scholarly journals Biobanking of human gut organoids for translational research

Author(s):  
Francesca Perrone ◽  
Matthias Zilbauer

AbstractThe development of human organoid culture models has led to unprecedented opportunities to generate self-organizing, three-dimensional miniature organs that closely mimic in vivo conditions. The ability to expand, culture, and bank such organoids now provide researchers with the opportunity to generate next-generation living biobanks, which will substantially contribute to translational research in a wide range of areas, including drug discovery and testing, regenerative medicine as well as the development of a personalized treatment approach. However, compared to traditional tissue repositories, the generation of a living organoid biobank requires a much higher level of coordination, additional resources, and scientific expertise. In this short review, we discuss the opportunities and challenges associated with the generation of a living organoid biobank. Focusing on human intestinal organoids, we highlight some of the key aspects that need to be considered and provide an outlook for future development in this exciting field.

2001 ◽  
Vol 204 (21) ◽  
pp. 3621-3627 ◽  
Author(s):  
Anthony Herrel ◽  
Jay J. Meyers ◽  
Peter Aerts ◽  
Kiisa C. Nishikawa

SUMMARYChameleons capture prey items using a ballistic tongue projection mechanism that is unique among lizards. During prey capture, the tongue can be projected up to two full body lengths and may extend up to 600 % of its resting length. Being ambush predators, chameleons eat infrequently and take relatively large prey. The extreme tongue elongation (sixfold) and the need to be able to retract fairly heavy prey at any given distance from the mouth are likely to place constraints on the tongue retractor muscles. The data examined here show that in vivo retractor force production is almost constant for a wide range of projection distances. An examination of muscle physiology and of the ultrastructure of the tongue retractor muscle shows that this is the result (i) of active hyoid retraction, (ii) of large muscle filament overlap at maximal tongue extension and (iii) of the supercontractile properties of the tongue retractor muscles. We suggest that the chameleon tongue retractor muscles may have evolved supercontractile properties to enable a substantial force to be produced over a wide range of tongue projection distances. This enables chameleons successfully to retract even large prey from a variety of distances in their complex three-dimensional habitat.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ting-ye Wang ◽  
Jia-xu Chen

Curcumin is a compound extracted from the Curcuma longa L, which possesses a wide range of pharmacological effects. However, few studies have collected scientific evidence on its dual effect on angiogenesis. The present review gathered the fragmented information available in the literature to discuss the dual effect and possible mechanisms of curcumin on angiogenesis. Available information concerning the effect of curcumin on angiogenesis is compiled from scientific databases, including PubMed and Web of Science using the key term (curcumin and angiogenesis). The results were reviewed to identify relevant articles. Related literature demonstrated that curcumin has antiangiogenesis effect via regulating multiple factors, including proangiogenesis factor VEGF, MMPs, and FGF, both in vivo and in vitro, and could promote angiogenesis under certain circumstances via these factors. This paper provided a short review on bidirectional action of curcumin, which should be useful for further study and application of this compound that require further studies.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Shuji Toda ◽  
Shigehisa Aoki ◽  
Kazuyoshi Uchihashi ◽  
Aki Matsunobu ◽  
Mihoko Yamamoto ◽  
...  

The thyroid is composed of thyroid follicles supported by extracellular matrix, capillary network, and stromal cell types such as fibroblasts. The follicles consist of thyrocytes and C cells. In this microenvironment, thyrocytes are highly integrated in their specific structural and functional polarization, but monolayer and floating cultures cannot allow thyrocytes to organize the follicles with such polarity. In contrast, three-dimensional (3-D) collagen gel culture enables thyrocytes to form 3-D follicles with normal polarity. However, these systems never reconstruct the follicles consisting of both thyrocytes and C cells. Thyroid tissue-organotypic culture retains 3-D follicles with both thyrocytes and C cells. To create more appropriate experimental models, we here characterize four culture systems above and then introduce the models for studying thyroid biology and disorders. Finally, we propose a new approach to the cell type-specific culture systems on the basis of in vivo microenvironments of various cell types.


2018 ◽  
Author(s):  
Lawrance Chandra ◽  
Dana C Borcherding ◽  
Dawn Kingsbury ◽  
Todd Atherly ◽  
Yoko M Ambrosini ◽  
...  

AbstractBackgroundLarge animal models, such as the dog, are increasingly being used over rodent models for studying naturally occurring diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between currently used animal models (e.g. mouse) and humans, and expand the translational potential of the dog model, we developed a three dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.ResultsOrganoids were propagated from isolation of adult intestinal stem cells (ISC) from whole jejunal tissue as well as endoscopically obtained duodenal, ileal and colonic biopsy samples of healthy dogs and GI cases, including inflammatory bowel disease (IBD) and intestinal carcinomas. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization and transmission electron microscopy, and organoids mimicked the in vivo tissue environment. Physiological relevance of the enteroid system was defined using functional assays such as Optical Metabolic Imaging (OMI), the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research.ConclusionsIn summary, our findings establish the canine GI organoid systems as a novel model to study naturally occurring intestinal diseases in dogs and humans. Furthermore, canine organoid systems will help to elucidate host-pathogen interactions contributing to GI disease pathogenesis.


2020 ◽  
Vol 11 ◽  
pp. 204173142093340 ◽  
Author(s):  
Chengye Zhang ◽  
Zhaoting Yang ◽  
Da-Long Dong ◽  
Tae-Su Jang ◽  
Jonathan C. Knowles ◽  
...  

