Animal Cell Culture Research Articles

Editorial and News

Editorial and News

Screening for Deleterious non-synonymous SNPs in Human CCL21 Gene using in-silico analysis

Rheumatoid arthritis (RA) is a chronic, systematic, and progressive inflammatory disorder, causing severe damage to joints and hence increase mortality. The Chemokine (C-C motif) ligand 21 (CCL21), a member cytokines family, is involved in immuno-inflammatory and regulatory processes. Therefore, identifying the important SNPs (single nucleotide polymorphisms) in the CCL21 gene is of key importance to evaluate their structural and functional significance and to discover novel therapeutic targets for immune-related diseases, including RA. In this study, we used in silico approaches for identifying the most damaging non-synonymous SNPs (nsSNPs), playing a significant structural and functional role in CCL21 protein. The primary tools used for this study included PROVEAN, SNPs&GO, SIFT and PolyPhen2. Other tools, its stability, Structure and functional effect as well as the conservation profile, were verified using I-Mutant, MutPred, and ConSurf. The site of post-translational modification also predicted. The 3-D modeling of proteins was carried out using I-TASSER which were then visualized in Chimera v1.11. Furthermore, the gene-gene interactions were predicted using STRING and gene MANIA. It was observed that the nsSNPs D30Y (rs753133670), I62N (rs1170851787), R75C (rs759733358), R75S (rs776954599) and A83V (rs776954599) were the most damaging nsSNPs in the CCL21 gene. These nsSNPs might have a significant role in CCL2 protein’s malfunctioning and possibly causing different autoimmune diseases including RA. Our study concluded that, to study the correlation of the CCL21 gene with certain autoimmune disorders, i.e. Crohn’s Disease (CD), RA and other immune-associated diseases, these SNPs could be the most important ones. In addition, these SNPs need to be studied in animal models and cell cultures in association with certain diseases, to identify if they could be of use for the gene therapy and pharmacogenomics.

Oridonin Ameliorates Traumatic Brain Injury-Induced Neurological Damage by Improving Mitochondrial Function and Antioxidant Capacity and Suppressing Neuroinflammation through the Nrf2 Pathway.

Traumatic brain injury (TBI) is a global public health concern, and few effective treatments for its delayed damages are available. Oridonin (Ori) recently has been reported to show a promising neuroprotective efficacy, but its potential therapeutic effect on TBI has not been thoroughly elucidated. The TBI mouse models were established and treated with Ori or vehicle 30 min post-operation and every 24 h since then. Impairments in cognitive and motor function and neuropathological changes were evaluated and compared. The therapeutic efficacy and mechanisms of action of Ori were further investigated using animal tissues and cell cultures. Ori restored motor function and cognition after TBI-induced impairment and exerted neuroprotective effects by reducing cerebral edema and cortical lesion volume. Ori increased neuronal survival, ameliorating gliosis and the accumulation of macrophages after injury. It suppressed the increased production of reactive oxygen species, lipid peroxide, and malondialdehyde and reversed the decrease of mitochondrial membrane potential and adenosine triphosphate content, which was also identified in oxidatively stressed neuronal cultures. Further, Ori inhibited the expression of nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) inflammasome proteins and NLRP3-dependent cytokine interleukin-1β that can be induced by oxidative stress after TBI. Regarding underlying mechanisms, Ori significantly enhanced expression of key proteins of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. Our results demonstrated that Ori effectively improved functional impairments and neuropathological changes in animals with TBI. By activating the Nrf2 pathway, it improved mitochondrial function and antioxidant capacity and suppressed the neuroinflammation induced by oxidative stress. The results therefore suggest Ori as a potent candidate for managing neurological damage after TBI.

