Effect of bone marrow mesenchymal stem cells on the polarization of macrophages.
Mol Med Rep
; 17(3): 4449-4459, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29363724
ABSTRACT
Inflammation is a defensive response in the living tissue of the vascular system that acts against damage factors and involves various types of immune cells, including macrophages, neutrophils, endothelial cells and other associated immune molecules. If the release of inflammatory mediators is excessive, systemic inflammatory response syndrome may develop. Sepsis is the most common complication of severe burns and is a systemic inflammatory response syndrome that is caused by infectious factors and is capable of leading to multiple organ dysfunction and potentially death. Research concerning the mechanism and treatment of sepsis is crucial. Macrophages are an important type of immune cell that remove invasive pathogens and are involved in innate and adaptive immune responses. It has been previously reported that bone marrow mesenchymal stem cells (BMSCs) affect macrophages by regulating immunity. The present study aimed to investigate the effect of BMSCs on macrophage polarization in vivo and in vitro, in addition to the potential therapeutic effect of these cells on experimental sepsis. BMSCs and peritoneal macrophages were isolated from SpragueDawley rats and cocultured overnight as a mixed culture or Transwell system, and subsequently stimulated with 100 ng/ml lipopolysaccharide (LPS). After 12 h, the medium was replaced with normal complete medium for various durations and supernatants were collected to extract proteins and cells for ELISA, western blot and flow cytometry analysis to investigate different aspects of macrophages. Sepsis was induced in SpragueDawley rats by injection of LPS (5 mg/kg), followed by tail vein injection of BMSCs or PBS 1 h later. After 6, 12, 24 and 48 h, lung tissues were harvested for pathological observation and peritoneal macrophages were collected for flow cytometry analysis to assess the expression of markers, including cluster of differentiation (CD)68 (used for gating), CD11c and CD206. The results demonstrated that, in the culture medium, LPS stimulation increased the expression of CD11c in macrophages, and the levels of tumor necrosis factorα and inducible nitric oxide synthase were also increased. By contrast, in macrophages treated with BMSCs directly, the expression of CD11c was reduced compared with the LPSstimulated macrophage alone group. However, the secretion of interleukin10, transforming growth factorß and arginase1 was increased in the direct coculture group, compared with the LPSstimulated macrophage alone group. BMSCs reduced the inflammation in lung tissues and inhibited macrophage expression of CD11c in the rat model of sepsis. The results of the present study demonstrated that BMSCs cocultured with macrophages directly inhibited macrophage differentiation into the M1 phenotype and reduced inflammation in macrophages stimulated by LPS. In vivo, BMSCs decreased the expression of CD11c in peritoneal macrophages and reduced the pathological inflammatory response in the lungs. The findings of the present study demonstrated that BMSCs may reduce the extent of the systemic inflammatory response, which may contribute to the development for a novel type of treatment for sepsis in the future.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Macrófagos Peritoneales
/
Células Madre Mesenquimatosas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2018
Tipo del documento:
Article