Nutrition in Short-Bowel Syndrome

Ladefoged, Karin; Hessov, I; Jarnum, S.

doi:10.3109/00365529609094567

Cited by 32 publications

(13 citation statements)

References 68 publications

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“…In humans, the issue of intestinal lengthening becomes clinically important in patients with short bowel syndrome (Ladefoged et al, 1996). This condition most often occurs when a section of intestine is surgically removed postnatally for a variety of conditions in which a portion of the small intestine is no longer viable (Nightingale and Lennard-Jones, 1993).…”

Section: Introductionmentioning

confidence: 99%

Fgf9 signaling regulates small intestinal elongation and mesenchymal development

et al. 2008

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Short bowel syndrome is an acquired condition in which the length of the small intestine is insufficient to perform its normal absorptive function. Current therapies are limited as the developmental mechanisms that normally regulate elongation of the small intestine are poorly understood. Here, we identify Fgf9 as an important epithelial-to-mesenchymal signal required for proper small intestinal morphogenesis. Mouse embryos that lack either Fgf9 or the mesenchymal receptors for Fgf9 contained a disproportionately shortened small intestine, decreased mesenchymal proliferation, premature differentiation of fibroblasts into myofibroblasts and significantly elevated Tgfβ signaling. These findings suggest that Fgf9 normally functions to repress Tgfβ signaling in these cells. In vivo, a small subset of mesenchymal cells expressed phospho-Erk and the secreted Tgfβ inhibitors Fst and Fstl1 in an Fgf9-dependent fashion. The p-Erk/Fst/Fstl1-expressing cells were most consistent with intestinal mesenchymal stem cells (iMSCs). We found that isolated iMSCs expressed p-Erk, Fst and Fstl1, and could repress the differentiation of intestinal myofibroblasts in co-culture. These data suggest a model in which epithelial-derived Fgf9 stimulates iMSCs that in turn regulate underlying mesenchymal fibroblast proliferation and differentiation at least in part through inhibition of Tgfβ signaling in the mesenchyme. Taken together, the interaction of FGF and TGFβ signaling pathways in the intestinal mesenchyme could represent novel targets for future short bowel syndrome therapies.

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Section: Introductionmentioning

confidence: 99%

Fgf9 signaling regulates small intestinal elongation and mesenchymal development

et al. 2008

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“…[1][2][3] Although less common, SBS is also seen in adults suffering from Crohn's disease or from mesenteric infarction. 4,5 Intestinal failure from SBS generally occurs with loss of approximately 50%-75% of the small intestine. [6][7][8] The insufficient quantity of surface absorption results in a broad diversity of metabolic and physiologic disturbances, including fluid, nutrient, and weight loss.…”

mentioning

confidence: 99%

A Multicellular Approach Forms a Significant Amount of Tissue-Engineered Small Intestine in the Mouse

Sala

Matthews

Speer

et al. 2011

Tissue Engineering Part A

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Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection. In this study, we transitioned the technique to a mouse model, allowing investigation of the processes involved during TESI formation through the transgenic tools available in this species. This is a necessary step toward applying the technique to human therapy. Multicellular organoid units were derived from small intestines of transgenic mice and transplanted within the abdomen on biodegradable polymers. Immunofluorescence staining was used to characterize the cellular processes during TESI formation. We demonstrate the preservation of Lgr5-and DcamKl1-positive cells, two putative intestinal stem cell populations, in proximity to their niche mesenchymal cells, the intestinal subepithelial myofibroblasts (ISEMFs), at the time of implantation. Maintenance of the relationship between ISEMF and crypt epithelium is observed during the growth of TESI. The engineered small intestine has an epithelium containing a differentiated epithelium next to an innervated muscularis. Lineage tracing demonstrates that all the essential components, including epithelium, muscularis, nerves, and some of the blood vessels, are of donor origin. This multicellular approach provides the necessary cell population to regenerate large amounts of intestinal tissue that could be used to treat short bowel syndrome.

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“…Patienten mit einem komplizierten Morbus Crohn sind heute am meisten betroffen (50 ± 60 %). In früheren Jahren waren es mehr Patienten mit Mesenterialinfarkt [3,4]. Die häufigsten Ursachen sind in l " Tab.…”

Section: Ursachen Anatomische Und Pathosphysiologische Aspekteunclassified