scholarly journals Understanding Cellular Mechanisms Underlying Airway Epithelial Repair: Selecting the Most Appropriate Animal Models

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
B. Yahaya
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Animal Models ◽  
Model Systems ◽  
Large Animal ◽  
Airway Epithelial ◽  
Large Animal Models ◽  
Molecular Events ◽  
Epithelium Regeneration

Understanding the mechanisms underlying the process of regeneration and repair of airway epithelial structures demands close characterization of the associated cellular and molecular events. The choice of an animal model system to study these processes and the role of lung stem cells is debatable since ideally the chosen animal model should offer a valid comparison with the human lung. Species differences may include the complex three-dimensional lung structures, cellular composition of the lung airway as well as transcriptional control of the molecular events in response to airway epithelium regeneration, and repair following injury. In this paper, we discuss issues related to the study of the lung repair and regeneration including the role of putative stem cells in small- and large-animal models. At the end of this paper, the author discuss the potential for using sheep as a model which can help bridge the gap between small-animal model systems and humans.

THE IMPORTANCE OF LARGE ANIMAL MODELS FOR TRANSLATIONAL RESEARCH IN BONE TISSUE ENGINEERING

2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
S. J. Hollister ◽  
M. B. Wheeler ◽  
S. E. Feinberg ◽  
W. L. Murphy
Keyword(s):  
Tissue Engineering ◽  
Animal Model ◽  
Animal Models ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Large Animal ◽  
Engineering Studies ◽  
Large Animal Models ◽  
Clinical Indications ◽  
Human Situation

The translation of bone tissue engineering (BTE) research to clinical use has been absymal1. Outside of bone void filler biomaterials, only Bone Morphogenetic Protein 2 (BMP2) has made significant inroads to clinical practice, and even BMP2 use has been associated with significant complications including death, dysphagia, and ectopic bone formation. The dearth of BTE products can be attributed to two main causes: (1) the need to develop BTE systems, that successfully integrate scaffolds, growth factors like BMP2 and cells and (2) the need to adapt and implement such systems for a wide variety of clinical indications in CranioMaxilloFacial (CMF), Spine and Orthopedic Surgery. Of course, to fully develop BTE systems (Issue 1) and adapt them to realistic clinical indications, we must be able to test such systems in bone defects that are as close to the human situation as possible. Thus, the use of domestic large animals for bone tissue engineering is critical, as these animals provide challenges in both defect volume and functional loading that can mimic the human situation. In addition, FDA approval for BTE products either through a 510K or IDE/IND/PMA pathway requires the use of a large pre-clinical animal model. However, despite this need, only approximately 60 large animal bone tissue-engineering studies have been published in the past 10 years. Furthermore, NIH has funded only 8% of these studies, and of the 17 bone tissue engineering studies supported by NIH in 2010, only three utilized a large animal model, and none of these used an animal larger than a rabbit. Clearly, increased translation and regulatory approval of BTE therapies will require greater testing in large animal models. We will discuss the current dearth of relevant pre-clinical studies in BTE, and present our work addressing these issues by developing BTE systems (integrated scaffold, growth factor and stem-cell constructs) and testing these systems for realistic clinical applications using the Yorkshire and other swine species as a large pre-clinical animal model. We will detail our work in developing BTE systems for CMF reconstruction and spine fusion in the swine model. Reference Hollister S. J. and Murphy W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. B. (in press).

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 Stem Cells in Large Animal Models of Retinal and Neurological Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-2 ◽  
Author(s):  
Henry Klassen ◽  
Budd A. Tucker ◽  
Chee G. Liew ◽  
Morten La Cour ◽  
Heuy-Ching Wang
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Neurological Disease ◽  
Large Animal ◽  
Large Animal Models

scholarly journals Isolation, characterization and osteogenic differentiation of adipose-derived stem cells: from small to large animal models

2009 ◽  
Vol 338 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Elena Arrigoni ◽  
Silvia Lopa ◽  
Laura de Girolamo ◽  
Deborah Stanco ◽  
Anna T. Brini
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Osteogenic Differentiation ◽  
Large Animal ◽  
Adipose Derived Stem Cells ◽  
Large Animal Models

