scholarly journals Modeling Host-Virus Interactions in Viral Infectious Diseases Using Stem-Cell-Derived Systems and CRISPR/Cas9 Technology

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 124 ◽  
Author(s):  
Jihoon Kim ◽  
Bon-Kyoung Koo ◽  
Ki-Jun Yoon
Keyword(s):  
Stem Cell ◽  
Viral Infections ◽  
Adult Stem Cell ◽  
Viral Pathogenesis ◽  
Extensive Study ◽  
Model Systems ◽  
Host Virus Interactions ◽  
Virus Interactions

Pathologies induced by viral infections have undergone extensive study, with traditional model systems such as two-dimensional (2D) cell cultures and in vivo mouse models contributing greatly to our understanding of host-virus interactions. However, the technical limitations inherent in these systems have constrained efforts to more fully understand such interactions, leading to a search for alternative in vitro systems that accurately recreate in vivo physiology in order to advance the study of viral pathogenesis. Over the last decade, there have been significant technological advances that have allowed researchers to more accurately model the host environment when modeling viral pathogenesis in vitro, including induced pluripotent stem cells (iPSCs), adult stem-cell-derived organoid culture systems and CRISPR/Cas9-mediated genome editing. Such technological breakthroughs have ushered in a new era in the field of viral pathogenesis, where previously challenging questions have begun to be tackled. These include genome-wide analysis of host-virus crosstalk, identification of host factors critical for viral pathogenesis, and the study of viral pathogens that previously lacked a suitable platform, e.g., noroviruses, rotaviruses, enteroviruses, adenoviruses, and Zika virus. In this review, we will discuss recent advances in the study of viral pathogenesis and host-virus crosstalk arising from the use of iPSC, organoid, and CRISPR/Cas9 technologies.

scholarly journals Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 914
Author(s):  
Melanie V. Brady ◽  
Flora M. Vaccarino
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Human Development ◽  
Disease Modeling ◽  
Model Systems ◽  
Advantages And Disadvantages ◽  
Technical Ability ◽  
Cellular Phenotypes

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.

scholarly journals Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Silvana Bardelli ◽  
Marco Moccetti
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Translational Medicine ◽  
Process Development ◽  
Therapeutic Potential ◽  
Adult Stem Cell ◽  
Cell Renewal ◽  
Stem Cell Niches

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regenerationin vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizingin vitroorin vivothe various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

scholarly journals STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM

1951 ◽  
Vol 94 (4) ◽  
pp. 269-289 ◽  
Author(s):  
Oscar C. Liu ◽  
Werner Henle
Keyword(s):  
Influenza Virus ◽  
Growth Curve ◽  
High Speed ◽  
Allantoic Fluid ◽  
In Vitro Tests ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Virus System

The role of inhibitors of hemagglutination in the evaluation of host-virus interactions in the chick embryo-influenza virus system has been analyzed. Comparisons were made between materials (allantoic fluids and membrane suspensions) derived from in vivo (growth curve) experiments at hourly intervals after inoculation, and from in vitro tests in which normal allantoic fluids and membrane suspensions were incubated with virus at 37°C. for various periods of time. In both instances large amounts of virus were added to the systems, resulting in comparable concentrations of the agent. The seeds employed were either fully active or irradiated by ultraviolet light to the extent that the virus lost its capacity to increase but kept its interfering and hemagglutinating properties. The various materials were assayed for (a) the hemagglutinating titers of the virus present in the systems before and after heating to 56°C.; (b) the concentration of inhibitor in the materials at various stages of incubation after heating to 70°C. for 30 minutes as measured by the hemagglutination-inhibition reaction with native or heated test virus (30 minutes 56°C.); and (c) the degree of adsorption of the hemagglutinins present in the materials onto chicken red cells at 0°C. and their subsequent elution at 37°C. The effects of receptor-destroying enzyme (RDE), treatment with sodium periodate, or high speed centrifugation on the inhibitory activities were studied in some of the tests. The essential results which indicate certain sources of error in the evaluation of host-virus interactions as well as means for studying virus activity at the early stages of the infectious process, were as follows: 1. Though some inhibitory effects on hemagglutination were noticeable in the allantoic fluid during the 1st hour after inoculation they were, as a rule, no longer apparent after this interval, and treatment with RDE did not increase the hemagglutinin titers. Thus, the interpretation of growth curve data concerning allantoic fluids hardly seems to be affected by inhibitor. On the other hand, striking effects were noted with the membrane suspensions of growth curve experiments in that RDE shortened the latent period to 2 hours and the titers in the first few positive samples (4 to 5 hours) increased) whereas in later harvests no such effect was noted. Under these conditions complement-fixation antigens and hemagglutinins made their appearance in the tissues simultaneously and not as previously reported the former prior to the latter. However, the infectivity showed increments only several hours after these two activities had become measurable. Thus the hypothesis of the stagewise development of influenza virus is still supported by these data. 2. Using the inhibition of hemagglutination technic it was found that the inhibitor in allantoic fluid rapidly decreased as a result of the action of active and irradiated virus, but destruction was never complete. In the membranes of the in vivo series only active seed led to loss of inhibitor, again without complete destruction, beginning at the time complement-fixing antigen and hemagglutinins became measurable. Irradiated seed was without effect in vivo whereas, in the in vitro tests it equalled the activity of the active virus. The implications of this difference in the effectiveness of active and irradiated seed in vivo with regard to the understanding of the mode of viral multiplication are discussed. 3. Although many factors may influence the shape of adsorption-elution curves it is felt that at 0°C. the extent of adsorption is directly related to the amount of inhibitor present in the systems. In the early hours after inoculation the degree of adsorption was relatively small but it increased gradually with the time of incubation. The inhibitor of adsorption was destroyed by RDE and NaIO4 and was only partially sedimentable by high speed centrifugation. In every respect studied its properties corresponded with the findings obtained with inhibitors in the hemagglutination-inhibition technic. Although the difference in the rapidity of inhibitor destruction as measured by the various technics might suggest a multiplicity of inhibitors it is felt that it rather denotes a greater sensitivity of the adsorption technic as compared to the others.

