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Translational Vision Science &... Jun 2023The purpose of this study was to construct an animal model of Graves' ophthalmopathy (GO) by comparing recombinant adenovirus expressing human thyrotropin receptor A...
PURPOSE
The purpose of this study was to construct an animal model of Graves' ophthalmopathy (GO) by comparing recombinant adenovirus expressing human thyrotropin receptor A subunit (Ad-TSHR A) gene immunization and dendritic cell (DC) immunization. We evaluated the animal models that are closer to the pathology of human GO, and laid the foundation for the study of GO.
MATERIALS AND METHODS
Ad-TSHR A was injected intramuscularly into female BALB/c mice to induce the GO animal model. A GO animal model was constructed using TSHR combined with IFN-γ-modified primary DC immunized female BALB/c. The animal models constructed by the above two methods were evaluated in terms of ocular appearance, serology, pathology, and imaging to assess the modeling rate of the animal models, respectively.
RESULTS
Both modeled mice exhibited increased serological indexes of free thyroxine (FT4) and TSH receptor antibodies (TRAbs) levels and decreased TSH (P < 0.01). Thyroid pathology analysis revealed the number of thyroid follicles increases, the size varies, and the follicular epithelial cells proliferate to varying degrees in a cuboidal or tall columnar pattern, with a small amount of lymphocytic infiltration visible. Adipose tissue behind the eyeball was accumulated, the muscle outside the eyeball was broken and fibrotic, and hyaluronic acid (HA) behind the eyeball was increased. The animal model of GO constructed by immunization of TSHR with IFN-γ-modified DC had a modeling rate of 60%, whereas that of Ad-TSHR A gene immunization was 72%.
CONCLUSIONS
Both gene immunization and cellular immunization can be used to construct GO models, and the modeling rate of gene immunization is higher than that of cellular immunization.
TRANSLATIONAL RELEVANCE
In this study, two innovative methods, cellular immunity and gene immunity, were used to establish GO animal models, which improved the success rate to a certain extent. To our knowledge, this study presents the first cellular immunity modeling idea of TSHR combined with IFN-γ for the GO animal model, which provides an animal model basis for understanding the pathogenesis of GO and developing new treatment methods.
Topics: Female; Mice; Animals; Humans; Graves Ophthalmopathy; Disease Models, Animal; Eye; Receptors, Thyrotropin; Mice, Inbred BALB C
PubMed: 37342053
DOI: 10.1167/tvst.12.6.12 -
Comparative Medicine Jun 2017Animal models are vital in understanding the transmission and pathogenesis of infectious organisms and the host immune response to infection. In addition, animal models... (Review)
Review
Animal models are vital in understanding the transmission and pathogenesis of infectious organisms and the host immune response to infection. In addition, animal models are essential in vaccine and therapeutic drug development and testing. Prior to selecting an animal model to use when studying an infectious agent, the scientific team must determine that sufficient in vitro and ex vivo data are available to justify performing research in an animal model, that ethical considerations are addressed, and that the data generated from animal work will add useful information to the body of scientific knowledge. Once it is established that an animal should be used, the questions become 'Which animal model is most suitable?' and 'Which experimental design issues should be considered?' The answers to these questions take into account numerous factors, including scientific, practical, welfare, and regulatory considerations, which are the focus of this article.
Topics: Animal Experimentation; Animal Welfare; Animals; Communicable Diseases; Disease Models, Animal; Disease Transmission, Infectious; Research Design
PubMed: 28662751
DOI: No ID Found -
Animal Models and Experimental Medicine Mar 2021
Topics: Animals; Biomedical Research; COVID-19; Models, Animal; SARS-CoV-2
PubMed: 33738431
DOI: 10.1002/ame2.12156 -
ILAR Journal Dec 2021There is no prescribed stage or standardized point at which an animal model protocol is reviewed for reproducibility and translatability. The method of review for a... (Review)
Review
There is no prescribed stage or standardized point at which an animal model protocol is reviewed for reproducibility and translatability. The method of review for a reproducible and translatable study is not consistently documented in peer literature, and this is a major challenge for those working with animal models of human diseases. If the study is ill designed, it is impossible to perform an accurate harm/benefit analysis. In addition, there may be an ethical challenge if the work is not reproducible and translatable. Animal welfare regulations and other documents of control clearly state the role of the Institutional Animal Care and Use Committees are to look at science justification within the context of animal welfare. This article, concentrating on models not governed by regulations, outlines issues and offers recommendations for refining animal model review with a goal to improve study reproducibility and translatability.
Topics: Animal Care Committees; Animal Experimentation; Animal Welfare; Animals; Models, Animal; Reproducibility of Results
PubMed: 33693624
DOI: 10.1093/ilar/ilaa027 -
Advances in Wound Care Aug 2022Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and... (Review)
Review
Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field. Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability. The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema. As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.
Topics: Animals; Disease Models, Animal; Humans; Lymphatic System; Lymphatic Vessels; Lymphedema; Reproducibility of Results
PubMed: 34128396
DOI: 10.1089/wound.2021.0033 -
Drug Design, Development and Therapy 2014Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the... (Review)
Review
Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients.
Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Humans; Molecular Targeted Therapy; Neoplasms; Neoplasms, Experimental
PubMed: 25342884
DOI: 10.2147/DDDT.S49584 -
American Journal of Physiology. Renal... Jun 2021Pigs represent a potentially attractive model for medical research. Similar body size and physiological patterns of kidney injury that more closely mimic those described...
Pigs represent a potentially attractive model for medical research. Similar body size and physiological patterns of kidney injury that more closely mimic those described in humans make larger animals attractive for experimentation. Using larger animals, including pigs, to investigate the pathogenesis of acute kidney injury (AKI) also serves as an experimental bridge, narrowing the gap between clinical disease and preclinical discoveries. This article compares the advantages and disadvantages of large versus small AKI animal models and provides a comprehensive overview of the development and application of porcine models of AKI induced by clinically relevant insults, including ischemia-reperfusion, sepsis, and nephrotoxin exposure. The primary focus of this review is to evaluate the use of pigs for AKI studies by current investigators, including areas where more information is needed.
Topics: Acute Kidney Injury; Animals; Disease Models, Animal; Swine
PubMed: 33900853
DOI: 10.1152/ajprenal.00022.2021 -
Experimental Physiology May 2023What is the central question of this study? Invasive cardiovascular instrumentation can occur through closed- or open-chest approaches. To what extent will sternotomy...
NEW FINDINGS
What is the central question of this study? Invasive cardiovascular instrumentation can occur through closed- or open-chest approaches. To what extent will sternotomy and pericardiotomy affect cardiopulmonary variables? What is the main finding and its importance? Opening of the thorax decreased mean systemic and pulmonary pressures. Left ventricular function improved, but no changes were observed in right ventricular systolic measures. No consensus or recommendation exists regarding instrumentation. Methodological differences risk compromising rigour and reproducibility in preclinical research.
ABSTRACT
Animal models of cardiovascular disease are often evaluated by invasive instrumentation for phenotyping. As no consensus exists, both open- and closed-chest approaches are used, which might compromise rigour and reproducibility in preclinical research. We aimed to quantify the cardiopulmonary changes induced by sternotomy and pericardiotomy in a large animal model. Seven pigs were anaesthetized, mechanically ventilated and evaluated by right heart catheterization and bi-ventricular pressure-volume loop recordings at baseline and after sternotomy and pericardiotomy. Data were compared by ANOVA or the Friedmann test where appropriate, with post-hoc analyses to control for multiple comparisons. Sternotomy and pericardiotomy caused reductions in mean systemic (-12 ± 11 mmHg, P = 0.027) and pulmonary pressures (-4 ± 3 mmHg, P = 0.006) and airway pressures. Cardiac output decreased non-significantly (-1329 ± 1762 ml/min, P = 0.052). Left ventricular afterload decreased, with an increase in ejection fraction (+9 ± 7%, P = 0.027) and coupling. No changes were observed in right ventricular systolic function or arterial blood gases. In conclusion, open- versus closed-chest approaches to invasive cardiovascular phenotyping cause a systematic difference in key haemodynamic variables. Researchers should adopt the most appropriate approach to ensure rigour and reproducibility in preclinical cardiovascular research.
Topics: Swine; Animals; Pericardiectomy; Sternotomy; Reproducibility of Results; Hemodynamics; Models, Animal
PubMed: 36892095
DOI: 10.1113/EP090919 -
Progress in building clinically relevant patient-derived tumor xenograft models for cancer research.Animal Models and Experimental Medicine Oct 2023Patient-derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into... (Review)
Review
Patient-derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice, have emerged as a pivotal approach in translational research, particularly in advancing precision medicine. As the first stage of PDX development, the patient-derived orthotopic xenograft (PDOX) models implant tumor tissue in mice in the corresponding anatomical locations of the patient. The PDOX models have several advantages, including high fidelity to the original tumor, heightened drug sensitivity, and an elevated rate of successful transplantation. However, the PDOX models present significant challenges, requiring advanced surgical techniques and resource-intensive imaging technologies, which limit its application. And then, the humanized mouse models, as well as the zebrafish models, were developed. Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay. The humanized mouse models are a hot topic in PDX model research. Regarding zebrafish patient-derived tumor xenografts (zPDX) and patient-derived organoids (PDO) as promising models for studying cancer and drug discovery, zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time. PDO models provide a cost-effective approach for drug testing that replicates the in vivo environment and preserves important tumor-related information for patients. The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.
Topics: Humans; Animals; Mice; Heterografts; Zebrafish; Xenograft Model Antitumor Assays; Prospective Studies; Neoplasms; Disease Models, Animal
PubMed: 37679891
DOI: 10.1002/ame2.12349 -
Animal Models and Experimental Medicine Feb 2023
Topics: Animals; Models, Animal; Biomedical Research
PubMed: 36762667
DOI: 10.1002/ame2.12307