *P < 0.01 compared with uninjured WT group; †P < 0.05 compared with uninjured WT group; ‡P < 0.001 compared with injured WT group.