scholarly journals Metabolic Requirements for Spermatogonial Stem Cell Establishment and Maintenance In Vivo and In Vitro

2021 ◽  
Vol 22 (4) ◽  
pp. 1998
Author(s):  
Anna Laura Voigt ◽  
Shiama Thiageswaran ◽  
Nathalia de Lima e Martins Lara ◽  
Ina Dobrinski
Keyword(s):  
Stem Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Adult Stem Cell ◽  
Spermatogonial Stem Cell ◽  
Testicular Development ◽  
Cell Integrity ◽  
In Vitro Expansion

The spermatogonial stem cell (SSC) is a unique adult stem cell that requires tight physiological regulation during development and adulthood. As the foundation of spermatogenesis, SSCs are a potential tool for the treatment of infertility. Understanding the factors that are necessary for lifelong maintenance of a SSC pool in vivo is essential for successful in vitro expansion and safe downstream clinical usage. This review focused on the current knowledge of prepubertal testicular development and germ cell metabolism in different species, and implications for translational medicine. The significance of metabolism for cell biology, stem cell integrity, and fate decisions is discussed in general and in the context of SSC in vivo maintenance, differentiation, and in vitro expansion.

scholarly journals Author Correction: The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nagasuryaprasad Kotikalapudi ◽  
Samuel Joshua Pragasam Sampath ◽  
Sinha Sukesh Narayan ◽  
Bhonde R. ◽  
Harishankar Nemani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
In Vitro Model ◽  
Model Systems ◽  
Mesenchymal Stem Cell Therapy ◽  
Preclinical Diabetes ◽  
Vitro Model

scholarly journals Current and Future Antiviral Strategies to Tackle Gastrointestinal Viral Infections

2021 ◽  
Vol 9 (8) ◽  
pp. 1599
Author(s):  
Nanci Santos-Ferreira ◽  
Jana Van Dycke ◽  
Johan Neyts ◽  
Joana Rocha-Pereira
Keyword(s):  
Viral Infections ◽  
Current Knowledge ◽  
Model Systems ◽  
Viral Gastroenteritis ◽  
Library Screening ◽  
Natural Sources ◽  
Repurposed Drugs ◽  
Enteric Adenoviruses

Acute gastroenteritis caused by virus has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The main culprits are rotaviruses, noroviruses, sapoviruses, astroviruses, and enteric adenoviruses. Currently, there are no antiviral drugs available for the prevention or treatment of viral gastroenteritis. Here, we describe the antivirals that were identified as having in vitro and/or in vivo activity against these viruses, originating from in silico design or library screening, natural sources or being repurposed drugs. We also highlight recent advances in model systems available for this (hard to cultivate) group of viruses, such as organoid technologies, and that will facilitate antiviral studies as well as fill some of current knowledge gaps that hamper the development of highly efficient therapies against gastroenteric viruses.

scholarly journals mSphere of Influence: Understanding Virus-Host Interactions Requires a Multifaceted Approach

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Rory D. de Vries
Keyword(s):  
Measles Virus ◽  
Ex Vivo ◽  
Viral Pathogenesis ◽  
Model Systems ◽  
Host Immune System ◽  
Recombinant Viruses ◽  
Host Interactions ◽  
Link Type

