THE USE OF RUMINANTS FOR BIOMEDICAL RESEARCH IN PERINATALOGY

2012 ◽  
Vol 24 (1) ◽  
pp. 286
Author(s):  
Pascale Chavatte-Palmer ◽  
Anne Tarrade ◽  
Vassilis Tsatsaris ◽  
Olivier Morel

As a consequence of obvious ethical considerations concerning what is feasible or not in the field of human biomedical research, animal models are of critical importance both for human and veterinary medicine and cognitive scientists. Many species have been and are currently used as animal models. Rodents and lagomorphs are the most popular, essentially because of their low cost, handling and rearing facilities, limited ethical impact, and the availability of a wide range of genetic research tools in these species. Nevertheless, these models present some limitations. The physiological mechanisms observed in these species might be far from those of humans. For example, due to the large number of embryos and short gestation length, rodents and lagomorphs are not very suitable in several fields of perinatal research. Large animal species are required when surgical approaches or new medical devices have to be evaluated. The pig is widely used in these situations, as well as ruminants such as the sheep and the goat. Concerning physiological, anatomical and genetic considerations, large primates could be considered as the “gold standard” animal model because of their important similarities with humans. However, their use for biomedical research is greatly limited by their behavioral and social organization, raising important ethical questions, and their elevated cost. A very large number of experiments using ruminants as animal models have been published. A rapid bibliometric analysis performed using the Pubmed database from 1969 to 2010 retrieved 1108 literature reviews using the Mesh keywords “ruminant & animal model”. Six hundred and twelve references were available only for the year 2009 using the same Mesh research and covering all types of publications. The sheep is the most widely used ruminant model, and no less than 5393 publications can be found using the Mesh keywords “sheep & animal model”. The current presentation will focus on the most outstanding examples of great biomedical advances carried out with ruminant as models in the field of perinatal research. In this paper, the pivotal role of ruminants in the evaluation and development of new pharmacological treatments, new invasive procedures in fetuses, gestational imaging and genetic approaches will be developed, with their clinical context, including our own work on feto-placental imaging and the assessment of placental blood flow using quantitative 3D Doppler.

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.


2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
S. J. Hollister ◽  
M. B. Wheeler ◽  
S. E. Feinberg ◽  
W. L. Murphy

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).


Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 140 ◽  
Author(s):  
Steven Erwood ◽  
Bin Gu

Endonuclease-mediated genome editing technologies, most notably CRISPR/Cas9, have revolutionized animal genetics by allowing for precise genome editing directly through embryo manipulations. As endonuclease-mediated model generation became commonplace, large fragment knock-in remained one of the most challenging types of genetic modification. Due to their unique value in biological and biomedical research, however, a diverse range of technological innovations have been developed to achieve efficient large fragment knock-in in mammalian animal model generation, with a particular focus on mice. Here, we first discuss some examples that illustrate the importance of large fragment knock-in animal models and then detail a subset of the recent technological advancements that have allowed for efficient large fragment knock-in. Finally, we envision the future development of even larger fragment knock-ins performed in even larger animal models, the next step in expanding the potential of large fragment knock-in in animal models.


Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker

The Mouse Grimace Scale (MGS) was developed 10 years ago to assess pain through characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. A comprehensive scoping review of the academic literature was performed. The MGS has been employed mainly in evaluation of acute pain, particularly in the pain and neuroscience research fields. There has however been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method does allow detection of pain of a longer duration, up to a month post-initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.


Author(s):  
Alexandra N Witt ◽  
Rachel D Green ◽  
Andrew N Winterborn

Animal models are at the forefront of biomedical research for studies of viral transmission, vaccines, and pathogenesis, yetthe need for an ideal large animal model for COVID-19 remains. We used a meta-analysis to evaluate published data relevantto this need. Our literature survey contained 22 studies with data relevant to the incidence of common COVID-19 symptomsin rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), African green monkeys (Chlorocebusaethiops), and ferrets (Mustela putorius furo). Rhesus macaques had leukocytosis on Day 1 after inoculation and pneumonia on Days 7 and 14 after inoculation, in frequencies that were similar enough to humans to reject the null hypothesis of a Fisher exact test. However, the differences in overall presentation of disease were too different from that of humans to successfully identify any of these 4 species as an ideal large animal of COVID-19. The greatest limitation to the current study is a lack of standardization in experimentation and reporting. To expand our understanding of the pathology of COVID-19 and evaluate vaccine immunogenicity, we must extend the unprecedented collaboration that has arisen in the study of COVID-19 to include standardization of animal-based research in an effort to find the optimal animal model.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
B. Yahaya

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.


