Abstract
Exocrine pancreatic insufficiency, caused by disease-induced loss of pancreatic exocrine cells, may be treated through regenerative stem cell technologies that facilitate the production of pancreatic exocrine cells from induced pluripotent stem cells (iPSCs). However, delivering the digestive enzymes produced in the transplanted cells to the gastrointestinal tract remains a challenge. To generate an allogenic transplantation rat model, minced pancreas was transplanted into the gastric submucosal space with ablation of muscularis mucosa. In the allogenic transplantation, transplanted pancreatic cells were engrafted. Elevated amylase was detected in gastric juice, while transplanted cells disappeared through auto-digestion when the muscularis mucosa was not eliminated. Human iPSCs were differentiated into pancreatic exocrine cells by stage-specific treatment with growth factors and chemical compounds, and the differentiated pancreatic cells were implanted into the gastric submucosal space of nude rats. The transplanted cells were engrafted, and amylase was detected in the gastric juice in some cases. These findings suggest that transplantation of pancreatic exocrine cells into the gastric submucosal space with muscularis mucosa elimination will contribute to a regenerative approach for pancreatic exocrine insufficiency.
Highlights
Exocrine pancreatic insufficiency is characterised by maldigestion and poor nutrition due to the insufficiency of pancreatic digestive enzymes
We generated an allogeneic transplantation model of rat pancreatic exocrine tissue transplanted into the gastric submucosal space to achieve functional transplantation
A high amount amylase was detected in the gastric juices in rats after transplantation and secretin and carbachol stimulation, which significantly increased the amount of amylase in the gastric juice (Fig. 1f). These findings suggested that the transplantation of pancreatic cells with muscularis mucosa elimination through the gastric ulcer healing process might enable the fabrication of functional pancreatic exocrine tissues
Summary
Exocrine pancreatic insufficiency is characterised by maldigestion and poor nutrition due to the insufficiency of pancreatic digestive enzymes. Many studies have already reported the recovery of pancreatic endocrine function by the transplantation of allogeneic pancreatic cells in the clinical setting and human pluripotent stem cell-derived pancreatic cells in animal models. There are few reports on the recovery of pancreatic exocrine function by the cell replacement approach possibly because of several issues including the transplantation site restriction and outflow tract of pancreatic enzymes. When transplanting pancreatic exocrine tissue into a patient with pancreatic exocrine insufficiency, pancreatic digestive enzymes produced in the transplanted tissue must be secreted into the upper gastrointestinal tract to achieve effective digestion[12]. Www.nature.com/scientificreports methods of transplantation of pancreatic exocrine cells to achieve functionally appropriate delivery of pancreatic digestive enzymes from the transplanted tissue into the gastrointestinal tract. We generated an allogeneic transplantation model of rat pancreatic exocrine tissue transplanted into the gastric submucosal space to achieve functional transplantation. We observed the engraftment of the iPSC-derived exocrine cells in the gastric submucosal space of rat
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