Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Wu,Yuanfan; Zhou,Jing; Bi,Liqing; Huang,Min; Han,Yi; Zhang,Qian; Zhu,Dongmei; Zhou,Suming

doi:10.3892/mmr.2016.5151

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Authors:
- Yuanfan Wu
- Jing Zhou
- Liqing Bi
- Min Huang
- Yi Han
- Qian Zhang
- Dongmei Zhu
- Suming Zhou
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Affiliations: Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: April 20, 2016 https://doi.org/10.3892/mmr.2016.5151
Pages: 5317-5325

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Abstract

The present study aimed to investigate the effects of bone marrow mesenchymal stem cells (MSCs) on the cardiac function and immune system of mice with endotoxemia. The mice were divided into the following groups: Control group, endotoxemia group, lipopolysaccharide (LPS) treatment group, LPS and MSC treatment group (LPS + MSC group) and MSC group. Following treatment with LPS, the cardiac function of the mice was examined at after 2, 6 and 24 h, and on day 7. An enzyme‑linked immunofluorescent assay was used to analyze the serum and the levels of cytokines in the myocardium, and western blotting was used to investigate any changes in the levels of signaling proteins associated with the myocardium. A 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2H‑tetrazolium bromide assay was used to investigate the growth rate of the splenic cells at after 24 h and on day 7, and the humoral immune function and phagocytosis of the macrophages in the mice were also examined. The cardiac function of the mice with endotoxemia declined, although this impairment was circumvented following treatment with MSCs. The levels of interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α and IL‑10 in the serum and the myocardium increased following stimulation by LPS, although these declined as a result of MSC treatment. The expression levels of Toll‑like receptor 4, p65‑nuclear factor‑κB and phosphorylated p38 in the mouse myocardium were enhanced following stimulation by LPS, which subsequently decreased as a result of MSC treatment. Compared with the control group, the growth rate of the splenic cells, humoral immune function and the level of phagocytosis of macrophages were all increased, although these parameters declined following treatment with MSCs. Taken together, the present study revealed that the MSCs inhibited the inflammatory reaction in the mice with endotoxemia, and improved cardiac function. By contrast, the cellular and humoral immunity were depressed, and phagocytosis of the macrophages, which were enhanced following simulation with LPS, were decreased following treatment with MSCs. However, no overexpression of the anti‑inflammatory factor, IL‑10, was observed. The present study hypothesized that MSCs exert a bifunctional role in endotoxemia, by inhibiting inflammatory factors, including IL‑1 and IL‑6, and inhibiting the compensatory expression of IL‑10 following LPS stimulation. This avoids the possibility of excessive inhibition of immunological function, as this results in immunosuppression, and a higher ratio of IL‑10 to TNF‑α is indicative of a poor prognosis in patients with sepsis.

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