2005 ◽  
Vol 230 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Timothy A. Cudd

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.


2014 ◽  
Vol 6 (6) ◽  
pp. 531-538 ◽  
Author(s):  
Aaron R. L. Dawes ◽  
Peter H. Seidenberg

Context: Sports-related injuries of the hip are a common complaint of both competitive and recreational athletes of all ages. The anatomic and biomechanical complexity of the hip region often cause diagnostic uncertainty for the clinicians evaluating these injuries. Therefore, obtaining additional diagnostic information is often crucial for providing injured athletes with a prompt and accurate diagnosis so they can return to activity as soon as possible. Musculoskeletal ultrasound is becoming increasingly important in evaluating and treating sports-related injuries of the hip. Evidence Acquisition: The PubMed database was searched in May of 2013 for English-language articles pertaining to sonography of sports injuries of the hip using the following keywords in various combinations: musculoskeletal, ultrasound, hip, hip sonography, and sports. Study Design: Clinical review. Level of Evidence: Level 4. Results: Musculoskeletal ultrasound is currently being used for both diagnosis and treatment in a wide range of acute and chronic conditions affecting the hip, including tendinosis, tendon/muscle strains, ligamentous sprains, enthesopathies, growth plate injuries, fractures, bursitis, effusions, synovitis, labral tears, and snapping hip. Therapeutically, it is used to guide injections, aspirations, and biopsies. Conclusion: Musculoskeletal ultrasound use is expanding and will likely continue to do so as more clinicians realize its capabilities. Characteristics, including accessibility, portability, noninvasiveness, dynamic examination, power Doppler examination, and low cost highlight the potential of ultrasound.


2017 ◽  
pp. 899-915 ◽  
Author(s):  
N. PATELIS ◽  
D. MORIS ◽  
D. SCHIZAS ◽  
C. DAMASKOS ◽  
D. PERREA ◽  
...  

Abdominal aortic aneurysm (AAA) is a prevalent and potentially life threatening disease. Many animal models have been developed to simulate the natural history of the disease or test preclinical endovascular devices and surgical procedures. The aim of this review is to describe different methods of AAA induction in animal models and report on the effectiveness of the methods described in inducing an analogue of a human AAA. The PubMed database was searched for publications with titles containing the following terms “animal” or ‘‘animal model(s)’’ and keywords “research”, “aneurysm(s)’’, “aorta”, “pancreatic elastase’’, “Angiotensin”, “AngII” “calcium chloride” or “CaCl2”. Starting date for this search was set to 2004, since previously bibliography was already covered by the review of Daugherty and Cassis (2004). We focused on animal studies that reported a model of aneurysm development and progression. A number of different approaches of AAA induction in animal models has been developed, used and combined since the first report in the 1960’s. Although specific methods are successful in AAA induction in animal models, it is necessary that these methods and their respective results are in line with the pathophysiology and the mechanisms involved in human AAA development. A researcher should know the advantages/disadvantages of each animal model and choose the appropriate model.


2017 ◽  
Vol 01 (02) ◽  
pp. 074-082
Author(s):  
Jordan Newson ◽  
Nickolas Kinachtchouk ◽  
Kyle Schachtschneider ◽  
Regina Schwind ◽  
Lawrence Schook

AbstractAdvances in biomedical research require animal models that accurately recapitulate human disease. Without such models, progress against human diseases such as cancer is significantly hindered. Here, we present the current landscape on available and emerging hepatocellular carcinoma (HCC) animal models. HCC is the second leading cause of cancer death worldwide, with an annual death toll exceeding 745,000. Stunningly, only 15% of HCC patients are candidates for curative therapy, leading 85% of patients to seek palliative therapeutic options. The VX2 rabbit model is considered the most relevant and widely used HCC model; however, more reliable HCC models are critically needed. In general, animal models for biomedical research should (1) mimic the human disease on a molecular basis, (2) derive from a relevant cell line that lends itself to in vitro study, (3) be reliable and predictable, (4) manifest survival differences, (5) allow for accurate treatment assessment, (6) be readily imaged, and (7) occur in similar background settings as the human disease. Over the past decades, numerous small animal models have been utilized for HCC studies; however, the development of new large animal models as qualified alternatives to murine models represents a key technology to advance research into human clinical trials.


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