ABSTRACT Rory de Vries works in the field of viral pathogenesis and focuses on interactions between respiratory viruses (or corresponding vaccines) and the host immune system. In this mSphere of Influence article, he reflects on how the articles “Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques” by R. L. de Swart et al. (R. L. de Swart, M. Ludlow, L. de Witte, Y. Yanagi, et al., PLoS Pathog 3:e178, 2007, https://doi.org/10.1371/journal.ppat.0030178) and “Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality” by M. J. Mina et al. (M. J. Mina, C. J. Metcalf, R. L. de Swart, A. D. M. E. Osterhaus, and B. T. Grenfell, Science 348:694–699, 2015, https://doi.org/10.1126/science.aaa3662) made an impact on him. These articles studied interactions between measles virus and the host and influenced him by making two important points. (i) It is crucial to use nonadapted (recombinant) viruses in disease-relevant model systems when studying virus-host interactions. (ii) Studying viral pathogenesis requires a combination of in vitro, ex vivo, and in vivo studies, and a group of researchers with multiple expertises. He learned that only when all these aspects are combined, can one truly answer the question: “How does a virus cause disease?”

scholarly journals Modeling Hepatotropic Viral Infections: Cells vs. Animals

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1726
Author(s):  
Niloofar Khoshdel-Rad ◽  
Ensieh Zahmatkesh ◽  
Polina Bikmulina ◽  
Maria Peshkova ◽  
Nastasia Kosheleva ◽  
...  
Keyword(s):  
Viral Hepatitis ◽  
Viral Infections ◽  
Model Systems ◽  
Hepatitis Viruses ◽  
Major Health ◽  
Intracellular Parasites ◽  
In Vivo Animal Models ◽  
Efficient Viral Replication

The lack of an appropriate platform for a better understanding of the molecular basis of hepatitis viruses and the absence of reliable models to identify novel therapeutic agents for a targeted treatment are the two major obstacles for launching efficient clinical protocols in different types of viral hepatitis. Viruses are obligate intracellular parasites, and the development of model systems for efficient viral replication is necessary for basic and applied studies. Viral hepatitis is a major health issue and a leading cause of morbidity and mortality. Despite the extensive efforts that have been made on fundamental and translational research, traditional models are not effective in representing this viral infection in a laboratory. In this review, we discuss in vitro cell-based models and in vivo animal models, with their strengths and weaknesses. In addition, the most important findings that have been retrieved from each model are described.

scholarly journals The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nagasuryaprasad Kotikalapudi ◽  
Samuel Joshua Pragasam Sampath ◽  
Sinha Sukesh Narayan ◽  
Bhonde Ramesh R ◽  
Harishankar Nemani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Clinical Success ◽  
Significant Risk ◽  
Stromal Vascular Fraction ◽  
Significant Risk Factor ◽  
Model Systems ◽  
Mesenchymal Stem Cell Therapy

AbstractObesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in  pre-clinical/Ob-T2D management.

scholarly journals Mechanistic and therapeutic distinctions between cardiosphere-derived cell and mesenchymal stem cell extracellular vesicle non-coding RNA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ann-Sophie Walravens ◽  
Sasha Smolgovsky ◽  
Liang Li ◽  
Lauren Kelly ◽  
Travis Antes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Efficacy ◽  
Adult Stem Cell ◽  
Extracellular Vesicle ◽  
Parent Cell ◽  
Opposite Pattern ◽  
Acute Peritonitis ◽  
Non Coding Rna

AbstractCell therapy limits ischemic injury following myocardial infarction (MI) by preventing cell death, modulating the immune response, and promoting tissue regeneration. The therapeutic efficacy of cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs) is associated with extracellular vesicle (EV) release. Prior head-to-head comparisons have shown CDCs to be more effective than MSCs in MI models. Despite differences in cell origin, it is unclear why EVs from different adult stem cell populations elicit differences in therapeutic efficacy. Here, we compare EVs derived from multiple human MSC and CDC donors using diverse in vitro and in vivo assays. EV membrane protein and non-coding RNA composition are highly specific to the parent cell type; for example, miR-10b is enriched in MSC-EVs relative to CDC-EVs, while Y RNA fragments follow the opposite pattern. CDC-EVs enhance the Arg1/Nos2 ratio in macrophages in vitro and reduce MI size more than MSC-EVs and suppress inflammation during acute peritonitis in vivo. Thus, CDC-EVs are distinct from MSC-EVs, confer immunomodulation, and protect the host against ischemic myocardial injury and acute inflammation.

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