Proliferation and differentiation of primary bovine myoblasts using Chlorella vulgaris extract for sustainable production of cultured meat

Recently, cultured meat obtained from livestock-derived cells is being considered as a sustainable food source that reduces the use of natural resources. This study aimed to show that nutrients extracted from Chlorella vulgaris were beneficial in the culture of primary bovine myoblasts (PBMs), a major cell source for cultured meat production. Nutrients (glucose, amino acids, and vitamins) present in the animal-cell culture media were effectively recovered from C. vulgaris using acid hydrolysis treatment. On culture in nutrient-free inorganic salt solution, cell death was induced in most PBMs after 6 days of cultivation. However, the addition of C. vulgaris extract (CVE) significantly improved PBM viability, which was comparable to the viability in conventional culture medium (Dulbecco's modified Eagle's medium). Furthermore, by adding horse serum to induce differentiation, the formation of myotubes was confirmed when CVE were used. Together, the results showed that CVE could be used as an alternative to the conventional culture medium for PBMs. These findings will not only lower the environmental risks associated with the establishment of this eco-friendly cell culture system, but also highlight microalgae as a potent nutrient source that can replace conventional grain-dependent nutrient sources.

Optimization of measurement of mitochondrial electron transport activity in postmortem human brain samples and measurement of susceptibility to rotenone and 4-hydroxynonenal inhibition

Mitochondrial function is required to meet the energetic and metabolic requirements of the brain. Abnormalities in mitochondrial function, due to genetic or developmental factors, mitochondrial toxins, aging or insufficient mitochondrial quality control contribute to neurological and psychiatric diseases. Studying bioenergetics from postmortem human tissues has been challenging due to the diverse range of human genetics, health conditions, sex, age, and postmortem interval. Furthermore, fresh tissues that were in the past required for assessment of mitochondrial respiratory function were rarely available. Recent studies established protocols to use in bioenergetic analyses from frozen tissues using animal models and cell cultures. In this study we optimized these methods to determine the activities of mitochondrial electron transport in postmortem human brain. Further we demonstrate how these samples can be used to assess the susceptibility to the mitochondrial toxin rotenone and exposure to the reactive lipid species 4-hydroxynonenal. The establishment of such an approach will significantly impact translational studies of human diseases by allowing measurement of mitochondrial function in human tissue repositories.

Blueberries and health

Blueberry is a high value crop globally. Both wild and cultivated blueberries are commercially available to consumers. Although mostly consumed as fresh or frozen, dried blueberries are also offered in the market. Yogurts, beverages, jams, and jellies made with blueberries are some of the products popular with consumers.Blueberries are rich in several health-beneficial phytochemicals including phenolic compounds and vitamins. This article reviews the health implications of blueberry consumption. The review was limited to the research studies published in peer-reviewed scientific journals. The impact of blueberry intake on cardiovascular functions, obesity, cancer, diabetes, cognitive performance, and gut microbiota was the focus of this review.This review clearly revealed very broad health benefits of blueberry intake. However, it is evident that scientific studies on this topic are scarce. Indeed, there are only a few studies on the health effects of blueberries published in scientific journals. The majority of the investigations on this topic were carried out using animal models or cell cultures. Scarcity and limited size of the clinical studies in this field leave many questions about the effect of blueberry consumption on human health unanswered. Undoubtedly, there is a need for large-scale controlled and randomized clinical and epidemiological studies and meta-analyses of the data from such research. This would allow for an in-depth understanding of the effect of blueberries on health and the biological and metabolic pathways involved in disease mitigation and treatment.Keywords: Blueberry, cancer, cardiovascular health, chemical composition, cognitive performance, diabetes, gut microbiota, obesity, phytochemicals

The Structure of T-DNA Insertions in Transgenic Tobacco Plants Producing Bovine Interferon-Gamma

Many of the most modern drugs are of a protein nature and are synthesized by transgenic producer organisms. Bacteria, yeast, or animal cell cultures are commonly used, but plants have a number of advantages—minimal biomass unit cost, animal safety (plants are not attacked by mammalian pathogens), the agricultural scale of production, and the ability to produce complex proteins. A disadvantage of plants may be an unstable level of transgene expression, which depends on the transgene structure and its insertion site. We analyzed the structure of T-DNA inserts in transgenic tobacco plants (Nicotiana tabacum L.) belonging to two lines obtained using the same genetic construct but demonstrating different biological activities of the recombinant protein (bovine interferon-gamma). We found that, in one case, T-DNA was integrated into genomic DNA in the region of centromeric repeats, and in the other, into a transcriptionally active region of the genome. It was also found that in one case, the insert has a clustered structure and consists of three copies. Thus, the structure of T-DNA inserts in both lines is not optimal (the optimal structure includes a single copy of the insert located in the active region of the genome). It is desirable to carry out such studies at the early stages of transgenic plants selection.

