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

Abstract

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.

Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture

“…4f). These data are not consistent with literature reports published previously in which MSC treatment was found to decrease the levels of IL-1β in LPS-activated or other inflammasome-activated Mφs [51, 52]. However, RAW264.7 cells were not exposed to proinflammatory stimuli prior to coculture with BMSCs.…”

Immunomodulatory and Therapeutic Effects of Mesenchymal Stem Cells on Organ Dysfunction in Sepsis

“…Wu et al (73) revealed that the administration of MSCs to mice sepsis model caused by LPS could restore the function of the cardiovascular system. The results indicated that MSCs lead to a decrease in the inflammatory responses of the myocardium by downregulating the TLR4 and nuclear factor (NF)-kB, as well as by declining the levels of pro-inflammatory cytokines (such as IL-1b, IL-6, and TNF-a) in serum and myocardium (73).…”

“…Wu et al (73) revealed that the administration of MSCs to mice sepsis model caused by LPS could restore the function of the cardiovascular system. The results indicated that MSCs lead to a decrease in the inflammatory responses of the myocardium by downregulating the TLR4 and nuclear factor (NF)-kB, as well as by declining the levels of pro-inflammatory cytokines (such as IL-1b, IL-6, and TNF-a) in serum and myocardium (73). Following the injection of LPS, the levels of the ejection fraction (EF) were declined significantly, but the administration of MSCs probably recovered the EF by regulating the secretion of the pro-inflammatory cytokines (73).…”

Advances and Prospects in Stem Cells for Cartilage Regeneration

“…Today, such treatment is an important branch of regenerative medicine. Stem cells have two effects: they have the potential for multiple differentiation and they have paracrine and immunomodulatory abilities, which are both important features in cartilage regeneration using MSCs [ 117 , 118 ]. The fact that stem cells can differentiate into cartilage cells and that a scaffold can be utilized for cell attachment makes this system amenable to cartilage tissue engineering with stem cells in the clinic.…”