Paracrine effects of transplanted mesothelial cells isolated from temperature-sensitive SV40 large T-antigen gene transgenic rats during peritoneal repair

BACKGROUND: The prevention and restoration of peritoneal damage is a critical mission in peritoneal dialysis (PD). Transplantation of mesothelial cells has been suggested to suppress peritoneal injury during PD. Few studies have examined the efficacy and safety of cell transplantation. We evaluated the paracrine effects of mesothelial transplantation during peritoneal repair using immortalized temperature-sensitive mesothelial cells (TSMCs) in chlorhexidine gluconate (CG)-induced peritoneal fibrosis rats. METHODS: Continuous-infusion pumps containing 8% CG were placed into the abdominal cavity for 21 days. After the removal of the pumps, the TSMCs were injected into the peritoneal cavity at Day 22 (Tx-1 group) or 29 (Tx-2 group). Morphological findings and mRNA expressions of regeneration-related factors were examined at Days 22, 29 and 35. RESULTS: Peritoneal thickness was aggravated in the Tx-1 group. Levels of transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 mRNA in the Tx-1 group at Day 35 were comparable with those at Day 22. The levels of Snail, B-Raf and ERK-1, markers of epithelial to mesenchymal transition and of the RAS/MAPK pathway in the Tx-1 group, were significantly higher than those in the Tx-2 group. TGF-β and VEGF were produced from the transplanted mesothelial cells and the surrounding cells in the Tx-1 group. CONCLUSION: It appears that the paracrine effect of transplanted mesothelial cells during peritoneal repair is associated with its surrounding condition. It is important to determine the most appropriate time for developing peritoneal repair through mesothelial transplantation.