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.
Lee
Shin-Hwa
SH
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.
Jang
An-Soo
AS
Kim
Young-Eun
YE
Cha
Ji-Yeon
JY
Kim
Tae-Hoon
TH
Jung
Seok
S
Park
Seong-Kyu
SK
Lee
You-Kyoung
YK
Won
Jong-Ho
JH
Kim
Yong-Hoon
YH
Park
Choon-Sik
CS
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