Comparison of Different <i>In Vivo</i> Incubation Sites to Produce Tissue-Engineered Small Intestine

Cromeens, Barrett P.; Wang, Yijie; Fisher, K; Johnson, Jed; Chakroff, Jason; Besner, Gail E.

doi:10.1089/ten.tea.2017.0313

Cited by 8 publications

(13 citation statements)

References 34 publications

(36 reference statements)

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“…3 The incubation sites include omentum, [10][11][12] kidney capsule, [13][14][15] or anterior abdominal wall. 16 Our previous results demonstrate improved TESI structure with implantation into the omentum. 16 ISCs, located in the crypts at the bottom of the intestinal mucosa, are obtained from the digestion of donor's intestine, purified, and concentrated for seeding onto scaffolds.…”

Section: Introductionmentioning

confidence: 85%

“…16 Our previous results demonstrate improved TESI structure with implantation into the omentum. 16 ISCs, located in the crypts at the bottom of the intestinal mucosa, are obtained from the digestion of donor's intestine, purified, and concentrated for seeding onto scaffolds. 17 Based on marker expression, cycling kinetics and basal location, mouse small intestinal crypts appear to harbor at least two distinct populations of stem cells.…”

Section: Introductionmentioning

confidence: 85%

“…After macroscopic evaluation, the volume of the explants was measured using the water displacement method as we have previously described. 16 Explants were then fixed in 10% neutral buffered formalin for histological assessment.…”

Section: Implantation and In Vivo Incubation Of Cell-seeded Scaffoldsmentioning

confidence: 99%

“…Circumferential neomucosal length, which represents the quantity of TESI produced, was measured by tracking the neomucosa along the circumference of the lumen using ImageJ software as we have previously described. 16 Villus height and crypt depth, representing the quality of TESI produced, was measured by two observers from the top to the bottom of the villi and crypts using ImageJ software as described previously. 16 A mean of 5 villi per crypts per section in 2 sections from each of the neomucosa positive specimens was analyzed (n = 120 for fetal and newborn donors, n = 100 for weanling donors, and n = 80 for adult donors).…”

Section: Morphological Assessment Of Tesimentioning

confidence: 99%

“…16 Villus height and crypt depth, representing the quality of TESI produced, was measured by two observers from the top to the bottom of the villi and crypts using ImageJ software as described previously. 16 A mean of 5 villi per crypts per section in 2 sections from each of the neomucosa positive specimens was analyzed (n = 120 for fetal and newborn donors, n = 100 for weanling donors, and n = 80 for adult donors). Sections were also subjected to immunofluorescence (IF) staining to identify the following: Ki67 staining to identify proliferating cells, chromogranin A staining to detect enteroendocrine cells, lysozyme staining to detect Paneth cells, villin staining to detect enterocytes, and desmin staining to detect smooth muscle cells.…”

Section: Morphological Assessment Of Tesimentioning

confidence: 99%

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Production of Tissue-Engineered Small Intestine in Rats with Different Ages of Cell Donors

