A Rat Graft Rejection Model of Intestinal Transplantation with Exteriorized Ileostomy for Longitudinal Prognosis Assessment.

Abstract

To date, organ transplantation remains the mainstream treatment for organ failure. Among various solid organs, patient prognosis following intestinal transplantation remains unsatisfactory, primarily due to graft rejection. This challenge necessitates further improvement in surgical techniques or the development of novel post-surgical pharmacological interventions. This article presents a rat model of intestinal transplantation graft rejection to serve as a platform for such investigations. A segment of the ileum isolated from the Fischer 344 (F344) strain was allografted to a Lewis (LEW) rat, followed by administration of tacrolimus at a defined dose and schedule. An exteriorized ileostomy was constructed to allow non-invasive, longitudinal monitoring of the tissue status of the allograft. A trichromatic linear regression model was trained using ileostomy images and used to construct an image-based assessment scheme capable of evaluating ileostomy status on a scale from 0 to 10. Evaluation indicated allograft health deterioration beginning in the third week after transplantation. Histological analyses of the allograft confirmed signs of chronic rejection from post-operative day (POD) 28 onward, similar to those observed in human patients, and validated the results of the non-invasive ileostomy image assessment. The intestinal allograft model and associated assessment methods presented here are expected to facilitate treatment development for intestinal transplantation.