scholarly journals Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction

2021 ◽  
Vol 12 ◽  
Author(s):  
Fatina Siwczak ◽  
Elise Loffet ◽  
Mathilda Kaminska ◽  
Hristina Koceva ◽  
Maxime M. Mahe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Intestinal Epithelium ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Intestinal Microbiome ◽  
Intestinal Stem Cell ◽  
Specific Cell ◽  
Chip Technology ◽  
On Chip

The gut is a tubular organ responsible for nutrient absorption and harbors our intestinal microbiome. This organ is composed of a multitude of specialized cell types arranged in complex barrier-forming crypts and villi covered by a mucosal layer controlling nutrient passage and protecting from invading pathogens. The development and self-renewal of the intestinal epithelium are guided by niche signals controlling the differentiation of specific cell types along the crypt-villus axis in the epithelium. The emergence of microphysiological systems, or organ-on-chips, has paved the way to study the intestinal epithelium within a dynamic and controlled environment. In this review, we describe the use of organ-on-chip technology to control and guide these differentiation processes in vitro. We further discuss current applications and forthcoming strategies to investigate the mechanical processes of intestinal stem cell differentiation, tissue formation, and the interaction of the intestine with the microbiota in the context of gastrointestinal diseases.

Biomaterials Nano Geometry for Control of Stem Cell Differentiation

2009 ◽  
Vol 1239 ◽  
Author(s):  
Karla Brammer ◽  
Seunghan Oh ◽  
Sungho Jin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Differentiation ◽  
Human Mesenchymal Stem Cell ◽  
Oxide Surface ◽  
Specific Cell ◽  
Implant Surface ◽  
Multipotent Stem Cells

AbstractTwo important goals in stem cell research are to control the cell proliferation without differentiation, and also to direct the differentiation into a specific cell lineage when desired. Recent studies indicate that the nanostructures substantially influence the stem cell behavior. It is well known that mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into stromal lineages such as adipocyte, chondrocyte, fibroblast, myocyte, and osteoblast cell types. By examining the cellular behavior of MSCs cultured in vitro on nanostructures, some understanding of the effects that the nanostructures have on the stem cell’s response has been obtained. Here we demonstrate that TiO2 nanotubes produced by anodization on Ti implant surface can regulate human mesenchymal stem cell (hMSC) differentiation towards an osteoblast lineage in the absence of osteogenic inducing factors. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion at smaller diameter levels or a specific differentiation of hMSCs into osteoblasts using only the geometric cues. Small (˜30 nm diameter) nanotubes promoted adhesion without noticeable differentiation, while larger (˜70 - 100 nm diameter) nanotubes elicited a dramatic, ˜10 fold stem cell elongation, which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for novel orthopaedics-related hMSC treatments. The fact that a guided and preferential osteogenic differentiation of stem cells can be achieved using substrate nanotopography alone without using potentially toxic, differentiation-inducing chemical agents is significant, which can be useful for future development of novel and enhanced stem cell control and therapeutic implant development.

scholarly journals Glycosaminoglycans as regulators of stem cell differentiation

2011 ◽  
Vol 39 (1) ◽  
pp. 383-387 ◽  
Author(s):  
Raymond A.A. Smith ◽  
Kate Meade ◽  
Claire E. Pickford ◽  
Rebecca J. Holley ◽  
Catherine L.R. Merry
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Es Cells ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Specific Pattern ◽  
Embryonic Stem Cell Differentiation ◽  
Specific Cell

ES (embryonic stem) cell differentiation is dependent on the presence of HS (heparan sulfate). We have demonstrated that, during differentiation, the evolution of specific cell lineages is associated with particular patterns of GAG (glycosaminoglycan) expression. For example, different HS epitopes are synthesized during neural or mesodermal lineage formation. Cell lines mutant for various components of the HS biosynthetic pathway are selectively impaired in their differentiation, with lineage-specific effects observed for some lines. We have also observed that the addition of soluble GAG saccharides to cells, with or without cell-surface HS, can influence the pace and outcome of differentiation, again highlighting specific pattern requirements for particular lineages. We are combining this work with ongoing studies into the design of artificial cell environments where we have optimized three-dimensional scaffolds, generated by electrospinning or by the formation of hydrogels, for the culture of ES cells. By permeating these scaffolds with defined GAG oligosaccharides, we intend to control the mechanical environment of the cells (via the scaffold architecture) as well as their biological signalling environment (using the oligosaccharides). We predict that this will allow us to control ES cell pluripotency and differentiation in a three-dimensional setting, allowing the generation of differentiated cell types for use in drug discovery/testing or in therapeutics.

