Anti-inflammatory roles of mesenchymal stem cells during acute Streptococcus pneumoniae pulmonary infection in mice

• Project/Area Number: 15K19591
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Keio University
• Principal Investigator: TAKAHIRO ASAMI 慶應義塾大学, 医学部(信濃町), 助教 (50623865)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 間葉系幹細胞 / 肺炎球菌肺炎 / 肺炎球菌

Outline of Final Research Achievements

The purpose of the study was to investigate whether MSCs have an anti-inflammatory protective role in pneumococcal pneumonia. After stimulation with TLR2, TLR9, or TLR4 ligands, TNF-alpha and IL-6 levels were significantly decreased, whereas IL-10 was significantly increased in bone marrow-derived macrophages (BMDMs) cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection. Levels of proinflammatory cytokines including TNF-alpha, IL-6, GM-CSF, and IFN-gammma were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumonia.