Application of Distractive Forces to the Small Intestine: Defining Safe Limits

Miyasaka, Eiichi; Okawada, Manabu; Utter, Brent; Mustafa-Maria, Haytham; Luntz, Jonathan; Brei, Diann; Teitelbaum, Daniel H.

doi:10.1016/j.jss.2010.03.060

Cited by 23 publications

(18 citation statements)

References 14 publications

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“…39 A critical consequence of SBS is loss of absorption area, so recent research has focused on increasing absorption area. 11,12,41,42 The use of growth factors may result in significant increase in bowel adaptation. 43 Using an implanted mechanical device in pigs, our laboratory demonstrated a far greater increase in adaptation than can be achieved with growth factors-nearly three-fold increase in small bowel length 12 In addition to lengthening of the bowel, epithelial cell FIG.…”

Section: Discussionmentioning

confidence: 99%

Distraction-Induced Intestinal Growth: The Role of Mechanotransduction Mechanisms in a Mouse Model of Short Bowel Syndrome

Sueyoshi

Ignatoski

Okawada

et al. 2013

Tissue Engineering Part A

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Novel strategies are needed to address the problem of patients with short bowel syndrome. We previously demonstrated a three-fold lengthening of pig bowel after 2 weeks of applied distractive forces, but we have not elucidated the mechanisms facilitating this growth. We used a mouse model of distraction-induced enterogenesis. High molecular weight polyethylene glycol (PEG) osmotically stretched an isolated small bowel segment (PEG-stretch). Significant increases in villus height and crypt depth and in intestinal epithelial cell length and numbers suggested epithelial remodeling in addition to proliferation during enterogenesis. LC-MS/ MS analysis showed a two-fold upregulation of a-actinin-1 and -4. We also demonstrated that p-focal adhesion kinase (FAK), FAK, a-actinin, and Rac1 were significantly upregulated and that F-actin was relocalized in PEGstretch versus controls. Blockade of the phosphotidyl inositol 3¢ kinase pathway failed to influence the increase in proliferation or decline in apoptosis after stretch, suggesting alternative signaling pathways are used, including MEK and P38MAPK, which were both upregulated during enterogenesis. Our data suggests that several known mechanotransduction pathways drive distraction-induced enterogenesis.

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Section: Discussionmentioning

confidence: 99%

Distraction-Induced Intestinal Growth: The Role of Mechanotransduction Mechanisms in a Mouse Model of Short Bowel Syndrome

Sueyoshi

Ignatoski

Okawada

et al. 2013

Tissue Engineering Part A

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“…As we and others have previously shown, distraction enterogenesis produces significant, sustained intestinal lengthening with preservation of intestinal function [11][12][13]. This is characterized by mesenteric neovascularization, increased villus height and crypt depth, muscular hypertrophy, and increased epithelial cell proliferation [9,14,15].…”

Section: Introductionmentioning

confidence: 85%

A novel double-balloon catheter device for fully endoluminal intestinal lengthening

et al. 2014

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“…In a paper by Miyasaka et al, the optimal force on human intestine was determined by measuring blood flow to the intestine via Doppler [31]. In this study, the authors first performed ex vivo experiments on pig small intestine to determine maximal limits of the distractive force, which could be applied.…”

Section: Challenges In Experimental Designmentioning

confidence: 99%

“…In contrast, at the ends of the bowel segments where the expanding device abuts the wall directly, a substantial decrease in blood flow was noted at 100 gram-force. Thus, the optimal experimental force was determined to be approximately 100 gram-force [31]. This information is critical in setting parameters for experimental design.…”

Section: Challenges In Experimental Designmentioning

confidence: 99%

Mechanical Enterogenesis ‐ A Review

Stark¹,

Dunn²

2012

Journal of Healthcare Engineering

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Mechanical enterogenesis is a novel method of lengthening pre-existing intestine with distractive force. The application of mechanical force on small intestine aims to induce cellular proliferation and ultimately increase bowel length. This has been investigated primarily for the treatment of short bowel syndrome (SBS). Research has been ongoing for well over a decade in this arena and a multitude of advances have been made, both in the understanding of the biology behind force induced cellular proliferation and in the basic mechanics of force delivery systems. Important experimental models have been developed for studying this phenomenon and the collaboration of engineers and medical researchers has lead to the design of several devices that successfully lengthen small intestine. This has catapulted the field forward and there may soon be a device suitable for medical use in humans. This review analyses the past, present and future of mechanical enterogenesis.

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Application of Distractive Forces to the Small Intestine: Defining Safe Limits

Abstract: Background-Distraction enterogenesis is a novel method for increasing small bowel length by the application of linearly directed forces. However, the magnitude of distractive forces that human and animal small bowel can safely withstand is unknown.

Cited by 23 publications

References 14 publications

Distraction-Induced Intestinal Growth: The Role of Mechanotransduction Mechanisms in a Mouse Model of Short Bowel Syndrome

Distraction-Induced Intestinal Growth: The Role of Mechanotransduction Mechanisms in a Mouse Model of Short Bowel Syndrome

A novel double-balloon catheter device for fully endoluminal intestinal lengthening

Mechanical Enterogenesis ‐ A Review

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