Generation of Porcine Induced Neural Stem Cells Using the Sendai Virus.

The reprogramming of cells into induced neural stem cells (iNSCs), which are faster and safer to generate than induced pluripotent stem cells, holds tremendous promise for fundamental and frontier research, as well as personalized cell-based therapies for neurological diseases. However, reprogramming cells with viral vectors increases the risk of tumor development due to vector and transgene integration in the host cell genome. To circumvent this issue, the Sendai virus (SeV) provides an alternative integration-free reprogramming method that removes the danger of genetic alterations and enhances the prospects of iNSCs from bench to bedside. Since pigs are among the most successful large animal models in biomedical research, porcine iNSCs (piNSCs) may serve as a disease model for both veterinary and human medicine. Here, we report the successful generation of piNSC lines from pig fibroblasts by employing the SeV. These piNSCs can be expanded for up to 40 passages in a monolayer culture and produce neurospheres in a suspension culture. These piNSCs express high levels of NSC markers (PAX6, SOX2, NESTIN, and VIMENTIN) and proliferation markers (KI67) using quantitative immunostaining and western blot analysis. Furthermore, piNSCs are multipotent, as they are capable of producing neurons and glia, as demonstrated by their expressions of TUJ1, MAP2, TH, MBP, and GFAP proteins. During the reprogramming of piNSCs with the SeV, no induced pluripotent stem cells developed, and the established piNSCs did not express OCT4, NANOG, and SSEA1. Hence, the use of the SeV can reprogram porcine somatic cells without first going through an intermediate pluripotent state. Our research produced piNSCs using SeV methods in novel, easily accessible large animal cell culture models for evaluating the efficacy of iNSC-based clinical translation in human medicine. Additionally, our piNSCs are potentially applicable in disease modeling in pigs and regenerative therapies in veterinary medicine.

CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10.

Understanding the hydrodynamic conditions in bioreactors is of utmost importance for the selection of operating conditions during cell culture process development. In the present study, the two-phase flow in the lab-scale single-use bioreactor Xcellerex XDR-10 is characterized for working volumes from 4.5 L to 10 L, impeller speeds from 40 rpm to 360 rpm, and sparging with two different microporous spargers at rates from 0.02 L min to 0.5 L min. The numerical simulations are performed with the one-way coupled Euler–Lagrange and the Euler–Euler models. The results of the agitated liquid height, the mixing time, and the volumetric oxygen mass transfer coefficient are compared to experiments. For the unbaffled XDR-10, strong surface vortex formation is found for the maximum impeller speed. To support the selection of suitable impeller speeds for cell cultivation, the surface vortex formation, the average turbulence energy dissipation rate, the hydrodynamic stress, and the mixing time are analyzed and discussed. Surface vortex formation is observed for the maximum impeller speed. Mixing times are below 30 s across all conditions, and volumetric oxygen mass transfer coefficients of up to 22.1 h are found. The XDR-10 provides hydrodynamic conditions which are well suited for the cultivation of animal cells, despite the unusual design of a single bottom-mounted impeller and an unbaffled cultivation bioreactor.

Is the development of low-cost media one of the greatest challenges to produce cultivated meat on an industrial scale?

Cultivated meat (CM) has emerged as an “ethical” alternative for the consumption of meat, avoiding animal slaughter and safeguarding animal care. The idea behind animal cell cultivation, differentiation and proliferation is old, but the investments, technological developments and first efforts to produce CM on industrial scale are very recent. There are many challenges and bottlenecks within this new market, including social, environmental, technological, regulatory and logistic aspects; however, the emphasis of this article is the composition of the culture media for animal cells development, which is strongly attached to economy (component costs) and ethics (components of animal origin). Traditional basal media (such as Eagle´s Minimum Essential Medium and Ham´s F-12) comprise energy and carbon sources, vitamins, amino acids and trace elements; but the requirements for development and differentiation of skeletal muscle cells demand other components of animal origin, such as fetal bovine serum and/or other growth factors, hormones and inducers. Recent articles and patents have reported the substitution of these components, including the use of recombinant albumin, postbiotics, and microalgal extracts. Despite these efforts, the current market of CM is still in its “first childhood” with 107 enterprises around the world, and just a few of them are authorized to commercialize CM; the current price to the final consumer is, in the best case, 7.5 times higher when compared to traditional meat. Therefore, from our point of view, there is still a long way to go in developing this new product and establishing a new global market.

