Animal Models In Experimental Medicine

Cancer is a complex multifactorial disease that affects many people worldwide. Animal models play an important role in deciphering cancer biology and developing new therapies. The animal models widely used in cancer research include tumor xenografts, genetically engineered mice, chemically induced models, and spontaneous tumor models. These models provide a controlled environment to study cancer progression, the interaction of cancer and the immune system, and the effectiveness of new therapies. Although animal models have several advantages, it is important to identify their limitations and use them in conjunction with other preclinical models, such as in-vitro cell culture and patient-derived xenografts, to ensure that results are transferable to humans. In this chapter, we discuss the importance of animal models in cancer research, the different types of animal models, and their advantages and disadvantages. We also provide some examples of animal models used in cancer research. Collectively, animal models have been invaluable in advancing our understanding of cancer and will continue to be important tools in the development of new therapies.

Animal models have been, and continue to be, viable tools for investigating crucial scientific issues related to the pathogenesis of infectious diseases and serve as living platforms for testing novel therapeutics and/or vaccines. The use of animal models in studying infectious diseases is not only founded on the substantially shared biology of most mammals but also on the fact that many human infections are zoonotic, affecting a range of animal species. However, it is noticeable that the results retrieved from animal studies are not always reproducible in studies conducted on humans. The reliability of correlating data from animal models and translating them to human disease succeeds only in well-designed models where their relevance to the investigated human disease is well recognized. Preferable animal models respond similarly to the infectious agent as in humans, where the host’s interaction with the pathogen creates the same immunological and molecular environment. Several animal models have been designed to investigate the different aspects of the infectious process, such as biology, immunology, and pathogenesis. The murine model has been chosen for most studies investigating infectious diseases. Despite the limitations of the current animal models, remarkable progress has been achieved using these models, including a better understanding of host immune responses to infection, microbiome–pathogen interactions, the molecular mechanisms underlying tissue damage as well as validation of novel therapeutics and vaccine development.

Autoimmune diseases, known as immune-mediated diseases, occur when the immune system targets and attacks its own cells. In the field of medicine, there is a wide range of autoimmune conditions, including insulin-dependent Type 1 Diabetes Mellitus T1DM, Type 2 Diabetes Mellitus T2DM, Rheumatoid Arthritis RA, and Thyroiditis. These diseases can either be primary, with no clearly defined cause, or secondary, triggered by factors such as medications, infections, or malignancies. Animal models have proven invaluable for gaining insights into the underlying pathologies, causes, and specific signaling pathways associated with human autoimmune diseases. This is because these animal models share physiological similarities with humans and have shorter lifespans, allowing researchers to observe the entire disease progression. To replicate the complexity of autoimmune diseases in experimental models, researchers utilize various animal species, including monkeys, rabbits, rats, and mice. These methods can be broadly categorized into three strategies: immunization with autoantigens, transfer of autoimmunity, and induction through environmental factors. Numerous studies have been conducted using animal models to investigate the immunological pathophysiology of RA and assess the effectiveness of anti-rheumatic medications. There are several mouse models designed to mimic RAlike disease, each focusing on specific aspects of the condition. While animal models come with limitations, such as incomplete disease manifestations and limited genetic similarity to humans due to human genetic diversity, they remain an essential tool for understanding the pathogenesis of autoimmune diseases. Among the various animal models used in research, mice and other rodents like rats and hamsters account for over 90% of the total number of animals employed in these studies.

In ancient Greece, human anatomy and physiology models were first based on animals. More than 2,400 years ago, it was realized that studying animals could teach us a lot about ourselves. Animal models have been used in a wide range of medical research due to their similarity to humans. It is crucial that the selected animal model be as comparable to humans as possible. Because of how much their genetics, anatomy, and physiology match those of humans, animals are frequently used as study subjects for human diseases. Since they are the most popular mammal species utilized in tests, rats, mice, gerbils, guinea pigs, and hamsters have all been employed extensively in research. The use of animal models for various forms of anemia will be discussed in this chapter. The chapter will first discuss the use of animal models for inflammatory anemia, then for iron deficiency anemia in pregnant women, and finally for specific hereditary illnesses.

