O1033: Spring-mediated Distraction Enterogenesis Alters the Course of Adaptation in Porcine Small Bowel Syndrome

Saturday, October 8, 2022

1:50 PM – 2:05 PM US PDT

Location: H0154: Section on Neonatal-Perinatal Medicine

Background: Short bowel syndrome (SBS) results in inadequate small intestinal (SI) surface area with current therapies focused on medical and surgical management. Distraction enterogenesis uses mechanical force to increase length and stimulate growth of SI. Specifically, an intraluminal self-expanding spring provides mechanical force for elastic tissue, lengthening the bowel and triggering cellular proliferation and growth. This study aimed to characterize the adaptive response of the layers of SI to SBS and how spring-mediated distraction enterogenesis may alter the course of adaption to SBS.

Methods: Juvenile Yucatan pigs underwent laparotomy to remove 75% of SI to simulate SBS. 30-days post-bowel resection, intraluminal springs were placed, and native SI obtained. SI segments (native, spring-associated) were retrieved 60 days from resection and 30 days following spring insertion. Antibody staining defined muscularis layers (desmin), total epithelium length (CDH1), crypt (CD10-CDH1), and villus (CD10) heights. mRNA expression levels of epithelial cell types were also measured.

Results: SBS led to an initial adaptive response in all layers of the muscularis, including longitudinal, circular, mucosa, and serosal (p < 0.01). Total epithelium length (crypt+villus) also increased but was primarily composed of increased crypt height and decreased villus length (p < 0.01). While the adaptive changes seen in the muscularis layers reversed by 60-days post-resection, crypt height continued to increase while villi height decreased (p < 0.01). 30-days post-spring placement, spring-associated tissue showed enhanced growth of muscularis layers compared to SI distal to spring placement. Similarly, spring-associated total epithelial length was dramatically enhanced with a significant increase in crypt height but unchanged villi length. Response within the epithelium showed decreased expressions of enterochromaffin (EC), Goblet (GC), and Paneth cells, which only occurred during the initial phase of adaption. Intestinal stem cells did not significantly increase until 60 days post-resection in native tissue but were significantly increased in spring-associated tissue (p < 0.01). Compared to the adaptive response in native tissue, spring-associated tissue showed higher expression of EC and GC but a similar decrease in Paneth cells.

Conclusion: Our data showed that SBS resulted in an initial adaptive response within the muscularis and epithelium that plateaued and reversed in prolonged adaptive processes. Spring-mediated distraction enterogenesis changed the attenuation in the prolonged adaptive response seen in all structures except the villus, which decreased. This data improves our understanding of the morphological and cellular changes in SBS in a large animal model and illustrates the immediate changes induced by spring-mediated distraction enterogenesis.

Presenting Author(s)

Geoanna Bautista, MD

Assistant Professor of Pediatrics-Neonatology
University of California, Davis
University of California, Davis
Sacramento, California

Co-Author(s)

GD

Genia Dubrovsky, MD

Resident
University of California, Los Angeles
Los Angeles, California
NM

Nicolle Martin, n/a

PhD student
University of California, Davis
Davis, California
RS

RS Solorzano-Vargas, n/a

Staff Research Associate
University of California, Los Angeles
Los Angeles, California

Senior Author(s)

MM

Martin Martin, Martin, MD

Professor of Pediatrics, Gastroenterology
University of California, Los Angeles
Los Angeles, California
James Dunn, MD, PhD

Professor of Surgery, Pediatrics
Stanford University
Stanford University
Palo Alto, California