A Simulation Analysis of an Influenza Vaccine Production Plant in Areas of High Humanitarian Flow. A Preliminary Study for the Region of Norte de Santander (Colombia)

The production of vaccines of biological origin presents a tremendous challenge for researchers. In this context, animal cell cultures are an excellent alternative for the isolation and production of biologicals against several viruses, since they have an affinity with viruses and a great capacity for their replicability. Different variables have been studied to know the system’s ideal parameters, allowing it to obtain profitable and competitive products. Consequently, this work focuses its efforts on evaluating an alternative for producing an anti-influenza biological from MDCK cells using SuperPro Designer v8.0 software. The process uses the DMEN culture medium supplemented with nutrients as raw material for cell development; the MDCK cells were obtained from a potential scale-up with a final working volume of 500 L, four days of residence time, inoculum volume of 10%, and continuous working mode with up to a total of 7400 h/Yr of work. The scheme has the necessary equipment for the vaccine’s production, infection, and manufacture with yields of up to 416,698 units/h. In addition, it was estimated to be economically viable to produce recombinant vaccines with competitive prices of up to 0.31 USD/unit.

Modulatory Role of Carbon Monoxide on the Inflammatory Response and Oxidative Stress Linked to Gastrointestinal Disorders.

Significance: Carbon monoxide (CO) is an endogenous gaseous mediator that plays an important role in maintaining gastrointestinal (GI) tract homeostasis, acting in mucosal defense, and providing negative modulation of pathophysiological markers of clinical conditions. Recent Advances: Preclinical studies using animal models and/or cell culture show that CO can modulate the inflammatory response and oxidative stress in GI mucosal injuries and pathological conditions, reducing proinflammatory cytokines and reactive oxygen species, while increasing antioxidant defense mechanisms. Critical Issues: CO has potent anti-inflammatory and antioxidant effects. The defense mechanisms of the GI tract are subject to aggression by different chemical agents (e.g., drugs and ethanol) as well as complex and multifactorial diseases, with inflammation and oxidative stress as strong triggers for the deleterious effects. Thus, it is possible that CO acts on a variety of molecules involved in the inflammatory and oxidative signaling cascades, as well as reinforcing several defense mechanisms that maintain GI homeostasis. Future Directions: CO-based therapies are promising tools for the treatment of GI disorders, such as gastric and intestinal injuries, inflammatory bowel disease, and pancreatitis. Therefore, it is necessary to develop safe and selective CO-releasing agents and/or donor drugs to facilitate effective treatments and methods for analysis of CO levels that are simple and inexpensive. Antioxid. Redox Signal. 37, 98-114.

Simulation and modeling of physiological processes of vital organs in organ-on-a-chip biosystem

The limited adequacy of animal cell cultures and models to mimic the complexity of human bodies in laboratory conditions has emphasized researchers to find its quintessential bioelectronic alternative with improved competence. In this regard, tissue engineering has emerged as one of the most precise biomaterial technologies in terms of creating new tissues to model vital organs. An organ-on-a-chip biosystem has shown a plethora of applications in tissue engineering and drug delivery. Organ-on-a-chip is a microfluidic device that provides a completely controlled microenvironment, similar to the natural tissues for the cultured cells of an organ, by amalgamating cell biology and biomaterial science. The device contains several microchambers and microchannels embedded in a layer of a biocompatible polymer, such as polydimethylsiloxane. Microchambers house the cells, while microchannels provide nutrients and growth factors. Over the past few years, organ-on-a-chip technology has displayed ample applications in the field of biomedicine, not only by simulating the normal functions of disparate organs, but also by understanding the inter-relation between diversified systems. In this review, we have spotlighted recent advancements and applications of organ-on-a-chip biosystems to construct physiological models for the heart, lung, kidney, liver, and brain. Part of this review is also concentrated on abridging the desperate essentiality as well as future perspectives of organ-on-a-chip technology in biomedicine, disease modeling, and drug development process.

