Conclusions
The autologous transplantation of multilayered fibroblast sheets significantly prevented PF and protected the pancreas, underscoring the potential utility of this approach for POPF prevention.
Methods
We developed a pancreatic fistula (PF) model of rat with transection of the splenic duct and surrounding pancreatic parenchyma. Multilayered fibroblast sheets prepared from tails were autologously transplanted to this model. The preventive effect was biochemically and histologically evaluated by measuring the ascitic levels of pancreatic enzymes and conducting immunohistochemistry and real-time polymerase chain reaction analyses of pancreatic tissue. Findings were compared to those obtained with acellular materials simply sealing the wound.
Results
In the PF model, the ascitic levels of pancreatic enzymes were transiently up-regulated. Inflammation and necrosis were histologically observed in a wide range. Islets were damaged even in remote areas. Transplantation of multilayered fibroblast sheets dramatically reduced the ascitic leakage of enzymes, suppressed inflammation, and broadly preserved the islets. Compared with acellular materials, these sheets offered superior prevention of cellular activity through the spaciotemporal regulation of fibrosis and angiogenesis. Notably, the leakage hole appeared to have been plugged with the fibrotic matrix, which might have been the most crucial mechanism minimizing pancreatic damage. Conclusions: The autologous transplantation of multilayered fibroblast sheets significantly prevented PF and protected the pancreas, underscoring the potential utility of this approach for POPF prevention.