Intestinal Organoids&amp;mdash;Current and Future Applications

Meneses, André Marcelo Conceição; Schneeberger, Kerstin; Kruitwagen, Hedwig S.; Penning, Louis C.; Steenbeek, Frank G. van; Burgener, Iwan; Spee, Bart

doi:10.20944/preprints201608.0090.v1

2016

DOI: 10.20944/preprints201608.0090.v1

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Intestinal Organoids—Current and Future Applications

André Marcelo Conceição Meneses¹,

Kerstin Schneeberger²,

Hedwig S. Kruitwagen³

et al.

Abstract: Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology … Show more

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Cited by 3 publications

References 39 publications

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Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Sahoo

Martinez

Dao

et al. 2023

Cells

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A key component of efforts to identify the biological and drug-specific aspects contributing to therapeutic failure or unexpected exposure-associated toxicity is the study of drug–intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, relatively little information is available for similar evaluations in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug–gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in developing such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine-colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this canine-colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both the absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine-colonoid-derived monolayers and compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.

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Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Sahoo

Martinez

Dao

et al. 2023

Cells

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A Critical Review on In Vitro and Ex Vivo Models of the Intestinal Epithelium of Humans and Monogastric Animals

Costa,

de Carvalho,

de Oliveira

et al. 2024

Gastrointestinal Disorders

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Recently, the bioactive potential of several functional ingredients and biomolecules has been evaluated regarding human and animal nutrition. The digestive process from food intake to absorption and metabolism are important events that induce changes in ingredients, which affect their bioactivity. Consequently, there is a need to assess the bioavailability and bioaccessibility of these compounds. The methodology for the simulation of the human gastrointestinal tract has been standardized (INFOGEST protocol), while a gastrointestinal protocol for other animals (e.g., ruminants or broilers) has yet to be established. However, INFOGEST allows us only to predict bioaccessibility, leaving a gap regarding a methodology able to assess bioavailability by mimicking intestinal permeability and absorption. Several approaches—including in vitro, ex vivo, in situ and in vivo methods—can be found in the literature, aiming to tackle transepithelial routes, but leading to different results concerning the bioefficiency of the compounds studied. Therefore, this review aims to assess the current state-of-the-art regarding monogastric intestinal dynamics, absorption, and permeability events. Moreover, it compiled methodologies for simulating intestinal absorption in several biological systems, while reasoning their advantages, disadvantages, applications in ingredient development and the existing gaps.

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The Effect of Complex Alleles of the CFTR Gene on the Clinical Manifestations of Cystic Fibrosis and the Effectiveness of Targeted Therapy

Krasnova,

Efremova,

Bukhonin

et al. 2023

IJMS

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The authors of this article analyzed the available literature with the results of studying the prevalence of complex alleles of the CFTR gene among patients with cystic fibrosis, and their pathogenicity and influence on targeted therapy with CFTR modulators. Cystic fibrosis (CF) is a multisystemic autosomal recessive disease caused by a defect in the expression of the CFTR protein, and more than 2000 genetic variants are known. Clinically significant variants are divided into seven classes. Information about the frequency of complex alleles appears in a number of registers, along with the traditional presentation of data on genetic variants. Complex alleles (those with the presence of more than two nucleotide variants on one allele) can complicate the diagnosis of the disease, and change the clinical manifestations of cystic fibrosis and the response to treatment, since each variant in the complex allele can contribute to the functional activity of the CFTR protein, changing it both in terms of increasing and decreasing function. The role of complex alleles is often underestimated, and their frequency has not been studied. At the moment, characteristic frequently encountered complex alleles have been found for several populations of patients with cystic fibrosis, but the prevalence and pathogenicity of newly detected complex alleles require additional research. In this review, more than 35 complex alleles of the CFTR gene from existing research studies were analyzed, and an analysis of their influence on the manifestations of the disease and the effectiveness of CFTR modulators was also described.

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Intestinal Organoids—Current and Future Applications

Cited by 3 publications

References 39 publications

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

A Critical Review on In Vitro and Ex Vivo Models of the Intestinal Epithelium of Humans and Monogastric Animals

The Effect of Complex Alleles of the CFTR Gene on the Clinical Manifestations of Cystic Fibrosis and the Effectiveness of Targeted Therapy

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