scholarly journals Human Embryo Models and Drug Discovery

2021 ◽  
Vol 22 (2) ◽  
pp. 637
Author(s):  
Margit Rosner ◽  
Manuel Reithofer ◽  
Dieter Fink ◽  
Markus Hengstschläger
Keyword(s):  
Stem Cell ◽  
Drug Discovery ◽  
Cell Lines ◽  
Human Embryo ◽  
Cell Types ◽  
Human Cells ◽  
Disease Modelling ◽  
Specific Cell ◽  
Transformed Cell Lines

For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of human maladies with the aim to develop innovative and effective therapeutic strategies. Since many years, animal models and highly proliferative transformed cell lines are successfully used for disease modelling, drug discovery, target validation, and preclinical testing. Still, species-specific differences regarding genetics and physiology and the limited suitability of immortalized cell lines to draw conclusions on normal human cells or specific cell types, are undeniable shortcomings. The progress in human pluripotent stem cell research now allows the growth of a virtually limitless supply of normal and DNA-edited human cells, which can be differentiated into various specific cell types. However, cells in the human body never fulfill their functions in mono-lineage isolation and diseases always develop in complex multicellular ecosystems. The recent advances in stem cell-based 3D organoid technologies allow a more accurate in vitro recapitulation of human pathologies. Embryoids are a specific type of such multicellular structures that do not only mimic a single organ or tissue, but the entire human conceptus or at least relevant components of it. Here we briefly describe the currently existing in vitro human embryo models and discuss their putative future relevance for disease modelling and drug discovery.

scholarly journals Developing defined substrates for stem cell culture and differentiation

2018 ◽  
Vol 373 (1750) ◽  
pp. 20170230 ◽  
Author(s):  
Louise Hagbard ◽  
Katherine Cameron ◽  
Paul August ◽  
Christopher Penton ◽  
Malin Parmar ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Specific Cell ◽  
Biologically Relevant ◽  
Stem Cell Maintenance ◽  
Signalling Molecules ◽  
Cell Matrix

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro , but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell–matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

scholarly journals Automated optimization of endoderm differentiation on chip

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Jessi Carolina Ardila Riveros ◽  
Anna Karolina Blöchinger ◽  
Scott Atwell ◽  
Michel Moussus ◽  
Nina Compera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Cultures ◽  
Cell Types ◽  
Cell Replacement ◽  
Endoderm Differentiation ◽  
On Chip ◽  
Automated Optimization

Here we developed an automated mLSI chip platform with general analytical workflow for 3D stem cell cultures offers the optimization of in vitro generation of various cell types for cell replacement therapies.

scholarly journals Ceramide in Stem Cell Differentiation and Embryo Development: Novel Functions of a Topological Cell-Signaling Lipid and the Concept of Ceramide Compartments

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Erhard Bieberich
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Signaling ◽  
Embryo Development ◽  
Knockout Mice ◽  
Lipid A ◽  
Developmental Stages ◽  
Stem Cell Differentiation ◽  
Cell Types

In the last two decades, the view on the function of ceramide as a sole metabolic precursor for other sphingolipids has completely changed. A plethora of studies has shown that ceramide is an important lipid cell-signaling factor regulating apoptosis in a variety of cell types. With the advent of new stem cell technologies and knockout mice for specific steps in ceramide biosynthesis, this view is about to change again. Recent studies suggest that ceramide is a critical cell-signaling factor for stem cell differentiation and cell polarity, two processes at the core of embryo development. This paper discusses studies on ceramide usingin vitrodifferentiated stem cells, embryo cultures, and knockout mice with the goal of linking specific developmental stages to exciting and novel functions of this lipid. Particular attention is devoted to the concept of ceramide as a topological cell-signaling lipid: a lipid that forms distinct structures (membrane domains and vesicles termed “sphingosome”), which confines ceramide-induced cell signaling pathways to localized and even polarized compartments.

