Animal models of arrhythmia: classic electrophysiology to genetically modified large animals

AbstractNeurodegenerative diseases represent a large group of neurological disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease. Although this group of diseases show heterogeneous clinical and pathological phenotypes, they share important pathological features characterized by the age-dependent and progressive degeneration of nerve cells that is caused by the accumulation of misfolded proteins. The association of genetic mutations with neurodegeneration diseases has enabled the establishment of various types of animal models that mimic genetic defects and have provided important insights into the pathogenesis. However, most of genetically modified rodent models lack the overt and selective neurodegeneration seen in the patient brains, making it difficult to use the small animal models to validate the effective treatment on neurodegeneration. Recent studies of pig and monkey models suggest that large animals can more faithfully recapitulate pathological features of neurodegenerative diseases. In this review, we discuss the important differences in animal models for modeling pathological features of neurodegenerative diseases, aiming to assist the use of animal models to better understand the pathogenesis and to develop effective therapeutic strategies.

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Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽

10.3390/cells10030713 ◽

2021 ◽

Vol 10 (3) ◽

pp. 713

Author(s):

Shu Fang ◽

Ditte Gry Ellman ◽

Ditte Caroline Andersen

Keyword(s):

Animal Models ◽

Vascular Grafts ◽

Small Diameter ◽

Large Animal ◽

Large Animal Models ◽

Graft Outcome ◽

Limited Success ◽

Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

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Large Animal Models of Vascularized Composite Allotransplantation: A Review of Immune Strategies to Improve Allograft Outcomes

Frontiers in Immunology ◽

10.3389/fimmu.2021.664577 ◽

2021 ◽

Vol 12 ◽

Author(s):

Abraham J. Matar ◽

Rebecca L. Crepeau ◽

Gerhard S. Mundinger ◽

Curtis L. Cetrulo ◽

Radbeh Torabi

Keyword(s):

Animal Models ◽

Ex Vivo ◽

Solid Organ Transplantation ◽

Tolerance Induction ◽

Large Animal ◽

Solid Organ ◽

Large Animal Models ◽

Large Animals ◽

And Function ◽

Made In

Over the past twenty years, significant technical strides have been made in the area of vascularized composite tissue allotransplantation (VCA). As in solid organ transplantation, the allogeneic immune response remains a significant barrier to long-term VCA survival and function. Strategies to overcome acute and chronic rejection, minimize immunosuppression and prolong VCA survival have important clinical implications. Historically, large animals have provided a valuable model for testing the clinical translatability of immune modulating approaches in transplantation, including tolerance induction, co-stimulation blockade, cellular therapies, and ex vivo perfusion. Recently, significant advancements have been made in these arenas utilizing large animal VCA models. In this comprehensive review, we highlight recent immune strategies undertaken to improve VCA outcomes with a focus on relevant preclinical large animal models.

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Nutritional Assessment of Genetically Modified Crops Using Animal Models

Genetically Modified Organisms in Food ◽

10.1016/b978-0-12-802259-7.00005-1 ◽

2016 ◽

pp. 39-50

Author(s):

R.D. Ekmay ◽

S. Papineni ◽

R.A. Herman

Keyword(s):

Animal Models ◽

Nutritional Assessment ◽

Genetically Modified ◽

Genetically Modified Crops

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ROLE OF ANIMAL MODELS IN PERIODONTAL RESEARCH - A REVIEW

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i7.25780 ◽

2018 ◽

Vol 11 (7) ◽

pp. 47

Author(s):

Sarah ` Banu ◽

Jaiganesh Ramamurthy

Keyword(s):

