Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis.
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-1beta, IL-6, TNF-alpha, TGF-beta 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.


CONCLUSIONS
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.
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.
Shin-Hwa
SH
Lee
An-Soo
AS
Jang
Young-Eun
YE
Kim
Ji-Yeon
JY
Cha
Tae-Hoon
TH
Kim
Seok
S
Jung
Seong-Kyu
SK
Park
You-Kyoung
YK
Lee
Jong-Ho
JH
Won
Yong-Hoon
YH
Kim
Choon-Sik
CS
Park
D000818:Animals; D001761:Bleomycin; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D055370:Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009569:Nitric Oxide / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D001761:Bleomycin; D009569:Nitric Oxide