Wang

Chakroff

Johnson

et al. 2019

Tissue Engineering Part A

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Objective: The objective of this study was to compare the impact of different ages of cell donors on the production of tissue-engineered small intestine (TESI). Materials and Methods: Four different ages of Lewis rats were chosen as donors of intestinal organoids: E18 fetuses, 5-day-old newborns, 21-day-old weanlings, and 6-week-old adults. The harvested intestine was exposed to enzymatic digestion to release intestinal stem cell (ISC)-containing organoids. Organoids were purified, concentrated, and seeded onto tubular polyglycolic acid scaffolds. Seeded scaffolds were attached to the anterior surface of the abdominal wall in recipient nude rats. After 4 weeks of in vivo incubation, specimens from each donor age were explanted for evaluation. Results: TESI produced from E18 fetal organoids demonstrated the largest quantity of neomucosa as confirmed by gross observation and volume measurement, and intermediate quality of the neomucosa as determined by periodic acid-Schiff staining. TESI produced from newborn organoids was of intermediate quantity, but had the best quality of neomucosa. TESI produced from weanling organoids had lower quantity and poorer quality neomocosa, with TESI produced from adult organoids having the worst results. Immunofluorescence staining confirmed the presence of all epithelial cell lineages in TESI produced from all donor ages, with the highest density of proliferating Ki67-positive cells seen in TESI produced from the youngest cell donors. Gene expression for Lgr5 (indicative of actively dividing ISCs) and for Bmi1 and Hopx (indicative of quiescent stem cells) was higher in younger donor intestines. Conclusions: Among the four ages of cell donors, using 5-day-old newborn rats as cell donors produced the best quality of TESI, with a single patent lumen. TESI produced from other cell donors revealed multiple neomucosal cysts mixed with varying degrees of fibrous tissue, which may be not appropriate for future clinical application.This study compared side-by-side the impact of donor age on the production of tissue-engineered small intestine (TESI). Each age represents a specific period of life: E18 for fetuses, 5-day-old pups for neonates, 21-day-old rats for weanlings, and 6week-old rats for adults. The TESI produced was compared macroscopically and microscopically. The mechanism(s) contributing to the differences observed was explored by detecting proliferating cells in the TESI and by analyzing intestinal stem cell gene expression in donor cells. These data may provide valuable information for future application of TESI clinically.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 85%

Section: Implantation and In Vivo Incubation Of Cell-seeded Scaffoldsmentioning

confidence: 99%

Section: Morphological Assessment Of Tesimentioning

confidence: 99%

Section: Morphological Assessment Of Tesimentioning

confidence: 99%

See 3 more Smart Citations

Production of Tissue-Engineered Small Intestine in Rats with Different Ages of Cell Donors

Wang

Chakroff

Johnson

et al. 2019

Tissue Engineering Part A

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Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip

Chen

Zhao

et al. 2021

Stem Cell Rev and Rep

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Intestinal dysfunction is frequently driven by abnormalities of specific genes, microbiota, or microenvironmental factors, which usually differ across individuals, as do intestinal physiology and pathology. Therefore, it’s necessary to develop personalized therapeutic strategies, which are currently limited by the lack of a simulated intestine model. The mature human intestinal mucosa is covered by a single layer of columnar epithelial cells that are derived from intestinal stem cells (ISCs). The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments. However, a simulated intestine model will serve as an indispensable foundation for personalized drug screening. In this article, we review the advantages and disadvantages of conventional 2-dimensional models, intestinal organoid models, and current microfluidic intestine-on-a-chip (IOAC) models. The main technological strategies are summarized, and an advanced microfluidic primary IOAC model is proposed for personalized intestinal medicine. In this model, primary ISCs and the microbiome are isolated from individuals and co-cultured in a multi-channel microfluidic chip to establish a microengineered intestine device. The device can faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions. Moreover, the ISCs can be genetically edited before seeding, and monitoring sensors and post-analysis abilities can also be incorporated into the device to achieve high-throughput and rapid pharmaceutical studies. We also discuss the potential future applications and challenges of the microfluidic platform. The development of cell biology, biomaterials, and tissue engineering will drive the advancement of the simulated intestine, making a significant contribution to personalized medicine in the future. Graphical abstract The intestine is a primary organ for digestion, absorption, and metabolism, as well as a major site for the host-commensal microbiota interaction and mucosal immunity. The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments, though physiological 3-dimensional of the native small intestinal epithelial tissue has been well documented. An intestinal stem cells-based microfluidic intestine-on-a-chip model that faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions will make a significant contribution.

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Generating an Artificial Intestine for the Treatment of Short Bowel Syndrome

Kovler

Hackam

2019

Gastroenterology Clinics of North America

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Comparison of Different In Vivo Incubation Sites to Produce Tissue-Engineered Small Intestine

Cited by 8 publications

References 34 publications

Production of Tissue-Engineered Small Intestine in Rats with Different Ages of Cell Donors

Production of Tissue-Engineered Small Intestine in Rats with Different Ages of Cell Donors

Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip

Generating an Artificial Intestine for the Treatment of Short Bowel Syndrome

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