Probing the luminal microenvironment of reconstituted epithelial microtissues

Cerchiari, Alec E.; Samy, Karen E.; Todhunter, Michael E.; Schlesinger, Erica; Henise, Jeff; Rieken, Christopher; Gartner, Zev J.; Desai, Tejal A.

doi:10.1038/srep33148

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…quantify luminal osmolarity (see Glossary, Box 1) in vivo, although a recent study demonstrated the use of nano-osmometer in measuring interstitial fluid osmolarity in zebrafish explants (Krens et al, 2017). Polymeric sensors that measure the luminal pH will also reveal how tissues respond to the changing electrochemical environment in the lumen (Cerchiari et al, 2016). To further understand the roles of signalling, development of advanced proteomics to identify the molecules in lumina of small volume (∼10 nl) will be essential.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Integration of luminal pressure and signalling in tissue self-organization

Chan

Hiiragi

2020

Development

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Many developmental processes involve the emergence of intercellular fluid-filled lumina. This process of luminogenesis results in a build up of hydrostatic pressure and signalling molecules in the lumen. However, the potential roles of lumina in cellular functions, tissue morphogenesis and patterning have yet to be fully explored. In this Review, we discuss recent findings that describe how pressurized fluid expansion can provide both mechanical and biochemical cues to influence cell proliferation, migration and differentiation. We also review emerging techniques that allow for precise quantification of fluid pressure in vivo and in situ. Finally, we discuss the intricate interplay between luminogenesis, tissue mechanics and signalling, which provide a new dimension for understanding the principles governing tissue self-organization in embryonic development.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Integration of luminal pressure and signalling in tissue self-organization

Chan

Hiiragi

2020

Development

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“…To circumvent the challenge of microinjecting single Matrigel (BD Biosciences, San Diego, CA)-embedded organoids, a strategy based on the preferred adhesion of cells to ECM rather than nonadhesive microstructures was developed, enabling cell self-organization around a pH-sensing particle. 127 Refinements in strategies such as this may enable future delivery of analyte-sensing or drug-releasing microparticles and/or microbes to the lumen of organoids.…”

Section: Engineered In Vitro Gradientsmentioning

confidence: 99%

Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche

Wang

Kim

Hinman

et al. 2018

Cellular and Molecular Gastroenterology and Hepatology

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The relationship between intestinal stem cells (ISCs) and the surrounding niche environment is complex and dynamic. Key factors localized at the base of the crypt are necessary to promote ISC self-renewal and proliferation, to ultimately provide a constant stream of differentiated cells to maintain the epithelial barrier. These factors diminish as epithelial cells divide, migrate away from the crypt base, differentiate into the postmitotic lineages, and end their life span in approximately 7 days when they are sloughed into the intestinal lumen. To facilitate the rapid and complex physiology of ISC-driven epithelial renewal, in vivo gradients of growth factors, extracellular matrix, bacterial products, gases, and stiffness are formed along the crypt-villus axis. New bioengineered tools and platforms are available to recapitulate various gradients and support the stereotypical cellular responses associated with these gradients. Many of these technologies have been paired with primary small intestinal and colonic epithelial cells to re-create select aspects of normal physiology or disease states. These biomimetic platforms are becoming increasingly sophisticated with the rapid discovery of new niche factors and gradients. These advancements are contributing to the development of high-fidelity tissue constructs for basic science applications, drug screening, and personalized medicine applications. Here, we discuss the direct and indirect evidence for many of the important gradients found in vivo and their successful application to date in bioengineered in vitro models, including organ-on-chip and microfluidic culture devices.

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“…As a result, the single cells that were evenly distributed along the printed tube simultaneously aggregated to form multicellular spheroids and self-organized into lumenized cysts ( Figure 3G ). This transition—called lumenogenesis—is a hallmark of distinct epithelial morphogenesis that occurs under biomimetic conditions ( 120 ). In addition, the differentiation of Caco-2 cells into functional intestinal phenotypes was identified by the expression of EEC markers such as chromogranin A and lysozyme.…”

Section: Current In Vitro Gut Models With Differen...mentioning

confidence: 99%

Recent advances in biofabricated gut models to understand the gut-brain axis in neurological diseases

Han

Jang²

2022

Front. Med. Technol.

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Increasing evidence has accumulated that gut microbiome dysbiosis could be linked to neurological diseases, including both neurodegenerative and psychiatric diseases. With the high prevalence of neurological diseases, there is an urgent need to elucidate the underlying mechanisms between the microbiome, gut, and brain. However, the standardized aniikmal models for these studies have critical disadvantages for their translation into clinical application, such as limited physiological relevance due to interspecies differences and difficulty interpreting causality from complex systemic interactions. Therefore, alternative in vitro gut–brain axis models are highly required to understand their related pathophysiology and set novel therapeutic strategies. In this review, we outline state-of-the-art biofabrication technologies for modeling in vitro human intestines. Existing 3D gut models are categorized according to their topographical and anatomical similarities to the native gut. In addition, we deliberate future research directions to develop more functional in vitro intestinal models to study the gut–brain axis in neurological diseases rather than simply recreating the morphology.

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Probing the luminal microenvironment of reconstituted epithelial microtissues

Cited by 7 publications

References 28 publications

Integration of luminal pressure and signalling in tissue self-organization

Integration of luminal pressure and signalling in tissue self-organization

Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche

Recent advances in biofabricated gut models to understand the gut-brain axis in neurological diseases

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