Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine

Choi, Rosa; Riegler, Martin; Pothoulakis, Charbalos; Kim, Byung Soo; Mooney, David J.; Vacanti, Martin P.; Vacanti, Joseph P.

doi:10.1016/s0022-3468(98)90520-6

Cited by 99 publications

(60 citation statements)

References 12 publications

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“…TESI derived from autologous organ-specific stem cells is a possible therapy for tissue replacement following intestinal injury, resection, or congenital absence. TESI was first generated from syngeneic tissue in a rat model, transplanting organoid units (OU) into the momentum on a polymer scaffold (5). OUs are multicellular cell clusters derived from donor intestine and contain both mesenchymal and epithelial cells (9).…”

mentioning

confidence: 99%

Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function

Grant

Mojica

Sala

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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NC, Grikscheit TC. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function. Am J Physiol Gastrointest Liver Physiol 308: G664 -G677, 2015. First published January 8, 2015; doi:10.1152/ajpgi.00111.2014.-Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells. tissue engineering; regenerative medicine; intestinal failure; intestinal stem cell; short bowel syndrome PATIENTS WITH INTESTINAL FAILURE (IF) lose nutritional autonomy secondary to a broad range of metabolic and physiological disturbances, including fluid, nutrient, and weight loss secondary to insufficient intestinal surface area (10). Short bowel syndrome (SBS) is a major cause of IF and generally occurs with loss of ϳ50 -75% of small intestinal length (33). Congenital anomalies and perinatal disorders of the small intestine, such as gastroschisis, intestinal atresia, malrotation with volvulus, and necrotizing enterocolitis, may lead to SBS in children (32), whereas trauma and intestinal ischemia from fixation within an internal hernia following gastric bypass surgery are leading causes of SBS in adults. A 2004 study found an incidence of 22.1/1,000 neonatal intensive care unit admissions and a population estimate of 24.5/100,000 live births (35). The incidence of SBS is increasing, and morbidity and cost remain high, with a 30% 5-yr ...

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mentioning

confidence: 99%

Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function

Grant

Mojica

Sala

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Initial experiments showed production of tissue-engineered small intestine with cytodifferentiation and phenotypic maturation as well as apical staining of brush-border enzymes and basolateral staining for laminin. An Ussing chamber study also indicated similar transepithelial resistance between native intestine and the tissue-engineered construct (Choi et al 1998). On histology, tissue-engineered small intestine has a polarized epithelium with appropriate reconstitution of the other layers of the intestinal wall, and there is substantial vascularization accompanying the growth (Choi et al 1998).…”

Section: Tissue Engineering the Small Intestinementioning

confidence: 82%

“…An Ussing chamber study also indicated similar transepithelial resistance between native intestine and the tissue-engineered construct (Choi et al 1998). On histology, tissue-engineered small intestine has a polarized epithelium with appropriate reconstitution of the other layers of the intestinal wall, and there is substantial vascularization accompanying the growth (Choi et al 1998). Addition of endothelial cells or specific trophic factors does not seem to Intestinal failure 741 be necessary.…”

Section: Tissue Engineering the Small Intestinementioning

confidence: 85%

“…A refinement of these techniques in the past 2 years has led to the generation of better tissue-engineered small intestine and the novel formation of tissue-engineered oesophagus, colon, spleen (Grikscheit et al 2001(Grikscheit et al , 2003a and stomach (Grikscheit & Vacanti, 2003). The generation of a composite tissue resembling small intestine generated from intestinal crypt cells paratopically transplanted as epithelial organoid units was first reported by the Boston group in 1998 (Choi et al 1998). Organoid units are obtained from full-thickness harvests of small intestine.…”

Section: Tissue Engineering the Small Intestinementioning

confidence: 99%

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Tissue engineering of the gastrointestinal tract for surgical replacement: a nutrition tool of the future?

Grikscheit

2003

Proc. Nutr. Soc.

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Optimal nutrition depends on the multiple complex functions performed by the gastrointestinal tract, which range from basic functions such as storage, conduit and mechanical processing to more finely regulated capabilities such as vectorial transport, immune defence and cell signalling. Surgical strategies to supply lacking gastrointestinal tract tissues have relied on either replacement by proxy (surgical substitution) or the introduction of prostheses. Tissue engineering seeks to replace missing tissues with engineered tissues that more accurately reproduce the native physiological and anatomical milieu. It is now possible to engineer several areas of the gastrointestinal tract with high fidelity, and to employ tissue-engineered bowel in replacement in animal models. These replacement models have reflected excellent anatomical and physiological recapitulation of native bowel by the tissue-engineered constructsin vivo.

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“…TESI contained crypts and villi similar to native intestine. The brush border was positive for the enzyme sucrase and evidence for ion transport activity was present although reduced compared with native intestine (Choi et al 1998). The intestinal immune tissue in TESI more closely resembled that of native jejunum when matured in continuity with native intestine thus showing ability to respond to luminal factors (Perez et al 2002).…”

Section: Small Intestinementioning

confidence: 96%

Tissue Engineering Functional Gastrointestinal Regions: The Importance of Stem and Progenitor Cells

Trecartin

Grikscheit

2017

Cold Spring Harb Perspect Med

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Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine

Cited by 99 publications

References 12 publications

Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function

Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function

Tissue engineering of the gastrointestinal tract for surgical replacement: a nutrition tool of the future?

Tissue Engineering Functional Gastrointestinal Regions: The Importance of Stem and Progenitor Cells

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