Necessity, Use, and Care of Laboratory Dogs at the U.S. Department of Veterans Affairs (2020) / Chapter Skim
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4 Alternatives to the Use of Laboratory Dogs
4 Alternatives to the Use of Laboratory Dogs
Pages 89-120
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From page 89... ...
Four broad categories of alternatives are considered in this chapter. The first is companion dogs volunteered by their owners for clinical trials.
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As discussed in Chapter 3, companion dogs may also offer certain scientific advantages over highly controlled studies using laboratory dogs. For example, while laboratory animals are generally chosen for their homogeneity, companion dogs display both (well-characterized)
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From page 91... ...
If a dog with a high spinal injury suffered respiratory paralysis or severe compromise, sustaining it through prolonged ventilator support would not be consistent with humane and ethical practice; this also applies to the long-term study of cervical SCI in laboratory animals. Therefore, companion dogs can be useful for studying SCI and its response to treatment but not for research on quadriplegia or long-term respiratory support.
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From page 92... ...
. Optimization of VA Research to Use Companion Dogs The VA has an opportunity to become a premier biomedical research entity engaging formally with veterinary expertise, both to enhance the experience of laboratory dogs and to conduct clinical trials in companion dogs, using companion dog studies to replace laboratory dog research wherever possible.
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From page 93... ...
2. Collaborating with researchers conducting clinical trials in companion dogs to identify or develop trials to benefit veterans.
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From page 94... ...
Department of Veterans Affairs likely to benefit from development of a companion dog model include chronic pain, diabetes, cardiovascular disease, and senile dementia, including Alzheimer's disease. The utility of companion dogs may increase if other biomedical research areas wherein their use is scientifically valid could be identified and if there is an infrastructure in place to facilitate the conduct of studies that use companion dogs.
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In contrast, animal models have enabled the direct study of the progression of the disease (Daugherty et al., 2017)
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NZWRs fed a high-fat/high-cholesterol diet are the most commonly used rabbit model in atherosclerosis. In certain genetic models or with the use of mechanical manipulations, lesions will form in coronary arteries (Fan and Watanabe, 2000; Shiomi et al., 2003; van der Heiden et al., 2016)
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. Various laboratory animal models have been employed, and one human trial is recruiting participants as of the writing of this report (NLM, 2019)
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One example is the transplantation of Schwann cells to facilitate spinal cord regeneration, which was shown to be successful first in rodents and then in pigs (Santamaria et al., 2018) , prior to the initiation of human clinical trials.
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From page 99... ...
. Pigs In general, cancer cell biology in pigs and dogs is more analogous to that in humans than are small animal models, while the larger animals' size and anatomy make them well-suited for interventional studies, including device testing and surgical practice (Flisikowska et al., 2013; Gardner et al., 2016)
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. Diabetes While laboratory dogs are no longer used in large numbers to study diabetes (and published research is more likely to use companion dogs with naturally acquired disease)
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. Despite the variety of approaches currently available for studying SCI, there is no laboratory animal model that mimics the diversity of injuries and the diversity of the human population.
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From page 102... ...
Conclusion 4-3: With respect to other animal models, rats and mice are the predominant species used for biomedical research in the fields of cardiovascular disease, spinal cord injury, cancer, and diabetes. For studies that cannot be performed in rodents (due to constraints of size, anatomy, or physiology)
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Stem Cells Human pluripotent stem cell–derived cardiomyocytes have revolutionized the field of cardiovascular research. Methods for differentiating human induced pluripotent stem cells (hiPSCs)
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Human Heart Tissue Although laboratory animals provide a convenient and consistent medium for research into mammalian biology, the historical difficulty of translating these findings into (human) clinical practice is well documented and universally acknowledged.
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, bringing researchers another important step closer to recapitulating the complexity of the in situ human heart. Spinal Cord Injury Bioprinting The complexity of the central nervous system presents a significant challenge to the construction of non-animal systems for studying SCI.
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From page 106... ...
. In comparing organ chips to animal models, it is worth noting that as cancer treatment becomes increasingly specific -- for example, with the use of therapeutic monoclonal antibodies -- the ability to evaluate therapies in non-human species becomes more challenging (Sontheimer-Phelps et al.,
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From page 107... ...
NIH is contributing to this effort on several fronts, including NCI's Cancer Tissue Engineering Collaborative Research Program as well as a grant instrument supporting research to test the utility of incorporating "tissue chip" models into clinical trial design (HHS, 2019; NCI, 2019)
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From page 108... ...
. Even in the case of protocols that still require the use of laboratory animals, researchers need to be encouraged to evaluate and incorporate NAMs where feasible.
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This framework should prioritize: • Modifying the protocol review processes (see Recommendation 3) to require and support robust consideration of NAMs, human clinical trials, companion dogs, and alternative animal models.
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This effort should result in the following: • Increased collaborations with external scientists and use of public–private partnerships to promote cross-sector communication and cooperation. • The fostering of collaborations with researchers conducting clinical trials in companion dogs to identify or develop trials to benefit veterans and dogs.
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From page 111... ...
2017. Veterinary clinical trials are on trial.
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2016. First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes -- Chapter 5: Recipient monitoring and response plan for preventing disease transmission.
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2016. A systematic review of adverse event reporting in companion animal clinical trials evaluating cancer treatment.
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2018. Animal models of obesity and diabetes mellitus.
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2017. Animal models of atherosclerosis.
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2017. Human in silico drug trials demonstrate higher accuracy than animal models in predicting clinical pro-arrhythmic cardiotoxicity.
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2008. Animal models and the prediction of efficacy in clinical trials of analgesic drugs: A critical appraisal and call for uniform reporting standards.
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2016. First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes -- Chapter 2a: Source pigs -- Preventing xenozoonoses.
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2016. Animal models for plaque rupture: A biomechanical assessment.
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