 “Ought we, for instance (to give an illustration of what I mean), to begin by discussing each separate species-man, lion, ox, and the like-taking each kind in hand independently of the rest, or ought we rather to deal first with the attributes which they have in common in virtue of some common element of their nature, and proceed from this as a basis for the consideration of them separately?”

-Aristotle (384 -322 BC), “On the Parts of Animals” 

As the number of Alzheimer's Disease (AD) cases continues to climb throughout the third decade of this century, researchers have yet to find a cure for the debilitating disease, even though the condition was first diagnosed in the early 1900s. Since then, scientists have elucidated its etiology, which shows that AD pathogenesis is a unique, complex amalgam of genetic, aging, comorbidities, and environmental factors for each patient. In no small part, animal models of AD have been instrumental in revealing disease pathways correlated to cognitive dysfunction and behavioral deficits; moreover, they have been indispensable as preclinical models for potential drug candidates. Both small and large mammalian models of AD will be surveyed and discussed, ranging from mice and rats to dogs, cats, sheep, pigs, and primates. Each of the model's advantages and disadvantages will be closely examined. 

Asthma is a significant heterogeneous disease with a high prevalence in children and adults. The main manifestations of asthma include wheezing, cough, dyspnea, chest tightness, mucus hypersecretion, and airway hyperresponsiveness to inhaled allergens with varying degrees of expiratory airflow limitation. Asthma is mainly considered as a state of dysregulated Th2 immune responses. However, clinical findings indicate that asthma is a heterogeneous disease with diverse phenotypes, endotypes and inflammatory cascades. Animal models are critical to advance insights into the pathophysiology underlying asthma development and to validate the safety and efficacy of novel therapeutics. Allergic asthma is mostly induced in murine models through sensitization of mice by one of the two main allergens: ovalbumin and house dust mite. Murine models were the most used model to investigate immune responses and genetic background of asthma as well as the basis of the heterogenous phenotypes/endotypes of the disease. Murine models have also been used to validate novel therapeutics. While murine models have offered a better understanding of certain pathways and reactants in the pathogenesis of asthma and airway remodeling, none of the current models entirely reflect the same features of human asthma. Therefore, great caution should be considered regarding the extrapolation of data derived from the murine asthma model to human asthma as they have many limitations and only partly reflect the pathology of human diseases.

This chapter on “Animal Models of Atherosclerosis” begins with the description of Atherosclerosis and the use of animal models. When lipids and fibrous tissue accumulate in the arterial wall, a condition known as atherosclerosis develops, which in turn causes the narrowing of the arteries and an increased likelihood of developing cardiovascular problems. Atherosclerosis animal models have been extensively utilized to investigate the disease's pathophysiology and evaluate potential treatments. This study's goal is to provide a brief overview of the analysis of the advantages and disadvantages of the most popular animal models of atherosclerosis, such as mice, rabbits, pigs, nonhuman primates, and dogs. Studies in animals mimicking atherosclerosis often use either high-fat diets or genetic manipulation to learn about the disease. A few of the characteristics of human disease, like lipid accumulation, vascular inflammation, and arterial remodeling, have been successfully reproduced in these models. However, the findings of animal research must be interpreted with caution due to species variations in atherosclerosis onset and progression. In sum, atherosclerosis animal models remain a vital resource for expanding our knowledge of the disease and discovering novel treatment approaches.

Food allergy can result in significant morbidity and mortality in adults and children. Animals are used to study and explore the pathological mechanisms of foodinduced sensitization and allergic reactions, and for experimenting with new modalities of treatment. Murine species became the preferred choice as a model of food allergy given the large accumulated work done in this field using the murine species leading to solid experience and development of valid experiential tools to characterize and assess immune mechanisms and reactions to food antigens. Other animals are used with varying success and have advantages and disadvantages such as rats, guinea pigs, dogs, pigs, and sheep. This chapter will describe these animal models highlighting their advantages and disadvantages and similarities to human immune systems.