Animal Model Systems for the Study of Alcohol Teratology

2005 ◽  
Vol 230 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Timothy A. Cudd
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Basic Science ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Model System ◽  
Higher Order ◽  
Model Systems ◽  
Large Animal ◽  
Prenatal Alcohol

The incidence of fetal alcohol syndrome has not been declining even though alcohol has been established as a teratogen and significant efforts have been made to educate women not to abuse alcohol during pregnancy. In addition to further educational efforts, strategies to prevent or mitigate the damages of prenatal alcohol exposure are now under development. Animal models will play a significant role in the effort to develop these strategies. Because prenatal alcohol exposure causes damage by multiple mechanisms, depending on dose, pattern, and timing of exposure, and because no species of animal is the same as the human, the choice of which animal model to use is complicated. To choose the best animal model, it is necessary to consider the specific scientific question that is being addressed and which model system is best able to addressthe question. Animal models that are currently in use include nonhuman primates, rodents (rats, mice, guinea pigs), large animal models (pig and sheep), the chick, and simple animals, including fish, insects, and round worms. Each model system has strengths and weaknesses, depending on the question being addressed. Simple animal models are useful in exploring basic science questions that relate to molecular biology and genetics that cannot be explored in higher-order animals, whereas higher-order animal models are useful in studying complex behaviors and validating basic science findings in an animal that is more like the human. Substantial progress in this field will require the judicious use of multiple scientific approaches that use different animal model systems.

Understanding the role of stem cells in urinary bladder regeneration - a preclinical study in a large animal model

2017 ◽  
Vol 16 (3) ◽  
pp. e537 ◽  
Author(s):  
M. Pokrywczynska ◽  
A. Jundzill ◽  
M. Buhl ◽  
D. Balcerczyk ◽  
M. Rasmus ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Urinary Bladder ◽  
Preclinical Study ◽  
Large Animal Model ◽  
Large Animal ◽  
Bladder Regeneration

scholarly journals Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation

2021 ◽  
Vol 9 ◽  
Author(s):  
Piers Wilkinson ◽  
Ilya Y. Bozo ◽  
Thomas Braxton ◽  
Peter Just ◽  
Elena Jones ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
Bone Repair ◽  
Safety Data ◽  
Clinical Translation ◽  
Model Systems ◽  
Large Animal ◽  
Repair Gene ◽  
Public Health Burden ◽  
Large Animal Models

Bone defects and improper healing of fractures are an increasing public health burden, and there is an unmet clinical need in their successful repair. Gene therapy has been proposed as a possible approach to improve or augment bone healing with the potential to provide true functional regeneration. While large numbers of studies have been performed in vitro or in vivo in small animal models that support the use of gene therapy for bone repair, these systems do not recapitulate several key features of a critical or complex fracture environment. Larger animal models are therefore a key step on the path to clinical translation of the technology. Herein, the current state of orthopedic gene therapy research in preclinical large animal models was investigated based on performed large animal studies. A summary and an outlook regarding current clinical studies in this sector are provided. It was found that the results found in the current research literature were generally positive but highly methodologically inconsistent, rendering a comparison difficult. Additionally, factors vital for translation have not been thoroughly addressed in these model systems, and the risk of bias was high in all reviewed publications. These limitations directly impact clinical translation of gene therapeutic approaches due to lack of comparability, inability to demonstrate non-inferiority or equivalence compared with current clinical standards, and lack of safety data. This review therefore aims to provide a current overview of ongoing preclinical and clinical work, potential bottlenecks in preclinical studies and for translation, and recommendations to overcome these to enable future deployment of this promising technology to the clinical setting.

scholarly journals Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Damir Hamamdzic ◽  
Robert L. Wilensky
Keyword(s):  
Animal Models ◽  
Coronary Atherosclerosis ◽  
Pig Model ◽  
Large Animal ◽  
Rodent Models ◽  
Miniature Pig ◽  
Therapeutic Approaches ◽  
Large Animal Models ◽  
Atherosclerotic Lesions

Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

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