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy.

Although the neurotoxicity of ZnO nanoparticles (NPs) has been evaluated in animal and nerve cell culture models, these models cannot accurately mimic human brains. Three-dimensional (3D) brain organoids based on human-induced pluripotent stem cells have been developed to study the human brains, but this model has rarely been used to evaluate NP neurotoxicity. We used 3D brain organoids that express cortical layer proteins to investigate the mechanisms of ZnO NP-induced neurotoxicity. Cytotoxicity caused by high levels of ZnO NPs (64μg/mL) correlated with high intracellular Zn ion levels but not superoxide levels. Exposure to a non-cytotoxic concentration of ZnO NPs (16μg/mL) increased the autophagy-marker proteins LC3B-II/I but decreased p62 accumulation, whereas a cytotoxic concentration of ZnO NPs (64μg/mL) decreased LC3B-II/I proteins but did not affect p62 accumulation. Fluorescence micro-optical sectioning tomography revealed that 64μg/mL ZnO NPs led to decreases in LC3B proteins that were more obvious at the outer layers of the organoids, which were directly exposed to the ZnO NPs. In addition to reducing LC3B proteins in the outer layers, ZnO NPs increased the number of micronuclei in the outer layers but not the inner layers (where LC3B proteins were still expressed). Adding the autophagy flux inhibitor bafilomycin A1 to ZnO NPs increased cytotoxicity and intracellular Zn ion levels, but adding the autophagy inducer rapamycin only slightly decreased cellular Zn ion levels. We conclude that high concentrations of ZnO NPs are cytotoxic to 3D brain organoids via defective autophagy and intracellular accumulation of Zn ions.

Vaccine Production

Introduction Vaccines are biological products that elicit a protective immune response. The details of the manufacturing processes are varied depending on the particular characteristics of the vaccine. There are classically, three basic types of vaccines against viral and bacterial pathogens (For mRNA-, DNA- and vector-vaccines see Chapters 7, 8, 9): Live-attenuated. Killed (non-live). Subunit. “Classical” Vaccine Production The basic classical process includes 5 phases: expression, harvest, inactivation, purification, formulation. The expression systems for viral and bacterial vaccines are distinct. Bacterial expression is performed in fermenters. Viral vaccines are produced in animal cell culture or embryonated chicken eggs. Processes for whole viral or bacterial vaccines often involve only limited processing after expression. Subunit vaccines routinely require the most purification to separate the product from other contaminants. Challenges Challenges for bacterial vaccines include testing to ensure the safety and efficacy of the product. Inactivation procedures need to be carefully controlled. Live attenuated vaccines need to be tested to ensure the vaccine strains are still safe and effective. Viral vaccines require testing to ensure foreign infectious agents are not introduced during processing. Both cultured cells and egg present risks for infection. Live viral vaccines and gene vectors need to be carefully engineered and tested to minimize safety concerns. Highly variable vaccine targets such as influenza need to be re-adapted to current circulating strains.

Numerical and experimental characterization of the single-use bioreactor Xcellerex™ XDR-200

The optimization of operating conditions is vital for cell culture process development. In the present study, the pilot-scale single-use bioreactor Xcellerex™ XDR-200, which is typically used in cell culture scale-up, is investigated. This unbaffled reactor is equipped with an off-centered, bottom mounted impeller, and has a maximum working volume of 200 L. The flow field for this sparsely investigated bioreactor configuration is studied with computational fluid dynamics. Moreover, numerical simulations of the mixing time and the volumetric oxygen mass transfer coefficient for seven different test conditions are validated against experimental data. Mixing times across all tested conditions are found to remain below 30 s, and the volumetric oxygen mass transfer coefficient is between 2.0 and 20.0 h−1, which is a typical range for animal cell culture processes. These values of the oxygen transfer coefficient are found for as low as 0.004–0.125 L L−1 min−1 sparging rates with the microporous sparger. The hydrodynamic stress remains below critical values for cell damage for all conditions investigated. Vortex formation is suppressed in the bioreactor even though it is unbaffled due to off-centered impeller. Across the test conditions, the highest investigated impeller speed of 200 rpm is the most favorable due to fast mixing and high oxygen transfer.