Dentistry is a medical specialty that deals with teeth and gums, and animal models play an important part in its research and teaching. The use of animal models dates back centuries, and animals such as dogs, cats, rabbits, and horses have been utilized to investigate dental diseases and the anatomy and function of teeth. The selection criteria for animal models include their human-like physiology, the accessibility of relevant genetic resources, and usability and affordability. Animals are employed for research on various dental conditions, such as periodontal disease, dental caries, and oral cancer. Periodontitis is a dangerous gum infection that can lead to tooth loss, frequently brought on by a lack of oral hygiene. Dental caries are studied in animal models, and new preventative and therapeutic methods are explored. Oral cancer is studied, and its course and therapies are tested using animal models. The use of test methods specified by the International Organization for Standardization has helped to evaluate the biological reaction of various dental substances. Hamsters, which are usually correlated to mice, are employed to examine the features of periodontal and cariogenic diseases. Disease transmission can be studied in these animals as well. The dog periodontium is the one that most closely resembles that of humans. Canine periodontal disease is highly reflective of its human counterpart, and gingival recession is a hallmark of periodontitis in dogs, as it is in humans. Although animal models have been instrumental in the field of dentistry, there is not a single animal model that adequately replicates human soft and hard tissues, and it is crucial to choose an experimental model in light of the goals of the study.

Autism is a neurodevelopmental disorder that affects social communication and behavior. The etiology of this disorder is quite complex, involving genetic and environmental factors interacting to produce the condition. Animal models have been useful tools for investigating the underlying mechanisms of autism and have contributed significantly to our understanding of the disorder. This report is intended to review the various animal models of autism and the insights they have provided into the pathogenesis of autism.

Osteoporosis (OP) is a widespread disease characterized by reduced bone mass and disruption of bone microarchitecture. The association of this chronic metabolic condition with increased skeletal fragility and vulnerability to fracture is well-established. Although OP is both preventable and curable, being a clinically silent disease, it goes undetected until it manifests in the form of a fragility fracture. These fractures are associated with significant morbidity and mortality among patients. More than 200 million people worldwide are currently suffering from OP, making this critical disease a major public health concern. Due to ongoing demographic changes, the medical and socioeconomic impact of OP is predicted to increase further. However, to date, the management of OP remains a challenge, which necessitates the need for further research to fully understand its molecular mechanism and to establish novel prevention strategies and more effective treatment approaches. Animal models of OP are used widely as appropriate tools to enhance knowledge about disease etiology as well as to do pre-clinical evaluation of treatment and prevention strategies. This chapter aims to overview the currently available well-established animal models of OP with a focus on the ovariectomized rat model for postmenopausal OP. The information provided may help researchers to select an appropriate model in accordance with their research objective.

Autoimmune uveitis, a complex ocular inflammatory disorder, remains a significant challenge in ophthalmology and immunology research. This chapter delves into the intricate world of experimental models designed to mimic autoimmune uveitis in humans. We provide a comprehensive examination of these models, focusing on their utility, strengths, and limitations. First, we explore well-established experimental models, such as the classic rodent models induced by immunization with uveitogenic antigens, including interphotoreceptor retinoid-binding protein (IRBP) and retinal soluble antigen (S-Ag). These models have played a pivotal role in deciphering the immunopathogenic mechanisms underlying autoimmune uveitis. We discuss the methodologies employed to induce uveitis in these models and the histological and clinical correlates, shedding light on the similarities and differences with human disease. Furthermore, this chapter presents emerging experimental models, including genetically modified animals with targeted immune system alterations, such as knockout mice and transgenic models. These genetically engineered models allow researchers to dissect specific immune pathways involved in uveitis pathogenesis, offering a deeper understanding of the disease's immunological basis. In addition to animal models, we explore in vitro and ex vivo systems, such as organotypic retinal explants and co-culture systems, which enable the investigation of cell-cell interactions and the role of various immune cell populations within the ocular microenvironment. Throughout this chapter, we have discussed the critical insights gained from these models, including the identification of key immune cells, cytokines, and signaling pathways contributing to uveitis development. We also addressed the challenges and translational considerations when applying findings from experimental models to human autoimmune uveitis. Ultimately, this comprehensive analysis of experimental models for autoimmune uveitis research aims to provide researchers and clinicians with a valuable resource to enhance our understanding of the disease, facilitate the development of targeted therapies, and ultimately improve patient outcomes in the field of ocular immunology.