Retracing our STEPs: Four decades of progress in intestinal lengthening procedures for short bowel syndrome

Greig, Chasen J.; Oh, Pilyung S.; Gross, Erica R.; Cowles, Robert A.

doi:10.1016/j.amjsurg.2018.11.025

Cited by 14 publications

(6 citation statements)

References 68 publications

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“…However, guts do not display compensatory lengthening postnatally, either after injury or congenital defects that cause shortening. Consequently, individuals with short bowel syndrome do not recover intestinal length over time, leading to chronic water and nutrient absorption deficits 86 . Interestingly, application of longitudinal mechanical force can promote postnatal intestinal growth in animal models 2 .…”

Section: Discussionmentioning

confidence: 99%

Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation

et al. 2021

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How tubular organs elongate is poorly understood. We found that attenuated ciliary Hedgehog signaling in the gut wall impaired patterning of the circumferential smooth muscle and inhibited proliferation and elongation of developing intestine and esophagus. Similarly, ablation of gut-wall smooth muscle cells reduced lengthening. Disruption of ciliary Hedgehog signaling or removal of smooth muscle reduced residual stress within the gut wall and decreased activity of the mechanotransductive effector YAP. Removing YAP in the mesenchyme also reduced proliferation and elongation, but without affecting smooth muscle formation, suggesting that YAP interprets the smooth muscle-generated force to promote longitudinal growth. Additionally, we developed an intestinal culture system that recapitulates the requirements for cilia and mechanical forces in elongation. Pharmacologically activating YAP in this system restored elongation of cilia-deficient intestines. Thus, our results reveal that ciliary Hedgehog signaling patterns the circumferential smooth muscle to generate radial mechanical forces that activate YAP and elongate the gut.

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Section: Discussionmentioning

confidence: 99%

Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation

et al. 2021

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“…Notably, the digestive disorders are related to intestinal dysfunction ( Johnson, 1985 ; Soybel, 2005 ; Iji, 2008 ). Besides, the length of the digestive tract is positively correlated with nutrient absorption, while the decreases in the digestive tract length may limit the basic metabolism and nutrient availability of the body ( Ortigues and Doreau, 1995 ; Greig et al, 2019 ). As reported by several authors, a consequence of the smaller digestive tract is reduced feed intake capacity ( Clinquart et al, 1995 ; Fiems et al, 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Viscera Characteristics of MSTN-Edited Heterozygous Pigs

Pei

Fan²,

Song³

et al. 2022

Front. Genet.

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Myostatin (MSTN) is a protein that negatively regulates growth of skeletal muscle, and inactivation of MSTN improves the mass of skeletal muscle. Our previous work found that MSTN+/− pigs have higher muscle depth and lower fat depth compared to wild type without any developmental problems. Therefore, MSTN-edited pigs are most likely to appear as heterozygotes in the potential future market, but the characteristics of organs in digestive and reproductive system of pigs with MSTN gene editing remains unclear. Here, we investigated the histological of the organs in the digestive system and reproductive system in MSTN gene heterozygotes at adult stages. The length of intestine was further compared between adult heterozygous and wild type pigs. We found no significant differences in histomorphology of organs, including heart, duodenum, jejunum, ileum, cecum, colon, testis, epididymis, ovaries, oviducts and uterus, between individuals from two genotypes. Moreover, there was no significant difference in the average length of intestine in adult pigs. Our data provide a reference for further clarifying the applications of MSTN gene edited pigs.

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“…For this reason, intestinal lengthening procedures are, therefore, an interesting approach to SBS. They are basically represented by Bianchi’s and by the STEP procedures [ 11 , 12 , 42 , 43 ]. Both methods can double the bowel’s length, but this goes to the detriment of the diameter that is usually halved, leaving the net absorption area unchanged.…”

Section: Discussionmentioning

confidence: 99%

Evidence of glucose absorption in a neoformed intestine

et al. 2022

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Recent advances in the field of tissue regeneration are offering promising therapeutic options for the treatment of short bowel syndrome. This study aimed to evaluate the glucose absorptive capacity of a neoformed intestine obtained from a biological scaffold in a rodent model and the steadiness of the engrafted segment area. Twenty-four male Sprague–Dawley rats were used for this study. Under anesthesia, a patch of biological material (2.2 × 1.5 cm) was engrafted in the anti-mesenteric border of the small bowels of 12 rats. Twelve rats were sham-operated. Animals were studied at 4, 8, and 10 months postengraftment. Functional and histological analyses were performed. The functional analysis was performed using an 18F-FDG analog as a probe and the results were acquired with an optical imager. The intensity of the fluorescent signal emitted by the neointestine was comparable with that emitted by the native intestine in all animals and was visible after injection in the preserved mesentery. The mean intestinal volume at time of engraftment and after 10 months was 4.08 cm3 (95% CI [3.58–4.58]) and 3.26 cm3 (CI 95% [3.23–3.29]), respectively, with a mean shrinkage of 17.3% (range 10.6–23.8%), without any evidence of stenosis. Morphological analysis revealed the progression of the biological material toward a neoformed intestine similar to the native intestine, especially at 8 and 10 months. In a rodent model, we demonstrated that a neointestine, obtained from a biological scaffold showed glucose absorption and a durable increase in diameter.

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Retracing our STEPs: Four decades of progress in intestinal lengthening procedures for short bowel syndrome

Cited by 14 publications

References 68 publications

Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation

Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation

Viscera Characteristics of MSTN-Edited Heterozygous Pigs

Evidence of glucose absorption in a neoformed intestine

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