BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model

作者：Wang, Biao^*; Wu, Shuming; Ma, Zengshan; Wang, Tao; Yang, Changyong

来源：Cell Death & Disease, 2018, 9(10): 1024.

DOI：10.1038/s41419-018-1060-5

• MESENCHYMAL STEM-CELLS
• DISSEMINATED INTRAVASCULAR COAGULATION
• MARROW STROMAL CELLS
• ATTENUATES ORGAN DYSFUNCTION
• SUPPRESS T-LYMPHOCYTE
• INDOLEAMINE 2,3-DIOXYGENASE
• REPERFUSION INJURY
• INTERFERON-GAMMA
• PROLIFERATION
• INHIBITION

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on disseminated intravascular coagulation (DIC) model rats and to further explore the underlying mechanism. A rat model of lipopolysaccharide (LPS)-induced DIC was successfully established, as indicated by impaired plasma hemostatic parameters and damaged organ functions in rats. Importantly, pre-treatment with rat allogeneic BMSCs before LPS injection significantly alleviated systemic intravascular coagulation, reduced plasma levels of organ dysfunction indicators and pro-inflammatory cytokines, suppressed fibrin microthrombi formation, ameliorated liver, heart, and renal injuries, and increased 24-hour survival rates in LPS-induced DIC rats. The protection of BMSCs against DIC was in a moderately dose-dependent manner. Further investigation revealed that BMSCs co-cultured with peripheral blood mononuclear cells (PBMCs) significantly inhibited the LPS-stimulated PBMCs proliferation and the release of proinflammatory cytokines from PBMCs. Of note, upregulation of immunosuppressive factors including indoleamine 2,3-dioxygenase and interleukin-10, which was induced by interferon-gamma, contributed to BMSCs-mediated inhibition of LPS-stimulated PBMCs proliferation. These effects do not depend on the direct cell-cell contact. In conclusion, BMSCs pretreatment ameliorates inflammation-related tissue destruction in LPS-induced DIC model rats. The protection of BMSCs may be attributed to their anti-inflammatory and immunomodulatory properties, which render BMSCs a promising source for stem cell-based therapeutic approaches in inflammation-related DIC.

• 出版日期2018-10-3
• 单位山东大学