Contesting and reinforcing the future of ‘meat’ through problematization: Analyzing the discourses in regulatory debates around animal cell-cultured meat

This paper draws attention to how ‘problems’ were constructed at the USDA-FDA Joint Public Meeting on Use of Animal Cell Culture Technology in 2018 and the implications of these discursive constructs for the governance of animals in food systems. The findings demonstrate what problems animal cell-cultured meat has been positioned as the solution to, and what problems emerge from this new technology that regulators are expected to respond to. The problem representation and the solutions posed reproduce understandings that normalize and promote high and increasing levels of animal flesh consumption and related intensive uses of animals. With relevance for various academic disciplines, and policy-making and activist communities, this analysis offers insight from a critical animal studies lens into the role discourse plays in the governance of food systems that in turn shape the lives and bodies of animals in this emerging regulatory space.

Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation.

Background: Intervention of neuroinflammation in central nervous system (CNS) represents a potential therapeutic strategy for a host of brain disorders. The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in the Orient to treat inflammation-related diseases such as rhumatoid arthritis and chronic pain. Scorpion venom heat-resistant peptide (SVHRP), a component from BmK venom, has been shown to reduce seizure susceptibility in a rat epileptic model and protect against cerebral ischemia-reperfusion injury. As neuroinflammation has been implicated in chronic neuronal hyperexcitability, epileptogenesis and cerebral ischemia-reperfusion injury, the present study aimed to investigate whether SVHRP has anti-inflammatory property in brain. Methods: An animal model of neuroinflammation induced by lipopolysacchride (LPS) injection was employed to investigate the effect of SVHRP (125 µg/kg, intraperitoneal injection) on inflammagen-induced expression of pro-inflammatory factors and microglia activation. The effect of SVHRP (2–20 μg/ml) on neuroinflammation was further investigated in primary brain cell cultures containing microglia as well as the immortalized BV2 microglia culture stimulated with LPS. Real-time quantitative PCR were used to measure mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in hippocampus of animals. Protein levels of TNF-α, iNOS, P65 subunit of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were examined by ELISA or western blot. Microglia morphology in animal hippocampus or cell cultures and cellular distribution of p65 were shown by immunostaining. Results: Morphological study demonstrated that activation of microglia, the main component that mediates the neuroinflammatory process, was inhibited by SVHRP in both LPS mouse and cellular model. Our results also showed dramatic increases in the expression of iNOS and TNF-α in hippocampus of LPS-injected mice, which was significantly attenuated by SVHRP treatment. In vitro results showed that SVHRP attenuated LPS-elicited expression of iNOS and TNF-α in different cultures without cell toxicity, which might be attributed to suppression of NF-κB and MAPK pathways by SVHRP. Conclusion: Our study demonstrates that SVHRP is able to inhibit neuroinflammation and microglia activation, which may underlie the therapeutic effects of BmK-derived materials, suggesting that BmK venom could be a potential source for CNS drug development.

Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.

Harness Organoid Models for Virological Studies in Animals: A Cross-Species Perspective.

Animal models and cell culture in vitro are primarily used in virus and antiviral immune research. Whereas the limitation of these models to recapitulate the viral pathogenesis in humans has been made well aware, it is imperative to introduce more efficient systems to validate emerging viruses in both domestic and wild animals. Organoids ascribe to representative miniatures of organs (i.e., mini-organs), which are derived from three-dimensional culture of stem cells under respective differential conditions mimicking endogenous organogenetic niches. Organoids have broadened virological studies in the human context, particularly in recent uses for COVID19 research. This review examines the status and potential for cross-species applied organotypic culture in validating emerging animal, particularly zoonotic, viruses in domestic and wild animals.