Type: report
Abstract: The small intestine is the primary site for nutrient absorption.Extensive small intestinal resection leads to inadequate digestion and malabsorption, a condition known as short bowel syndrome (SBS).Intestinal transplantation is currently the only potentially-curative treatment option for severe SBS patients, but severe allogenic reaction reduces the graft survival rate and has prevented the widespread use this treatment.Therefore, development of a novel therapeutic strategy for SBS is warranted.The structural complexity of the small intestine has precluded the application of organoid-based regenerative medicine to small intestinal diseases.To establish a clinically relevant therapeutic strategy for SBS by means of colon epithelial conversion using small intestinal organoids, we elected to use a rat SBS model for their tractability.First, we successfully confirmed that preserving a short length of the ileum prevents intestinal failure in the rat SBS model, which is consistent with the clinical presentation of human SBS.To label donor organoids, we used small intestinal organoids derived from Lewis luciferase transgenic rats.EDTA-based breaching in combination with surgery enabled the removal of the rat colonic epithelium, and careful optimizations allowed us to overlay epithelium-depleted rat colon with small intestinal organoids.Ileum organoid-transplanted SBS rats exhibited milder body weight loss and significantly higher survival rate compared to colon organoid-transplanted rats.Furthermore, we confirmed a formation of LYVE-1+ lacteal-like structure equipped with the absorption-related machinery in ileum organoid-transplanted tissues.
Author: 杉本, 真也
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7145322648