Cancer stem cells have been shown to be important in tumorigenesis processes, such as tumor growth, metastasis, and recurrence. As such, many three-dimensional models have been developed to establish an ex vivo microenvironment that cancer stem cells experience under in vivo conditions. Cancer stem cells propagating in three-dimensional culture systems show physiologically related signaling pathway profiles, gene expression, cell–matrix and cell–cell interactions, and drug resistance that reflect at least some of the tumor properties seen in vivo. Herein, we discussed the presently available Cancer stem cell three-dimensional culture models that use biomaterials and engineering tools and the biological implications of these models compared to the conventional ones.


2019 ◽  
Vol 5 (11) ◽  
pp. eaax4520 ◽  
Author(s):  
Yesl Jun ◽  
JaeSeo Lee ◽  
Seongkyun Choi ◽  
Ji Hun Yang ◽  
Maike Sander ◽  
...  

Native pancreatic islets interact with neighboring cells by establishing three-dimensional (3D) structures, and are surrounded by perfusion at an interstitial flow level. However, flow effects are generally ignored in islet culture models, although cell perfusion is known to improve the cell microenvironment and to mimic in vivo physiology better than static culture systems. Here, we have developed functional islet spheroids using a microfluidic chip that mimics interstitial flow conditions with reduced shear cell damage. Dynamic culture, compared to static culture, enhanced islet health and maintenance of islet endothelial cells, reconstituting the main component of islet extracellular matrix within spheroids. Optimized flow condition allowed localization of secreted soluble factors near spheroids, facilitating diffusion-mediated paracrine interactions within islets, and enabled long-term maintenance of islet morphology and function for a month. The proposed model can aid islet preconditioning before transplantation and has potential applications as an in vitro model for diabetic drug testing.


2007 ◽  
Vol 539-543 ◽  
pp. 511-516 ◽  
Author(s):  
Thomas J. Webster

Nanotechnology is being used to mimic structural components of our tissues in synthetic materials intended for various implant applications. Recent studies have highlighted that when compared to flat or micron rough surfaces, surfaces with nanofeatures promote optimal initial protein interactions necessary to mediate cell adhesion and subsequent tissue regrowth. This has been demonstrated for a wide range of implant chemistries (from ceramics to metals to polymers) and for a wide range of tissues (including bone, vascular, cartilage, bladder, and the central and peripheral nervous system). Importantly, these results have been seen at the in vitro and in vivo level. This short review paper will cover some of the more significant advancements in creating better implants through nanotechnology efforts.


2021 ◽  
Vol 22 (4) ◽  
pp. 2143 ◽  
Author(s):  
Justin J.Y. Tan ◽  
Duc-Viet Nguyen ◽  
John E. Common ◽  
Chunyong Wu ◽  
Paul C.L. Ho ◽  
...  

Hair follicle morphogenesis is heavily dependent on reciprocal, sequential, and epithelial-mesenchymal interaction (EMI) between epidermal stem cells and the specialized cells of the underlying mesenchyme, which aggregate to form the dermal condensate (DC) and will later become the dermal papilla (DP). Similar models were developed with a co-culture of keratinocytes and DP cells. Previous studies have demonstrated that co-culture with keratinocytes maintains the in vivo characteristics of the DP. However, it is often challenging to develop three-dimensional (3D) DP and keratinocyte co-culture models for long term in vitro studies, due to the poor intercellular adherence between keratinocytes. Keratinocytes exhibit exfoliative behavior, and the integrity of the DP and keratinocyte co-cultured spheroids cannot be maintained over prolonged culture. Short durations of culture are unable to sufficiently allow the differentiation and re-programming of the keratinocytes into hair follicular fate by the DP. In this study, we explored a microgel array approach fabricated with two different hydrogel systems. Using poly (ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA), we compare their effects on maintaining the integrity of the cultures and their expression of important genes responsible for hair follicle morphogenesis, namely Wnt10A, Wnt10B, and Shh, over prolonged duration. We discovered that low attachment surfaces such as PEGDA result in the exfoliation of keratinocytes and were not suitable for long-term culture. GelMA, on the hand, was able to sustain the integrity of co-cultures and showed higher expression of the morphogens overtime.


Author(s):  
Donghyun Kim ◽  
Yeo-Jun Yoon ◽  
Dojin Choi ◽  
Jisun Kim ◽  
Jae-Yol Lim

Lumen formation of salivary glands has been investigated using in vivo or ex vivo rudiment culture models. In this study, we used a three-dimensional (3D) salivary gland organoid culture system and demonstrated that lumen formation could be recapitulated in mouse SMG organoids. In our organoid culture system, lumen formation was induced by vasoactive intestinal peptide and accelerated by treatment with RA. Furthermore, lumen formation was observed in branching duct-like structure when cultured in combination of fibroblast growth factors (FGF) in the presence of retinoic acid (RA). We suggest RA signaling-mediated regulation of VIPR1 and KRT7 as the underlying mechanism for lumen formation, rather than apoptosis in the organoid culture system. Collectively, our results support a fundamental role for RA in lumen formation and demonstrate the feasibility of 3D organoid culture as a tool for studying salivary gland morphogenesis.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 289 ◽  
Author(s):  
Kathleen R. Markan

The term “FGF21 resistance” was first used to describe increased circulating FGF21 levels concomitant to decreased FGF21 receptor complex expression in white adipose tissue of obese mice.  Since this initial report, the term has been associated with a wide range of pathological states, including human obesity, in which circulating FGF21 levels are elevated. However, the notion of “FGF21 resistance” has been controversial partly due to difficulty in delineating the mechanisms underlying the physiological versus pharmacological effects of FGF21.  Here, key aspects of the term “FGF21 resistance” are discussed including; the origin and experimental context surrounding the term “FGF21 resistance”, new criteria for evaluating FGF21 sensitivity in vivo and finally, crucial unresolved questions regarding the function of FGF21 during obesity.


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