Introduction:Tissue-engineering techniques have been utilized to generate a prototype neointestine. The aim of this study was to characterize the neointestinal morphology and topography of enterocyte proliferation and apoptosis in the neomucosa of the tissue-engineered intestine.
Methods: Biodegradable polymers seeded with neonatal rat intestinal organoid units were implanted in adult rats to form neointestinal cysts. Five weeks after implantation, five of the rats underwent a side-to-side cyst-jejunal anastomosis. All rats were sacrificed at 6 months. Morphology, epithelial cell proliferation (Br-dU immunohistochemistry) and apoptotic rates (TUNEL assay) were assessed for native jejunal (Jej) and non-anastomosed (N-N) and anastomosed (A-N) neointestinal tissues. Groups were compared using ANOVA.
Results: A-N neomucosa consisted of folds resembling native jejunal crypts and villi, whereas N-N neomucosa was poorly developed. the anastomosis was patent in 80% of the rats at 6 months. Neomucosal epithelial proliferation was confined to the lower third of the folds. Apoptosis was evenly distributed throughout the epithelium (see Table).
Conclusions: These results suggest that the tissue engineered neomucosa can regenerate structural and dynamic features of the normal jejunum. Anastomosis to the native intestine is an essential step for the development of the neomucosa. Tissue engineering may represent a novel approach to the treatemnt of patients suffering from short bowel syndrome.
Mucosal thickness Muscle thickness Br-dU rate(%) Apoptotic rate (%)
Jej 551.4±12.5 117.0±5.3 47.3±2.7 0.87±0.23
N-N 102.5±83.7* 537±171.8* 32.1±16.2 0.46±0.46
A-N 538.9±95.7 358.2±34.0* 60.5±4.7 0.77±0.18
*p<0.05 compared to Jej p<0.05 compared to N-N
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