scholarly journals Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1000
Author(s):  
Nathalie Sphyris ◽  
Michael C. Hodder ◽  
Owen J. Sansom
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Intestinal Epithelium ◽  
Immune Surveillance ◽  
Cell Types ◽  
Therapy Resistance ◽  
Intestinal Stem Cell ◽  
Signalling Pathways ◽  
Post Injury ◽  
Pleiotropic Functions

The intestinal epithelium fulfils pleiotropic functions in nutrient uptake, waste elimination, and immune surveillance while also forming a barrier against luminal toxins and gut-resident microbiota. Incessantly barraged by extraneous stresses, the intestine must continuously replenish its epithelial lining and regenerate the full gamut of specialized cell types that underpin its functions. Homeostatic remodelling is orchestrated by the intestinal stem cell (ISC) niche: a convergence of epithelial- and stromal-derived cues, which maintains ISCs in a multipotent state. Following demise of homeostatic ISCs post injury, plasticity is pervasive among multiple populations of reserve stem-like cells, lineage-committed progenitors, and/or fully differentiated cell types, all of which can contribute to regeneration and repair. Failure to restore the epithelial barrier risks seepage of toxic luminal contents, resulting in inflammation and likely predisposing to tumour formation. Here, we explore how homeostatic niche-signalling pathways are subverted in tumorigenesis, enabling ISCs to gain autonomy from niche restraints (“ISC emancipation”) and transform into cancer stem cells capable of driving tumour initiation, progression, and therapy resistance. We further consider the implications of the pervasive plasticity of the intestinal epithelium for the trajectory of colorectal cancer, the emergence of distinct molecular subtypes, the propensity to metastasize, and the development of effective therapeutic strategies.

scholarly journals Junctional Adhesion Molecule 3 Expression in the Mouse Airway Epithelium Is Linked to Multiciliated Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Clara Maria Mateos-Quiros ◽  
Sergio Garrido-Jimenez ◽  
Guadalupe Álvarez-Hernán ◽  
Selene Diaz-Chamorro ◽  
Juan Francisco Barrera-Lopez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adhesion Molecule ◽  
Airway Epithelium ◽  
Barrier Function ◽  
Cell Types ◽  
Specific Cell ◽  
Recycling Endosome ◽  
Multiciliated Cells ◽  
Beating Frequency

Tight-junction (TJ) proteins are essential for establishing the barrier function between neighbor epithelial cells, but also for recognition of pathogens or cell migration. Establishing the expression pattern and localization of different TJ proteins will help to understand the development and physiology of the airway. Here we identify that the junctional adhesion molecule 3 (Jam3) expression is restricted to multiciliated cells (MCCs) in the airway epithelium. In vitro, Jam3 expression varies along airway basal stem cell (BSC) differentiation and upon DAPT treatment or IL6 exposure. However, Jam3 is not required for BSC differentiation to specific cell types. In addition, we found that MCC lacking Jam3 display normal cilia morphology and cilia beating frequency with a delay in BB assembly/positioning in MCCs during differentiation. Remarkably, Jam3 in MCC is mostly localized to subapical organelles, which are negative for the apical recycling endosome marker Rab11 and positive for EEA1. Our data show that Jam3 expression is connected to mature MCC in the airway epithelium and suggest a Jam3 role unrelated to its known barrier function.

scholarly journals Autologous human immunocompetent white adipose tissue-on-chip

2021 ◽  
Author(s):  
Julia Rogal ◽  
Raylin Xu ◽  
Julia Roosz ◽  
Claudia Teufel ◽  
Madalena Cipriano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Associated Diseases ◽  
Chip Technology ◽  
Vitro Model ◽  
On Chip

Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of 'diabesity' and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity to fit a specific purpose via a flexible mix-and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human- based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.

scholarly journals Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Alejandro Luarte ◽  
Luis Federico Bátiz ◽  
Ursula Wyneken ◽  
Carlos Lafourcade
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neurodegenerative Disorders ◽  
Cell Types ◽  
Therapeutic Benefit ◽  
Brain Diseases ◽  
Specific Cell ◽  
Novel Approaches

Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been testedin vivoandin vitroas therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

Sign in / Sign up

Export Citation Format

Share Document