title: Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury.
abstract: BACKGROUND
  Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALI and the mechanisms involved.
  
  
  METHODS
  MSCs were isolated from male rat bone marrow and the ALI model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo.
  
  
  RESULTS
  There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P < 0.05), and myeloperoxidase activity in the lung (P < 0.01), and of TNF-α and IL-1β in serum (P < 0.05) in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-α, IL-1β and macrophage inflammatory protein (MIP)-1α and significantly increased levels of IL-10 (P < 0.05) in the culture supernatants.
  
  
  CONCLUSIONS
  Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALI in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.
authors: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors: Zhi-xin
authors: ZX
authors: Liang
authors: Ji-ping
authors: JP
authors: Sun
authors: Ping
authors: P
authors: Wang
authors: Qing
authors: Q
authors: Tian
authors: Zhen
authors: Z
authors: Yang
authors: Liang-an
authors: LA
authors: Chen
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004731:Endotoxins; D009195:Peroxidase