The effect of adipose stem cell therapy on pulmonary fibrosis induced by repetitive intratracheal bleomycin in mice

Sang Hoon Lee, Eun Joo Lee, Sang Yeub Lee, Je Hyeong Kim, Jae Jeong Shim, Chol Shin, Kwang Ho In, Kyung Ho Kang, Chang Sub Uhm, Han Kyeom Kim, Kyung Sook Yang, Sanghoon Park, Hyun Soo Kim, Yong Man Kim, Tai June Yoo

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27 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)117-125
Number of pages9
JournalExperimental Lung Research
Volume40
Issue number3
DOIs
Publication statusPublished - 2014 Apr

Keywords

  • Adipose stem cell
  • Bleomycin
  • Cell therapy
  • Mouse
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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  • Cite this

    Lee, S. H., Lee, E. J., Lee, S. Y., Kim, J. H., Shim, J. J., Shin, C., In, K. H., Kang, K. H., Uhm, C. S., Kim, H. K., Yang, K. S., Park, S., Kim, H. S., Kim, Y. M., & Yoo, T. J. (2014). The effect of adipose stem cell therapy on pulmonary fibrosis induced by repetitive intratracheal bleomycin in mice. Experimental Lung Research, 40(3), 117-125. https://doi.org/10.3109/01902148.2014.881930