To explore whether mesenchymal stem cell-derived exosomes can reduce the peritonitis induced by high glucose-based peritoneal dialysate.

Twenty-four male C57BL/6 mice aged 6-8 weeks, weighing 20-25 g, were randomly divided into 4 groups: normal control group, normal saline group, 4.25% glucose-containing peritoneal dialysate group, and 4.25% glucose-containing peritoneal dialysate plus exosomes group. The normal control group was not given any treatment. The normal saline group was given intraperitoneal injection of 0.9% normal saline (0.1 ml/g twice a day). The 4.25% glucose-containing peritoneal dialysate group was given intraperitoneal injection of 4.25% glucose-containing peritoneal dialysate (0.1 ml/g twice a day). The 4.25% glucose-containing peritoneal dialysate plus exosomes group was given intraperitoneal injection of both 4.25% glucose-containing peritoneal dialysate (0.1 ml/g twice a day) and exosomes (200 μl/kg on the 28th and 35th days). After six weeks of the intraperitoneal injection, the peritoneal transport and ultrafiltration function of the mice were evaluated. The parietal peritoneum samples were taken for PAS staining to assess the degree of peritoneal thickening. Immunohistochemistry methods were applied to detect the levels of MPO, F4/80, and CD68 for the assessment of inflammatory cell infiltration. Real-time quantitative PCR was used to detect the expression of inflammatory factors as IL-6, IL-1β, and TNF-α. GSL-1 was detected by immunohistochemistry for evaluating the degree of angiogenesis of microvessels and capillaries.

The peritoneal thickness of the 4.25% glucose-containing peritoneal dialysate group was significantly higher than that of the normal control group and the normal saline group (P<0.01). Compared with the 4.25% glucose-containing peritoneal dialysate group, the 4.25% glucose-containing peritoneal dialysate plus exosomes group showed lower levels in peritoneal thickness, the number of peritoneal mesothelial neutrophils and macrophages, the degree of peritoneal mesothelial neovascularization, and the mRNA expression of peritoneal inflammatory factors (IL-6, IL-1β, TNF-α) (P<0.05). Compared with the normal control group, the normal saline group, and the 4.25% glucose-containing peritoneal dialysate plus exosomes group, the 4.25% glucose-containing peritoneal dialysate group′s peritoneal function manifested a faster balance of glucose and stronger clearance of urea nitrogen, and a lower ultrafiltration function (P<0.05).

Stem cell-derived exosomes could significantly reduce the level of peritonitis induced by high glucose-based peritoneal dialysate, and improve the peritoneal ultrafiltration function.