Regenerative Capacity of the Enteric Nervous System after Ileoileal Anastomoses in a Rat Model

Pfeifle, Viktoria A.; Gros, Stephanie J.; Frongia, Giovanni; Schäfer, Karl‐Herbert; Holland‐Cunz, Stefan

doi:10.1055/s-0036-1586200

Cited by 3 publications

(1 citation statement)

References 16 publications

(17 reference statements)

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“…It would be interesting to explore the changes in epithelial parameters after surgical treatment of the intestinal obstruction. A study using a rat model has concluded that the enteric nervous system has a high regenerative capacity after anastomoses [24]. Confirmation of this experimental study with human newborns would be complicated due to the very limited availability of postoperative bowel samples, particularly of the distal segment, with potential ethical concerns.…”

Section: Plos Onementioning

confidence: 87%

Epithelial changes of congenital intestinal obstruction in a rat model

et al. 2020

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IntroductionIntestinal atresia is a rare congenital affliction that is often associated with severe bacterial infections despite adequate neonatal surgery. Previous studies have focused on enteric nervous system variations. We hypothesized that epithelial systems (ES) may also be involved in the pathophysiology of postnatal disorders. Materials and methodsGlobal gene expression was measured by transcriptomic analysis in a rat model of induced intestinal atresia. The analyses then focused on genes involved in ES (enterocytes and goblet cells). Rat fetus small intestines at various stages of development (ED15, ED17, ED19, and ED21, n = 22), were used as non-operated controls and compared to the upper and lower segments of rat fetus small intestines with an induced atresia (n = 14; ligature at ED18). The pattern of gene expression was then confirmed by histochemistry, electron microscopy, and RT-qPCR. ResultsFrom ED15 to ED21, the expression of several genes exhibited a physiological increase of ES markers, with a significant increase at the end of gestation. The operated embryos exhibited significantly higher variations of gene expression in the proximal segment than in the distal segment in terms of absorption and the epithelial barrier. An increase in goblet cells and markers was observed in the proximal segment compared to the controls. ConclusionFetal intestinal obstruction accelerates maturation in the proximal segment and disrupts the intestinal wall in the distal segment, with a decrease in the number of mucosal cells.

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Section: Plos Onementioning

confidence: 87%

Epithelial changes of congenital intestinal obstruction in a rat model

et al. 2020

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Building gut from scratch — progress and update of intestinal tissue engineering

Tullie

Jones

Coppi

et al. 2022

Nat Rev Gastroenterol Hepatol

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Short bowel syndrome (SBS), a condition defined by insufficient absorptive intestinal epithelium, is a rare disease, with an estimated prevalence up to 0.4 in 10,000 people. However, it has substantial morbidity and mortality for affected patients. The mainstay of treatment in SBS is supportive, in the form of intravenous parenteral nutrition, with the aim of achieving intestinal autonomy. The lack of a definitive curative therapy has led to attempts to harness innate developmental and regenerative mechanisms to engineer neo-intestine as an alternative approach to address this unmet clinical need. Exciting advances have been made in the field of intestinal tissue engineering (ITE) over the past decade, making a review in this field timely. In this Review, we discuss the latest advances in the components required to engineer intestinal grafts and summarise the progress of ITE. We also explore some key factors to consider and challenges to overcome when transitioning tissue engineered intestine towards clinical translation and provide the future outlook of ITE in therapeutic applications and beyond. BlurbIntestinal tissue engineering offers a potential therapeutic option for short bowel syndrome. This Review examines the progress in intestinal tissue engineering, discusses the components required for engineered intestinal grafts, preclinical progress and efforts towards clinical translation, including challenges to overcome. Key points• Intestinal tissue engineering has the potential to offer curative therapy for patients with short bowel syndrome • Multiple components, including an absorptive mucosa, smooth muscle, enteric nerves and vasculature are required to generate a functional full thickness intestinal graft• Advances in intestinal tissue engineering include endothelial cell reprogramming and vascular engineering, generation of mucosal grafts using patient-derived materials and colon mucosal repurposing using small intestinal organoids.• Vascularisation and lymphatic engineering, generation of multi-layered personalised intestinal grafts and scaling-up of graft size present some of the future challenges in

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Nobiletin restores HFD-induced enteric nerve injury by regulating enteric glial activation and the GDNF/AKT/FOXO3a/P21 pathway

Pang,

Zhang,

Zhong

et al. 2024

Mol Med

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Background To explore whether nobiletin has a protective effect on high-fat diet (HFD)-induced enteric nerve injury and its underlying mechanism. Methods An obesity model was induced by a HFD. Nobiletin (100 mg/kg and 200 mg/kg) and vehicle were administered by gastric gavage for 4 weeks. Lee’s index, body weight, OGTT and intestinal propulsion assays were performed before sacrifice. After sampling, lipids were detected using Bodipy 493/503; lipid peroxidation was detected using MDA and SOD kits and the expression of PGP 9.5, Trem2, GFAP, β-tubulin 3, Bax, Bcl2, Nestin, P75 NTR, SOX10 and EDU was detected using immunofluorescence. The GDNF, p-AKT, AKT, p-FOXO3a, FOXO3a and P21 proteins were detected using western blotting. The relative mRNA expression levels of NOS2 were detected via qPCR. Primary enteric neural stem cells (ENSCs) were cultured. After ENSCs were treated with palmitic acid (PA) and nobiletin, CCK-8 and caspase-3/7 activity assays were performed to evaluate proliferation and apoptosis. Results HFD consumption caused colon lipid accumulation and peroxidation, induced enteric nerve damage and caused intestinal motor dysfunction. However, nobiletin reduced lipid accumulation and peroxidation in the colon; promoted Trem2, β-tubulin 3, Nestin, P75NTR, SOX10 and Bcl2 expression; inhibited Bax and GFAP expression; reduced NOS2 mRNA transcription; and regulated the GDNF/AKT/FOXO3a/P21 pathway. Nobiletin also promoted PA-induced impairment of ENSCs. Conclusions Nobiletin restored HFD-induced enteric nerve injury, which may be associated with inhibiting enteric nerve apoptosis, promoting enteric nerve survival and regulating the GDNF/AKT/FOXO3a/P21 pathway.

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Regenerative Capacity of the Enteric Nervous System after Ileoileal Anastomoses in a Rat Model

Cited by 3 publications

References 16 publications

Epithelial changes of congenital intestinal obstruction in a rat model

Epithelial changes of congenital intestinal obstruction in a rat model

Building gut from scratch — progress and update of intestinal tissue engineering

Nobiletin restores HFD-induced enteric nerve injury by regulating enteric glial activation and the GDNF/AKT/FOXO3a/P21 pathway

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