Pre-treatment with bone marrow-derived mesenchymal stem cells inhibits systemic intravascular coagulation and attenuates organ dysfunction in lipopolysaccharide-induced disseminated intravascular coagulation rat model.
BACKGROUND
Bacterial lipopolysaccharide (LPS) can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation (DIC) during infection. In recent years, it has been found that bone marrow-derived mesenchymal stem cells (BMSCs) can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines. Here, we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism.


METHODS
Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group. In the treatment groups, 0, 1'10(6), 2'10(6), 3'10(6), and 5'10(6) of BMSCs were injected intravenously for 3 days before LPS injection, while the control group was treated with pure cell culture medium injection. Then, the LPS (3 mg/kg) was injected via the tail vein in the treatment groups, while the control group received 0.9% NaCl. Blood was withdrawn before and 4 and 8 hours after LPS administration. The following parameters were monitored: platelets (PLT), fibrinogen (Fib), D-dimer (D-D), activated partial thromboplastin time (APTT), prothrombin time (PT), tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), interleukin-1b (IL-1b), creatinine (Cr), alanine aminotransferase (ALT), creatinine kinase-MB (CK-MB), and endothelin (ET).


RESULTS
Compared with the control group, a significant change of coagulation parameters were found in the experimental groups. The plasma level of the inflammatory mediator (TNF-a, IFN-g, IL-1b), organ indicator (Cr, ALT, and CK-MB), and ET in the experimental groups were much lower (P < 0.05) than that in the control group. Furthermore, some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups (from group 2 to group 5) showed a significant difference (P < 0.05), except the ALT and CK-MB levels (P > 0.05).


CONCLUSIONS
Pre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune cells and proinflammatory cytokines in LPS-induced DIC rat model.
Department of Cardiovascular Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Biao
B
Wang
Shu-Ming
SM
Wu
Tao
T
Wang
Kai
K
Liu
Gong
G
Zhang
Xi-Quan
XQ
Zhang
Jian-Hua
JH
Yu
Chuan-Zhen
CZ
Liu
Chang-Cun
CC
Fang
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology; D003404:Creatinine / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003404:Creatinine; D000410:Alanine Transaminase