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 Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.

1978 ◽  
Vol 147 (5) ◽  
pp. 1526-1531 ◽  
Author(s):  
D E Harrison ◽  
C M Astle ◽  
J A Delaittre
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Cell Types ◽  
Colony Growth ◽  
Normal Function ◽  
Stem Cell Lines ◽  
Marrow Stem Cell ◽  
Serial Transplantation

Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.

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.

Human Pluripotent Stem Cells and Drug Discovery: A New Beginning

2016 ◽  
Vol 1 (1) ◽  
pp. 27
Author(s):  
Vinod Verma ◽  
A. Mehta ◽  
S.J.S. Flora
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Pluripotent Stem Cells ◽  
Cost Effective ◽  
Cell Types ◽  
In Vitro Models ◽  
Human Pluripotent Stem Cells ◽  
Specific Cell ◽  
Attrition Rates

Human pluripotent stem cells (hPSCs) offer unique opportunities to discover and develop a new generation of drugs. Their ability to differentiate into virtually any cell type renders them a cost-effective, renewable source of tissue-specific cell types capable of predicting human responses towards novel chemical entities. Using these improved in vitro models based on physiologically relevant human cell types could result in identifying highly precise and safe compounds, thereby reducing drug attrition rates. Moreover, ability to develop humanised disease models for patient-stratified drug screening makes hPSCs an impeccable tool in translational medicine. In this mini-review we focus on the positives and negatives of utilising hPSC-derived cell types as drug discovery platforms with special emphasis on cardio-, hepato- and embryotoxicity.

scholarly journals Patentability of the Human Embryonic Stem Cell Lines: A Legal and Ethical Aspect

2020 ◽  
Author(s):  
Tansu Sayar Kanyış ◽  
Ezgi Arslan ◽  
Oğuzhan Kanyış
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Lines ◽  
Human Embryo ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Point Of View ◽  
Stem Cell Lines

In this study, patentability of the human embryonic stem cell lines has discussed in the legal and ethical perspectives. In vitro human embryonic stem cells can be defined as body parts that are departed from the body. Human embryonic stem cell lines are constituted of differentiated self-renewal pluripotent stem cells, which means they have no characteristics to become a human-being. However, interpreting the terms like human embryo and right to property widely can cause the human embryonic stem cell lines are misunderstood as unpatentable. For our point of view, giving the human embryo the protections of both personal rights of the donor and the right to property of the owner of the invention does not reduce the legal/moral status of the human embryo. Besides, the obligations which these rights imposes to their owners, such as the principle of human dignity and prohibition of financial gain can protect the human embryo in a better way.

scholarly journals Many Cells Make Life Work—Multicellularity in Stem Cell-Based Cardiac Disease Modelling

2018 ◽  
Vol 19 (11) ◽  
pp. 3361 ◽  
Author(s):  
Brian Wang ◽  
Worrapong Kit-Anan ◽  
Cesare Terracciano
Keyword(s):  
Heart Failure ◽  
Stem Cell ◽  
Cardiac Disease ◽  
Contractile Function ◽  
Sympathetic Neurons ◽  
Cell Types ◽  
Patient Specific ◽  
Disease Modelling ◽  
Great Opportunity

Cardiac disease causes 33% of deaths worldwide but our knowledge of disease progression is still very limited. In vitro models utilising and combining multiple, differentiated cell types have been used to recapitulate the range of myocardial microenvironments in an effort to delineate the mechanical, humoral, and electrical interactions that modulate the cardiac contractile function in health and the pathogenesis of human disease. However, due to limitations in isolating these cell types and changes in their structure and function in vitro, the field is now focused on the development and use of stem cell-derived cell types, most notably, human-induced pluripotent stem cell-derived CMs (hiPSC-CMs), in modelling the CM function in health and patient-specific diseases, allowing us to build on the findings from studies using animal and adult human CMs. It is becoming increasingly appreciated that communications between cardiomyocytes (CMs), the contractile cell of the heart, and the non-myocyte components of the heart not only regulate cardiac development and maintenance of health and adult CM functions, including the contractile state, but they also regulate remodelling in diseases, which may cause the chronic impairment of the contractile function of the myocardium, ultimately leading to heart failure. Within the myocardium, each CM is surrounded by an intricate network of cell types including endothelial cells, fibroblasts, vascular smooth muscle cells, sympathetic neurons, and resident macrophages, and the extracellular matrix (ECM), forming complex interactions, and models utilizing hiPSC-derived cell types offer a great opportunity to investigate these interactions further. In this review, we outline the historical and current state of disease modelling, focusing on the major milestones in the development of stem cell-derived cell types, and how this technology has contributed to our knowledge about the interactions between CMs and key non-myocyte components of the heart in health and disease, in particular, heart failure. Understanding where we stand in the field will be critical for stem cell-based applications, including the modelling of diseases that have complex multicellular dysfunctions.

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.

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.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

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