title: The effect of adipose stem cell therapy on pulmonary fibrosis induced by repetitive intratracheal bleomycin in mice.
abstract: Adipose stem cells (ASCs) are detectable in the parenchyma and large airways of lungs after systemic administration, and ameliorate inflammatory infiltration and cell death in animal models of emphysema. We evaluated whether ASC treatment could attenuate lung fibrosis induced by repetitive intratracheal bleomycin administration. Male 8-week-old C57BL/6J mice (control group, bleomycin-only group, and bleomycin-plus-ASC group) were used. Eight biweekly doses of bleomycin were injected intratracheally via an intubation procedure at a dose of 0.04 units in a total volume of 100 μL of sterile saline. During the latter 2 months of the 4-month bleomycin exposure, human ASCs (3 × 10(5) cells) were administered repeatedly via intraperitoneal injection at the same time as bleomycin. Lung tissues were evaluated for histology, collagen content, TUNEL staining, and TGF-β levels. Bronchoalveolar lavage (BAL) was performed for cell counting. Administrations of ASCs ameliorated the deleterious effects of repetitive intratracheal instillation of bleomycin, namely hyperplasia of Club cells (Clara cells) and cuboidal alveolar epithelial cells, infiltration of the perialveolar ducts by inflammatory cells, septal thickening, enlarged alveoli, and extensive fibrosis. Addition of ASC led to suppression of bleomycin-induced epithelial cell apoptosis and expression of TGF-β. These results suggest a useful therapeutic effect of ASCs on pulmonary fibrosis induced by repetitive bleomycin administration. Further studies will be required to evaluate the efficacy of ASC therapy for the treatment of idiopathic pulmonary fibrosis.
authors.affiliation: 1Department of Anatomy, Korea University College of Medicine , Inchonro, Seoul , Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.forename: Chang Sub
authors.initials: CS
authors.lastname: Uhm
authors.forename: Han-Kyeom
authors.initials: HK
authors.lastname: Kim
authors.forename: Kyung-Sook
authors.initials: KS
authors.lastname: Yang
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Park
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Kim
authors.forename: Tai June
authors.initials: TJ
authors.lastname: Yoo
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006909:Hydroxyproline; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D001761:Bleomycin; D006909:Hydroxyproline