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Bone Marrow‐Derived Mesenchymal Stem Cells‐Mediated Protection Against Organ Dysfunction in Disseminated Intravascular Coagulation Is Associated With Peripheral Immune Responses
Author(s) -
Wang Biao,
Wu Shuming,
Wang Tao,
Ma Zengshan,
Liu Kai
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25964
Subject(s) - bone marrow , medicine , disseminated intravascular coagulation , mesenchymal stem cell , stem cell , population , immunology , pathology , biology , genetics , environmental health
ABSTRACT Disseminated intravascular coagulation (DIC) is a fatal thrombohemorrhagic disorder. Bone marrow‐derived mesenchymal stem cells (BMSCs) are multipotent stem cells that have tremendous therapeutic effect. Our aim was to explore whether the immune mechanisms were associated with BMSCs‐afforded protection against DIC. We generated a rat model of DIC by lipopolysaccharide (LPS, 3 mg/kg) injection via the tail vein. In the treatment group, rats were pre‐treated with 1 × l0 3 , 1 × l0 4 , 1 × l0 5 , and 1 × l0 6 allogeneic BMSCs before LPS injection. Blood sample was withdrawn from the abdominal aorta at 0 (before), 4, and 8 h after LPS injection and used for biochemical analyses. After experiments, the mice were sacrificed and their organs were harvested and observed by H&E and PTAH staining. Continuous infusion of LPS into the rats gradually impaired the hemostatic parameters and damaged organ functions. However, pre‐treatment with BMSCs dose‐dependently improved the hemostatic parameters. Meanwhile, the treatment significantly suppressed the fibrin microthrombi formation and alleviated liver, heart, lung, and renal injuries. Flow cytometry analysis demonstrated that BMSCs pre‐treatment inhibited LPS‐induced upregulation of CD3 + CD8 + T cells and CD3 + /CD161a + NKT cells in the peripheral blood. BMSCs pre‐treatment reversed the upregualtion of the B‐cell population and the percentage of CD43 + /CD172a + monocytes in the DIC models. Finally, BMSCs pre‐treatment decreased the levels of tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) and increased the levels of interleukin‐10 (IL‐10) in LPS‐induced DIC models. Pre‐treatment with BMSCs can reduce coagulation and alleviate organ dysfunction via peripheral immune responses in LPS‐induced DIC rat model. J. Cell. Biochem. 118: 3184–3192, 2017. © 2017 Wiley Periodicals, Inc.