Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury

• Published in: Chinese medical journal Vol. 124; no. 17; pp. 2715 - 2722
• Main Authors: Liang, Zhi-xin, Sun, Ji-ping, Wang, Ping, Tian, Qing, Yang, Zhen, Chen, Liang-an
• Format: Journal Article
• Language: English
• Published: China Department of Respiratory Medicine,Chinese People's Liberation Army General Hospital,Beijing 100853,China%Department of Respiratory Medicine,General Hospital of Jinan Military Region,Jinan,Shandong 250031,China 01.09.2011
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - metabolism; Acute Lung Injury - therapy; Animals; Bone Marrow Cells - cytology; Cells, Cultured; Coculture Techniques; Endotoxins - toxicity; Female; Lung - metabolism; Lung - pathology; Macrophages, Alveolar - cytology; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Peroxidase - metabolism; Random Allocation; Rats; Rats, Wistar; 内毒素; 急性肺损伤; 支气管肺泡灌洗液; 细胞保护; 诱导; 间质干细胞; 雄性大鼠; 骨髓干细胞; mesenchymal stem cell; lung injury; lipopolysaccharide; co-culture
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2011.17.027

Background Acute lung injury （ALl） 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 ALl and the mechanisms involved. Methods MSCs were isolated from male rat bone marrow and the ALl 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 ALl 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.