A novel model for simultaneous study of neointestinal regeneration and intestinal adaptation

Abstract

The use of autologous grafts, fabricated from tissue-engineered neointestine, to enhance insufficient compensation of intestinal adaptation for severe short bowel syndrome is a compelling idea. Unfortunately, current approaches and knowledge for neointestinal regeneration, unlike intestinal adaptation, are still unsatisfactory. Thus, we have designed a novel model of intestinal adaptation with simultaneous neointestinal regeneration and evaluated its feasibility for future basic research and clinical application. Fifty male Sprague-Dawley rats weighing 250-350 g underwent this procedure and sacrificed at 4, 8, and 12 weeks postoperatively. Spatiotemporal analyses were carried out by gross, histology, and DNA/protein quantification. Three rats died of operative complications. In early experiments, the use of hard silicone stent as tissue scaffold in 11 rats was unsatisfactory for neointestinal regeneration. In later experiments, when a soft silastic tube was used, the success rate increased up to 90.9%. Further analyses revealed that no neointestine developed without donor intestine; regenerated lengths of mucosa and muscle were positively related to time postsurgery but independent of donor length with 0.5 or 1 cm. Other parameters of neointestinal regeneration or intestinal adaptation showed no relationship to both time postsurgery and donor length. In conclusion, this is a potentially important model for investigators searching for solutions to short bowel syndrome.

Postembryonic Organogenesis of the Digestive Tube

“…However, application of this procedure is limited by donor availability, high incidence of graft rejection, toxicity of immune suppression, and relatively low success rates (Howell & Wells, 2011). Although alternative approaches involving tissue engineering are being actively sought, their development is at its infancy as their progress heavily depends on still incomplete fundamental biological knowledge of how to stimulate visceral regeneration in mammals at the whole-organ level (Chen & Beierle, 2004; Gupta et al, 2006; Howell & Wells, 2011; Jwo et al, 2013; Levin & Grikscheit, 2012; Ross et al, 2013). …”

Identifying the Growth Factors for Improving Neointestinal Regeneration in Rats through Transcriptome Analysis Using RNA-Seq Data

“…In this study, we used next generation RNA sequencing (RNA-Seq) and bioinformatics analyses to explore transcriptome changes in neoregeneration and adaptation tissue and to identify key growth factors affecting regeneration and adaptation of intestinal tissue. Our previous research reveals complex growth factor regulation in small intestine regeneration and adaptation [1] and provides potential applications in tissue engineering by introducing key growth factors identified here into the injury site. For this study we focused on our earlier research involving simultaneous intestinal adaptation and neointestinal regeneration in individual rats [1].…”

“…Our previous research reveals complex growth factor regulation in small intestine regeneration and adaptation [1] and provides potential applications in tissue engineering by introducing key growth factors identified here into the injury site. For this study we focused on our earlier research involving simultaneous intestinal adaptation and neointestinal regeneration in individual rats [1].…”

“…Our surgical model of simultaneous intestinal adaptation and neointestinal regeneration in individual rats was evaluated previously for its feasibility for future basic research and clinical application. There, a soft silastic tube was used as a tissue scaffold stent for neointestinal regeneration [1]. This model greatly reduces interexperimental variation and simplifies data interpretation.…”

“…This model greatly reduces interexperimental variation and simplifies data interpretation. To facilitate neointestinal regeneration as well as have higher quality regenerative tissues, we aimed to understand the neointestinal regeneration mechanisms and then explore the biological functions of newly identified regeneration-related molecules in our rat model [1].…”