title: Bone Marrow-Derived Mesenchymal Stem Cells-Mediated Protection Against Organ Dysfunction in Disseminated Intravascular Coagulation Is Associated With Peripheral Immune Responses.
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 × l03, 1 × l04, 1 × l05, and 1 × l06allogeneic 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 Blood sample was withdrawn from the abdominal aorta at 0 (before), 4, and 8 h after LPS injection and used for biochemical analyses.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.
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong, University, Jinan, Shandong, 250012, China.
authors.forename: Biao
authors.identifier: 0000-0003-2633-5688
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong, University, Jinan, Shandong, 250012, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong, University, Jinan, Shandong, 250012, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong, University, Jinan, Shandong, 250012, China.
authors.forename: Zengshan
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong, University, Jinan, Shandong, 250012, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
mesh_terms: D064591:Allografts; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides
keywords: BONE MESENCHYMAL STEM CELLS; CYTOKINE; DISSEMINATED INTRAVASCULAR COAGULATION; IMMUNE CELLS; LIPOPOLYSACCHARIDE