Intestinal Stem Cell Organoid Transplantation Generates Neomucosa in Dogs

Abstract

Background and Aims Intestinal stem cell organoid transplantation generates functional intestinal neomucosa and has been used therapeutically to improve nutrient absorption and cure bile acid malabsorption in rats. We hypothesized that intestinal organoids can be harvested and transplanted to generate intestinal neomucosa in a large animal model. Materials and Methods In group 1, 2-month old beagles (n=6) underwent autotransplantation of intestinal organoids prepared from a segment of their own ileum. In group 2, intestinal organoids were harvested from fetuses and allotransplanted into 10-month old mother animals (n=4). Tissues were harvested after 4 weeks and analyzed by hematoxylin and eosin histology and fluorescent microscopy. Results Large numbers of viable organoids were harvested in both groups. In group 1, no neomucosal growth was identified in any of the engraftment sites after autotransplantation of juvenile organoids. In group 2, neomucosal growth with large areas of crypts and villi was identified in 11 of 12 polyglycolic acid scaffolds after allotransplantation of fetal organoids. The neomucosa resembled normal canine mucosa in structure and composition. Conclusions Intestinal stem cell organoid transplantation can be used to generate neomucosa in dogs. This is the first report of successful generation of intestinal neomucosa using intestinal stem cell organoid transplantation in a large animal model.

Use of Collagen Gel as an Alternative Extracellular Matrix for the In Vitro and In Vivo Growth of Murine Small Intestinal Epithelium

“…3,4 Following the description of a novel method for their long-term in vitro culture, 5 there have been reports of successful culture of the various mucosal epithelia of murine stomach, murine colon, human small intestine, both benign and neoplastic human 1 colon, and human Barrett's esophagus. [6][7][8] Previous methods for in vivo implantation relied on initial isolation of stem cell clusters surrounded by neighboring mesenchyme, [9][10][11][12] whereas the current culture techniques appear to have obviated this requirement. 13 In vitro cultured small intestinal units have been variously termed enteroids, spheroids, and organoids by different groups.…”

Growth Factors Adsorbed on Polyglycolic Acid Mesh Augment Growth of Bioengineered Intestinal Neomucosa

“…Furthermore, TESI has been demonstrated in rats to reverse clinical malabsorption syndromes [7,9]. Recently, we have been the first to report the successful generation of intestinal neomucosa using organoid transplantation in a large animal model [10]. All described models of intestinal organoid transplantation are limited by a major problem that must be addressed in order to translate their success into a clinical application.…”

Intestinal Organoids—Current and Future Applications

“…The authors showed that the isolation and transplantation of 3Dcultured cells can be used to generate neomucosa in a dog model [43]. However the molecular characterization of the presumed "organoids" was not rigorously.…”