Animal Models ◽

Early Stage ◽

Periodontal Diseases ◽

Human Anatomy ◽

Anatomy And Physiology ◽

Advantages And Disadvantages ◽

Human Anatomy And Physiology ◽

Large Animals ◽

Periodontal Research

Periodontal diseases require treatment at an early stage to prevent further damage and aggravation of the disease. The most commonly seen periodontal diseases are gingivitis and periodontitis. Animals have contributed a major role in studying the different periodontal diseases and providing a proper treatment. Periodontal diseases are either induced in these experimental animal models or can be seen naturally. Different drugs are tested on the animals induced by the disease to find the most effective treatment for that particular disease. Different animals such as mice, rats, pigs, rabbits, hamsters, and rodents are used for the periodontal research. Different animals show a different reaction while some animals show no reaction. Each animal has its own advantages and disadvantages. The use of large animals brings a limitation in the due to its housing difficulties. Animals for periodontal research are chosen depending on their similarity with that of human anatomy and physiology. The use of these animals will help to replicate the disease seen in humans in a better and more accurate way. This will improve the treatment outcome and the prognosis of the disease. The drugs used can, hence, give a better idea about the effect it would have on the human body depending on the effects it shows on the animal models. Hence, the use of appropriate animals for the periodontal research is important to design a better treatment for these diseases. Hence, animal models play an important role in the periodontal research.

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Intratracheal aerosolization of viral vectors to newborn pig airways

BioTechniques ◽

10.2144/btn-2019-0150 ◽

2020 ◽

Vol 68 (5) ◽

pp. 235-239

Author(s):

Ashley L Cooney ◽

Patrick L Sinn

Keyword(s):

Gene Therapy ◽

Animal Models ◽

Endotracheal Tube ◽

Viral Vectors ◽

Small Animal ◽

Large Animal ◽

Large Animal Models ◽

Airway Diseases ◽

Efficient Delivery ◽

Large Animals

Gene therapy for airway diseases requires efficient delivery of nucleic acids to the airways. In small animal models, gene delivery reagents are commonly delivered as a bolus dose. However, large animal models are often more relevant for the transition from preclinical studies to human trials. Aerosolizing viral vectors to the lungs of large animals can maximize anatomical distribution. Here, we describe a technique for aerosolization of viral vectors to the airways of newborn pigs. Briefly, a pig is anesthetized and intubated with an endotracheal tube, and a microsprayer is passed through the endotracheal tube. A fine mist is then sprayed into the distal trachea. Widespread and uniform distribution of transgene expression is critical for developing successful lung gene therapy treatments.

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Bicuspid Aortic Valve in 2 Model Species and Review of the Literature

Veterinary Pathology ◽

10.1177/0300985819900018 ◽

2020 ◽

Vol 57 (2) ◽

pp. 321-331 ◽

Cited By ~ 1

Author(s):

Borja Fernández ◽

María Teresa Soto-Navarrete ◽

Alejandro López-García ◽

Miguel Ángel López-Unzu ◽

Ana Carmen Durán ◽

...

Keyword(s):

Animal Models ◽

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Wide Spectrum ◽

Genetically Modified ◽

Type A ◽

Mouse Strains ◽

Genetic Modifiers ◽

Interspecific Differences ◽

Congenital Cardiac Malformation

Bicuspid aortic valve (BAV) is the most common human congenital cardiac malformation. Although the etiology is unknown for most patients, formation of the 2 main BAV anatomic types (A and B) has been shown to rely on distinct morphogenetic mechanisms. Animal models of BAV include 2 spontaneous hamster strains and 27 genetically modified mouse strains. To assess the value of these models for extrapolation to humans, we examined the aortic valve anatomy of 4340 hamsters and 1823 mice from 8 and 7 unmodified strains, respectively. In addition, we reviewed the literature describing BAV in nonhuman mammals. The incidences of BAV types A and B were 2.3% and 0.03% in control hamsters and 0% and 0.3% in control mice, respectively. Hamsters from the spontaneous model had BAV type A only, whereas mice from 2 of 27 genetically modified strains had BAV type A, 23 of 27 had BAV type B, and 2 of 27 had both BAV types. In both species, BAV incidence was dependent on genetic background. Unlike mice, hamsters had a wide spectrum of aortic valve morphologies. We showed interspecific differences in the occurrence of BAV between humans, hamsters, and mice that should be considered when studying aortic valve disease using animal models. Our results suggest that genetic modifiers play a significant role in both the morphology and incidence of BAV. We propose that mutations causing anomalies in specific cardiac morphogenetic processes or cell lineages may lead to BAV types A, B, or both, depending on additional genetic, environmental, and epigenetic factors.

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