title: Bone marrow cells expressing clara cell secretory protein increase epithelial repair after ablation of pulmonary clara cells.
abstract: We have previously reported a subpopulation of bone marrow cells (BMC) that express Clara cell secretory protein (CCSP), generally felt to be specific to lung Clara cells. Ablation of lung Clara cells has been reported using a transgenic mouse that expresses thymidine kinase under control of the CCSP promoter. Treatment with ganciclovir results in permanent elimination of CCSP(+) cells, failure of airway regeneration, and death. To determine if transtracheal delivery of wild-type bone marrow CCSP(+) cells is beneficial after ablation of lung CCSP(+) cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP(+) or CCSP(-) BMC. Compared with mice administered CCSP(-) cells, mice treated with CCSP(+) cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. Although donor CCSP(+) cells did not substantially repopulate the airway, their administration resulted in increased host ciliated cells, better preservation of airway epithelium, reduction of inflammatory cells, and an increase in animal survival time. Administration of CCSP(+) BMC is beneficial after permanent ablation of lung Clara cells by increasing bronchial epithelial repair. Therefore, CCSP(+) BMC could be important for treatment of lung diseases where airways re-epithelialization is compromised.
authors.affiliation: Division of Thoracic Surgery, Latner Thoracic Surgery Research Laboratories and McEwen Centre for Regenerative Medicine, University of Toronto, Toronto General Hospital, Toronto Medical Discovery Tower, Toronto, Ontario, Canada.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bustos
authors.forename: Marco
authors.initials: M
authors.lastname: Mura
authors.forename: Paula
authors.initials: P
authors.lastname: Marcus
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.forename: Olga
authors.initials: O
authors.lastname: Ludkovski
authors.forename: Amy P
authors.initials: AP
authors.lastname: Wong
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D055745:Bronchioles / Q000166:cytology* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008171:Lung Diseases / Q000628:therapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D062326:Re-Epithelialization; D012137:Respiratory System / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism
chemical_list: D014598:Uteroglobin; D013937:Thymidine Kinase