Identification of a bone marrow-derived epithelial-like population capable of repopulating injured mouse airway epithelium.
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.
Wong
Amy P
AP
Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, and the McEwen Centre in Regenerative Medicine, Toronto, Ontario, Canada.
Keating
Armand
A
Lu
Wei-Yang
WY
Duchesneau
Pascal
P
Wang
Xinghua
X
Sacher
Adrian
A
Hu
Jim
J
Waddell
Thomas K
TK
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D000071063:Endoglin; D004847:Epithelial Cells / Q000502:physiology* / Q000637:transplantation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D055370:Lung Injury / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000032:analysis; D012038:Regeneration
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017493:Leukocyte Common Antigens