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Delivery of pancreatic digestive enzymes into the gastrointestinal tract by pancreatic exocrine tissue transplant.

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.

SUBMITTER: Ito K

PROVIDER: S-EPMC6459827 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Delivery of pancreatic digestive enzymes into the gastrointestinal tract by pancreatic exocrine tissue transplant.

Ito Kyoji K Matsuura Katsuhisa K Mihara Yuichiro Y Sakamoto Yoshihiro Y Hasegawa Kiyoshi K Kokudo Norihiro N Shimizu Tatsuya T

Scientific reports 20190411 1

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 ...[more]

PMID: 30976035

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Project description:To investigate dietary protein level effects on digestive mechanisms, weaned piglets were fed for 45 d with diets containing 20%, 17%, or 14% crude protein (CP) supplemented to meet requirements for essential amino acids. This article describes the influence of dietary protein on gastrointestinal hormones and expression of an array of digestive enzymes in the gastrointestinal tract and pancreas. Results indicated that there were no significant differences in expression of enzymes involved in carbohydrate digestion, except for maltase in the duodenum. In the jejunum, amylase expression in pigs fed 20% CP was much higher than that in pigs fed other diets (P<0.05) and maltase expression in those fed 17% CP was higher than that in other treatments (P<0.05). Although there were no remarkable differences in expression of aminopeptidase in the small intestine or carboxypeptidase in the pancreas (P>0.05), there was a trend towards higher expression of various proteases in pigs fed 17% CP. The duodenal expression of enteropeptidase in diets with 14% and 17% CP was significantly higher than that with 20% CP (P<0.05), but treatment differences did not existed in jejunum (P>0.05). The expression of GPR93 as a nutrient-responsive G protein-coupled receptor in 14% and 17% CP diets was significantly higher than that in 20% CP diet in the small intestine (P<0.05). The expressions of genes for pancreatic enzymes, lipase and elastase, were significantly higher in pigs fed diets with low CP, while similar trends occurred for carboxypeptidase, chymotrypsin and amylase. Conversely, the gastric expressions of pepsinogen A and progastricsin were lower with the 17% CP diet. Differences between treatments were found in the gastric antral contents of cholecystokinin and somatostatin: both increased in pigs fed 17% CP, accompanied by decreased content of motilin, which was also seen in plasma concentrations. These patterns were not reflected in duodenal contents. In general, 17% dietary CP was beneficial to the digestion of nutrient substance in the gastrointestinal tract.

Dataset Information

Delivery of pancreatic digestive enzymes into the gastrointestinal tract by pancreatic exocrine tissue transplant.

Publications

Delivery of pancreatic digestive enzymes into the gastrointestinal tract by pancreatic exocrine tissue transplant.

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