Bone Marrow-derived Mesenchymal Stem Cells-mediated Protection Against Organ Dysfunction in Disseminated Intravascular Coagulation Is Associated with Peripheral Immune Responses.

Wang B, Wu S, Wang T et al.

Department of Cardiovascular Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China.

Journal of cellular biochemistry. Mar 2017.

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 Blood sample was withdrawn from the abdominal aorta at 0 h (before), 4 h and 8 h after LPS injection and used for biochemical analyses.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. This article is protected by copyright. All rights reserved.


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