Sodium Alginate Microgel-Wrapped Primary Human Peritoneal Mesothelial Cells for the Treatment of Peritoneal Fibrosis Caused by Dialysis via the POSTN/NF-κB/CXCL8 Pathway

Background: Peritoneal fibrosis is a significant complication arising from long-term peritoneal dialysis (PD), primarily due to the loss of peritoneal mesothelial cells (PMCs). Recent studies have implicated periostin (POSTN) in the progression of various fibrotic diseases; however, its specific role in PD-induced peritoneal fibrosis remains unclear. Sodium alginate (SA) microgels have emerged as promising carriers for cell encapsulation in tissue engineering and regenerative medicine. This study investigated the therapeutic potential of PMCs encapsulated in SA microgels (SA/PMC) for reducing PD-induced peritoneal fibrosis, with a focus on the modulation by the periostin/nuclear factor kappa-B (NF-κB)/CXCL8 signaling pathway. Methods: Primary human peritoneal mesothelial cells (PHPMCs) were isolated from the PD effluent of patients. The effect of SA encapsulation on PMCs proliferation was evaluated using a Cell Counting Kit 8 (CCK-8) assay. The expression levels of POSTN, NF-κB p65, and CXCL8, as well as fibrosis markers, including α-smooth muscle actin (α-SMA), collagen I, transforming growth factor-β (TGF-β), and fibronectin, were evaluated in patients undergoing PD and a PD mouse model. Results: Patients undergoing PD for 1 year exhibited elevated levels of POSTN, NF-κB p65, CXCL8, and fibrosis markers compared with those undergoing PD for 1 week. Conclusions: Consistent results from in vivo and in vitro models demonstrated that PD and hyperglycemic conditions upregulated the expression of POSTN, NF-κB p65, CXCL8, and profibrotic markers, leading to peritoneal thickening and fibrotic progression. Treatment with SA/PMC microgels ameliorated these effects. By modulating the POSTN/NF-κB/CXCL8 pathway and enhancing PMCs survival, SA/PMC microgels may have therapeutic potential in mitigating peritoneal fibrosis in PD patients.