Research

Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis

Shin-Hwa Lee^1* , An-Soo Jang^1* , Young-Eun Kim¹ , Ji-Yeon Cha¹ , Tae-Hoon Kim¹ , Seok Jung¹ , Seong-Kyu Park² , You-Kyoung Lee³ , Jong-Ho Won⁴ , Yong-Hoon Kim⁵ and Choon-Sik Park¹

¹  Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-767, Korea

²  Division of Hematology, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-767, Korea

³  Clinical Laboratory Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-767, Korea

⁴  Division of Hematology, Soonchunhyang University Seoul Hospital, 657-58, Hannam-dong, Yongsan-gu, Seoul, 140-743, Korea

⁵  Division of Allergy and Respiratory Diseases, Soonchunhyang University Hospital, 23-20, Bongmyung-dong, Cheonan city, Choongnam, 330-721, Korea

author email corresponding author email* Contributed equally

Respiratory Research 2010, 11:16doi:10.1186/1465-9921-11-16

Published:	8 February 2010

Abstract

Background

No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production.

Methods

BMDMSCs were transferred 4 days after BLM inhalation. Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and deposition of collagen were analyzed.

Results

Nitrite, nitrate and cytokines were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic inflammation, and amount of collagen were elevated in BLM-treated rats compared to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1β, IL-6, TNF-α, TGF-β and VEGF were also higher at day 7 (p < 0.05). Degree of lymphocyte and macrophage infiltration increased steadily over time. BMDMSC transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree of neutrophilic infiltration, collagen deposition, and levels of the cytokines, nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in situ hybridization localized the engrafted cells to areas of lung injury.

Conclusion

Systemic transfer of BMDMSCs effectively reduced the BLM-induced lung injury and fibrosis through the down-regulation of nitric oxide metabolites, and proinflammatory and angiogenic cytokines.