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11. A pilot study investigating a novel subcutaneously implanted pre-cellularised scaffold for tissue engineering of intestinal mucosa

Author

Lloyd, D. A. J., Ansari, T. I., Gundabolu, P., Shurey, S., Maquet, V., Sibbons, P. D., Boccaccini, A. R., and Gabe, S. M.

Subjects
Scaffold, lcsh:Diseases of the musculoskeletal system, lcsh:Surgery, Tissue engineering, Angiogenesis, lcsh:RD1-811, lcsh:RC925-935, tissue engineering, scaffold, intestine, angiogenesis, NATIVE SMALL-BOWEL, ANASTOMOSIS, NEOINTESTINE, Intestine
Abstract

Tissue engineering of the small intestine offers an alternative to long-term intravenous nutrition and transplantation in patients with intestinal failure. Initial work, although encouraging, is limited by the volume of neonatal tissue required to produce a small neomucosal cyst. Our novel approach is to implant tubular poly-lactide-co-glycolide (PGLA) foam scaffolds subcutaneously. The aim of this study was to investigate whether these scaffolds would support growth of intestinal neomucosa. PGLA scaffolds were implanted subcutaneously into 8 Lewis rats; after 5 weeks, 'organoid units' were injected into the lumens. Tissue was assessed histologically after harvesting and quantitative immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGF-R2), fibroblast growth factor basic (bFGF) and fibroblast growth factor receptor 2 (FGF-R2). At 4 weeks post organoid unit implantation, clearly recognisable mucosa and submucosa was present on the luminal surface of the scaffold. Densities of VEGF and VEGF-R2 positive cells increased with time post organoid unit implantation. This pilot study demonstrates that it is possible to tissue engineer small intestinal neomucosa using subcutaneously implanted PLGA scaffolds. The yield of the process compares favourably to the published literature. Further work is required to optimise the technique.

Published
2006

19. Recent experience of adult small-intestinal and multi-visceral transplantation at Addenbrooke's Hospital, Cambridge University, UK

Author

Wiles, A., primary, Butler, A., additional, Tincknell, H., additional, Duncan, S., additional, Chukualim, B., additional, Gabe, S. M., additional, Gibbs, P., additional, Jamieson, N. V., additional, Praseedom, R. K., additional, Watson, C. J., additional, Woodward, J. M., additional, and Middleton, S. J., additional

Published
2010
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35. Indications and outcomes of home parenteral nutrition in patients with an ileoanal pouch.

Author

Oke SM, Segal J, Clark SK, Hart AL, and Gabe SM

Subjects
Female, Humans, Male, Proctocolectomy, Restorative, Retrospective Studies, Treatment Outcome, Colonic Pouches, Parenteral Nutrition, Home
Abstract

Introduction: Restorative proctocolectomy is a surgical treatment for patients with medically refractory ulcerative colitis and some cases of familial adenomatous polyposis. Intestinal failure, defined as an inability to maintain adequate hydration and micronutrient balances when on a conventionally accepted normal diet, is a rare complication of restorative proctocolectomy. We describe our experience of patients with restorative proctocolectomy who have developed intestinal failure requiring parenteral support., Material and Methods: This was a retrospective analysis using a database of patients referred to our intestinal failure unit from January 1998 to January 2016. We analysed the records of all those patients who had restorative proctocolectomy who developed intestinal failure., Results: 807 patient records analysed, 35 patients were found to have had a restorative proctocolectomy (13 male and 22 female). Ninety-one percent (n = 32) of patients developed IF as a consequence of unpredictable complications which occurred after RPC formation. Potentially predictable complications were noted in 9% (n = 3) of patients., Discussion and Conclusions: Most cases of intestinal failure in restorative proctocolectomy were unpredictable. In a small number of patients, accurate assessment and measurement of the small intestine may have better predicted the adverse outcome of intestinal failure allowing improved pre-operative counseling of patients.

Published
2019
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36. The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans.

Author

Gabe SM, Bjarnason I, Tolou-Ghamari Z, Tredger JM, Johnson PG, Barclay GR, Williams R, and Silk DB

Subjects
Adolescent, Adult, Decarboxylation, Female, Humans, Intestinal Mucosa metabolism, Keto Acids metabolism, Liver Transplantation, Male, Middle Aged, Mitochondria drug effects, Mitochondria metabolism, Permeability, Energy Metabolism drug effects, Immunosuppressive Agents pharmacology, Intestines drug effects, Tacrolimus pharmacology
Abstract

Background & Aims: The maintenance of the intestinal mucosal barrier may be energy dependent. Tacrolimus is a potent immunosuppressive drug that decreases mitochondrial adenosine triphosphate production and increases intestinal permeability in animals., Methods: Twelve liver graft recipients receiving tacrolimus, 9 healthy volunteers, and 5 liver graft recipients not receiving immunosuppression underwent a combined absorption-permeability-mitochondrial function test using 5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O-methyl-D-glucose, 1 mg/kg 2-keto[1-13C]isocaproic acid ([13C]KICA), and 20 mg/kg L-leucine. The respiratory quotient and resting energy expenditure were measured by indirect calorimetry. Tacrolimus pharmacokinetic profiles and levels of endotoxin and IgM and IgG endotoxin core antibodies were determined., Results: Tacrolimus inhibited the decarboxylation of [13C]KICA, the resting energy expenditure, and the respiratory quotient in an exposure-dependent manner, suggesting an inhibition of mitochondrial respiration. Tacrolimus inhibited intestinal absorptive capacity in an exposure-dependent manner. Tacrolimus-treated patients had an increased intestinal permeability and significantly higher endotoxin levels compared with healthy volunteers., Conclusions: Tacrolimus inhibits cellular energy production in humans at clinically relevant doses. This is associated with an increased intestinal permeability, endotoxemia, and an impaired intestinal absorptive capacity.

Published
1998
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