scholarly journals Genetically modified large animal models for investigating neurodegenerative diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weili Yang ◽  
Xiusheng Chen ◽  
Shihua Li ◽  
Xiao-Jiang Li
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Genetically Modified ◽  
Small Animal ◽  
Large Animal ◽  
Pathological Features ◽  
Large Animal Models ◽  
Progressive Degeneration ◽  
Large Animals ◽  
Lateral Sclerosis

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.

scholarly journals Intratracheal aerosolization of viral vectors to newborn pig airways

BioTechniques ◽  
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.

The Utility of Animal Models in the Preclinical Study of Interventions to Prevent Human Coronary Artery Restenosis: Analysis and Recommendations

1999 ◽  
Vol 81 (05) ◽  
pp. 835-843. ◽  
Author(s):  
T. R. Griggs ◽  
L. Badimon ◽  
G. J. Johnson
Keyword(s):  
Animal Models ◽  
Animal Studies ◽  
Small Animal ◽  
Preclinical Study ◽  
Large Animal ◽  
Human Coronary Artery ◽  
Large Animal Models ◽  
Luminal Narrowing ◽  
Small Animal Models ◽  
Large Animals

SummarySmall animal models have several advantageous characteristics, but those used in preclinical restenosis research have lacked efficacy in predicting the success of interventions to inhibit restenosis in humans.Large animal models have been more successful than small animal models in predicting efficacy of interventions to inhibit restenosis in humans, but the results of studies carried out with these models have not been uniformly predictive.Confirmation of the results of small animal studies in large animals has not always yielded information predictive of success in humans; however, the absence of such confirmation has had strong negative predictive value.Small animal models used for evaluation of interventions to inhibit luminal narrowing following arterial instrumentation have failed to closely simulate human atherosclerosis and the stenotic lesions subjected to instrumentation in humans.Transgenic, atherosclerotic animals hold promise for the development of more useful small animal models to study mechanisms of the response of diseased arteries to angioplasty and stents.The pig has been the most useful large animal to study stenosis/ restenosis, but more information is needed to overcome the limitations of this model.

Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

2017 ◽  
Vol 28 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Lan Huang ◽  
Fengyan Zhao ◽  
Yi Qu ◽  
Li Zhang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Large Animal ◽  
Large Animal Models ◽  
Neurological Research ◽  
Serious Disease ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

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

Cells ◽  
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.

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

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.

scholarly journals The Representative Porcine Model for Human Cardiovascular Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yoriyasu Suzuki ◽  
Alan C. Yeung ◽  
Fumiaki Ikeno
Keyword(s):  
Animal Models ◽  
Porcine Model ◽  
Small Animal ◽  
Large Animal ◽  
Murine Models ◽  
Practical Applications ◽  
Large Animal Models ◽  
Small Animal Models ◽  
Insight Into

To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions. This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.

scholarly journals A Review of the Current Mammalian Models of Alzheimer’s Disease and Challenges That Need to Be Overcome

2021 ◽  
Vol 22 (23) ◽  
pp. 13168
Author(s):  
Natasha Elizabeth Mckean ◽  
Renee Robyn Handley ◽  
Russell Grant Snell
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Mouse Model ◽  
Mouse Models ◽  
Small Animal ◽  
Large Animal ◽  
Complex Disorders ◽  
Large Animal Models ◽  
The Impact

Alzheimer’s disease (AD) is one of the looming health crises of the near future. Increasing lifespans and better medical treatment for other conditions mean that the prevalence of this disease is expected to triple by 2050. The impact of AD includes both the large toll on individuals and their families as well as a large financial cost to society. So far, we have no way to prevent, slow, or cure the disease. Current medications can only alleviate some of the symptoms temporarily. Many animal models of AD have been created, with the first transgenic mouse model in 1995. Mouse models have been beset by challenges, and no mouse model fully captures the symptomatology of AD without multiple genetic mutations and/or transgenes, some of which have never been implicated in human AD. Over 25 years later, many mouse models have been given an AD-like disease and then ‘cured’ in the lab, only for the treatments to fail in clinical trials. This review argues that small animal models are insufficient for modelling complex disorders such as AD. In order to find effective treatments for AD, we need to create large animal models with brains and lifespan that are closer to humans, and underlying genetics that already predispose them to AD-like phenotypes.

Premature guinea pigs: a new paradigm to investigate the late-effects of preterm birth

2014 ◽  
Vol 6 (2) ◽  
pp. 143-148 ◽  
Author(s):  
M. Berry ◽  
C. Gray ◽  
K. Wright ◽  
R. Dyson ◽  
I. Wright
Keyword(s):  
Preterm Birth ◽  
Animal Models ◽  
Guinea Pigs ◽  
Small Animal ◽  
Large Animal ◽  
New Paradigm ◽  
Short Term ◽  
Human Infants ◽  
Caesarean Birth ◽  
Large Animal Models

Preterm birth is common and the associated short-term morbidity well described. The adult-onset consequences of preterm birth are less clear, but cardiovascular and metabolic health may be adversely affected. Although large animal models of preterm birth addressing important short-term issues exist, long-term studies are hampered by significant logistical constraints. Current small animal models of prematurity require terminal caesarean section of the mother; both caesarean birth and early maternal care modify offspring adult cardio-metabolic function.We describe a novel method for inducing preterm labour in guinea pigs. With support comparable to that received by moderately preterm human infants, preterm pups are viable. Growth trajectories between preterm and term-born pups differ significantly; between term equivalent age and weaning ex-preterm animals demonstrate increased weight and ponderal index.We believe this novel paradigm will significantly improve our ability to investigate the cardio-metabolic sequelae of preterm birth throughout the life course and into the second generation.

scholarly journals Large animals in neurointerventional research: A systematic review on models, techniques and their application in endovascular procedures for stroke, aneurysms and vascular malformations

2019 ◽  
Vol 39 (3) ◽  
pp. 375-394 ◽  
Author(s):  
Andrea M Herrmann ◽  
Stephan Meckel ◽  
Matthew J Gounis ◽  
Leona Kringe ◽  
Edith Motschall ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Animal Models ◽  
Translational Research ◽  
Arteriovenous Malformations ◽  
Vascular Malformations ◽  
Large Animal ◽  
Large Animal Models ◽  
Large Animals ◽  
Study Designs

Neuroendovascular procedures have led to breakthroughs in the treatment of ischemic stroke, intracranial aneurysms, and intracranial arteriovenous malformations. Due to these substantial successes, there is continuous development of novel and refined therapeutic approaches. Large animal models feature various conceptual advantages in translational research, which makes them appealing for the development of novel endovascular treatments. However, the availability and role of large animal models have not been systematically described so far. Based on comprehensive research in two databases, this systematic review describes current large animal models in neuroendovascular research including their primary use. It may therefore serve as a compact compendium for researchers entering the field or looking for opportunities to refine study concepts. It also describes particular applications for ischemic stroke and aneurysm therapy, as well as for the treatment of arteriovenous malformations. It focuses on most promising study designs and readout parameters, as well as on important pitfalls in endovascular translational research including ways to circumvent them.

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