Gradients in the in vivo intestinal stem cell compartment and their in vitro recapitulation in mimetic platforms

Malijauskaite, Sigita; Connolly, Sinéad; Newport, David; McGourty, Kieran

doi:10.1016/j.cytogfr.2021.03.002

Cited by 15 publications

(17 citation statements)

References 128 publications

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“…In the case of RPE1 cells used in this study, the use of these hydrogels has the potential to model glaucoma or other degenerative disorders affecting the ocular system components or even beyond that to model gastrointestinal system tissues, such as intestinal mucosal epithelium, where cells essentially grow in 2D along the crypt villus unit. 3 The hydrogels formed had excellent swelling properties, exceeding 100% in each case, and were found to be highly biocompatible during evaluation with RPE1 cell lines. Significantly, the modified PAA-Cys hydrogels supported cell adhesion without the need for surface modification, and their mechanical properties were seen to directly influence cell proliferation.…”

Section: ■ Conclusionmentioning

confidence: 99%

“…These macromolecules provide not only structural support for cell attachment but also external cues to drive cell differentiation, migration, and growth. 1 − 3 In addition to insoluble ECM factors, cells are in constant contact with tissue-specific soluble growth factor gradients, which are also involved in cell survival, proliferation, and terminal differentiation. 3 − 6 …”

Section: Introductionmentioning

confidence: 99%

“… 1 − 3 In addition to insoluble ECM factors, cells are in constant contact with tissue-specific soluble growth factor gradients, which are also involved in cell survival, proliferation, and terminal differentiation. 3 − 6 …”

Section: Introductionmentioning

confidence: 99%

“…Cells in in vivo systems exist in a complex three-dimensional (3D) network of an extracellular matrix (ECM) composed of insoluble macromolecules such as collagens, fibronectin, elastin, and laminins. These macromolecules provide not only structural support for cell attachment but also external cues to drive cell differentiation, migration, and growth. − In addition to insoluble ECM factors, cells are in constant contact with tissue-specific soluble growth factor gradients, which are also involved in cell survival, proliferation, and terminal differentiation. − …”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Poly(acrylic acid)-Cysteine-Based Hydrogels with Highly Customizable Mechanical Properties for Advanced Cell Culture Applications

et al. 2022

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The fabrication of highly customizable scaffolds is a key enabling technology in the development of predictive in vitro cell models for applications in drug discovery, cancer research, and regenerative medicine. Naturally derived and synthetic hydrogels are good candidates for in vitro cell growth studies, owing to their soft and biocompatible nature; however, they are often hindered by limited ranges of stiffness and the requirement to modify the gel with additional extracellular matrix (ECM) proteins for cell adherence. Here, we report on the synthesis of a printable synthetic hydrogel based on cysteine-modified poly(acrylic acid) (PAA-Cys) with tuneable mechanical and swelling properties by incorporating acrylic acid into the PAA-Cys network and subsequent photoinitiated thiol-acrylate cross-linking. Control of the acrylic acid concentration and UV curing time produces a series of hydrogels with swelling ratios in excess of 100% and Young’s modulus values ranging from ∼2 to ∼35 kPa, of which most soft tissues fall within. Biocompatibility studies with RPE1 cells showed excellent cell adhesion and cell viability without the need for further modification with ECM proteins, but still can be modified as needed. The versatility of the hydrogel tuneable properties is demonstrated by culturing with RPE1 cells, which in vivo perform an important function in the visual process and the dysfunction of which may lead to various retinal abnormalities, such as glaucoma.

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Section: ■ Conclusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of Poly(acrylic acid)-Cysteine-Based Hydrogels with Highly Customizable Mechanical Properties for Advanced Cell Culture Applications

et al. 2022

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“…However, intestinal microbiota should not be ignored as ISC and crypt-villus/crypt regulators during homeostasis and disease, some activity of which may be via novel as yet unknown mechanisms [ 99 ]. The O 2 gradient along the crypt-villus/crypt axis also regulates anaerobic microbiome composition and cellular activity [ 100 ]. O 2 availability may therefore also help to regulate the ISC niche.…”

Section: Key Intestinal Stem Cell Niche Componentsmentioning

confidence: 99%

Identifying key regulators of the intestinal stem cell niche

Duckworth

2021

Biochemical Society Transactions

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The intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the maintenance of intestinal homeostasis and are derived from adult intestinal stem cells (ISCs). Actively cycling ISCs divide by a neutral drift mechanism yielding either ISCs or transit-amplifying epithelial cells, the latter of which differentiate to become either absorptive lineages or to produce secretory factors that contribute further to intestinal barrier maintenance or signal to other cellular compartments. The mechanisms controlling ISC abundance, longevity and activity are regulated by several different cell populations and signalling pathways in the intestinal lamina propria which together form the ISC niche. However, the complexity of the ISC niche and communication mechanisms between its different components are only now starting to be unravelled with the assistance of intestinal organoid/enteroid/colonoid and single-cell imaging and sequencing technologies. This review explores the interaction between well-established and emerging ISC niche components, their impact on the intestinal epithelium in health and in the context of intestinal injury and highlights future directions and implications for this rapidly developing field.

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An iPSC-derived small intestine-on-chip with self-organizing epithelial, mesenchymal, and neural cells

Moerkens,

Mooiweer,

Ramírez-Sánchez

et al. 2024

Cell Reports

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Gradients in the in vivo intestinal stem cell compartment and their in vitro recapitulation in mimetic platforms

Cited by 15 publications

References 128 publications

Synthesis of Poly(acrylic acid)-Cysteine-Based Hydrogels with Highly Customizable Mechanical Properties for Advanced Cell Culture Applications

Synthesis of Poly(acrylic acid)-Cysteine-Based Hydrogels with Highly Customizable Mechanical Properties for Advanced Cell Culture Applications

Identifying key regulators of the intestinal stem cell niche

An iPSC-derived small intestine-on-chip with self-organizing epithelial, mesenchymal, and neural cells

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