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Adipose stem cell therapy in mice on repetitive intratracheal bleomycin induced pulmonary fibrosis

Sang Hoon Lee, Eun Joo Lee, Seung Hyeun Lee, Gyu Young Hur, Sung Yong 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
European Respiratory Journal 2012 40: P1773; DOI:
Sang Hoon Lee
1Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea
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Eun Joo Lee
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Seung Hyeun Lee
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Gyu Young Hur
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Sung Yong Lee
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Sang Yeub Lee
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Je Hyeong Kim
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Jae Jeong Shim
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Chol Shin
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Kwang Ho In
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Kyung Ho Kang
2Division of Respiratory and Critical Care Medicine, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Chang Sub Uhm
1Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea
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Han-Kyeom Kim
3Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Kyung-Sook Yang
4Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
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Sanghoon Park
5Department of Internal Medicine, KEPCO Medical Foundation Hanil General Hospital, Seoul, Republic of Korea
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Hyun Soo Kim
6Department of Internal Medicine, Pharmicell Co.,Ltd, Seongnam-si, Republic of Korea
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Yong Man Kim
6Department of Internal Medicine, Pharmicell Co.,Ltd, Seongnam-si, Republic of Korea
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Abstract

Rationale: Adipose-derived stem cells are detectable in the parenchyma and large airways of lungs, and associated with reduced inflammatory infiltration and lung cell death.

Objectives: We hypothesized that adipose stem cells would ameliorate lung fibrosis induced repetitive intratracheal bleomycin instillation.

Methods: Male 8-week-old C57BL/6J mice (control group n=10, bleomycin only group n=20, bleomycin plus adipose stem cell group n=10) were used. Eighth biweekly dose of bleomycin was injected intratracheally via an intubation procedure at dose of 0.04 units in a total volume of 100 μl of sterile saline. Human ASC (6×105 cells) were administered systemically via intraperitoneal injection every other week during the last 2 months of the 4- month bleomycin exposure. Lungs were evaluated for fibrosis and collagen content. Bronchoalveolar lavage (BAL) was performed for cell counts.

Measurements and Main Results: Evaluation of lung histology from mice receiving repetitive dosing revealed patchy distributive lung fibrosis and extracellular matrix deposition based on trichrome blue collagen staining. Furthermore, alveolar ducts were increased in size and proliferated with several Clara cells and cuboidal epithelial cells hyperplasia with peri-alveolar ducts inflammatory infiltrations. These finding was ameliorated by adipose stem cells administration.

Conclusions: These results suggest a useful therapeutic effect of adipose stem cells on pulmonary fibrosis induced by repetitive bleomycin administration. Further studies are needed to evaluate the efficacy of adipose stem cells for the treatment of human IPF.

  • Idiopathic pulmonary fibrosis
  • Animal models
  • Interstitial lung disease
  • © 2012 ERS
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Adipose stem cell therapy in mice on repetitive intratracheal bleomycin induced pulmonary fibrosis
Sang Hoon Lee, Eun Joo Lee, Seung Hyeun Lee, Gyu Young Hur, Sung Yong 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
European Respiratory Journal Sep 2012, 40 (Suppl 56) P1773;

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Adipose stem cell therapy in mice on repetitive intratracheal bleomycin induced pulmonary fibrosis
Sang Hoon Lee, Eun Joo Lee, Seung Hyeun Lee, Gyu Young Hur, Sung Yong 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
European Respiratory Journal Sep 2012, 40 (Suppl 56) P1773;
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