Aligning with the 3Rs: alternative models for research into muscle development and inherited myopathies.

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES BMC Veterinary Research Pub Date : 2024-10-18 DOI:10.1186/s12917-024-04309-z
Hashir Mehmood, Paul R Kasher, Richard Barrett-Jolley, Gemma L Walmsley
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Abstract

Inherited and acquired muscle diseases are an important cause of morbidity and mortality in human medical and veterinary patients. Researchers use models to study skeletal muscle development and pathology, improve our understanding of disease pathogenesis and explore new treatment options. Experiments on laboratory animals, including murine and canine models, have led to huge advances in congenital myopathy and muscular dystrophy research that have translated into clinical treatment trials in human patients with these debilitating and often fatal conditions. Whilst animal experimentation has enabled many significant and impactful discoveries that otherwise may not have been possible, we have an ethical and moral, and in many countries also a legal, obligation to consider alternatives. This review discusses the models available as alternatives to mammals for muscle development, biology and disease research with a focus on inherited myopathies. Cell culture models can be used to replace animals for some applications: traditional monolayer cultures (for example, using the immortalised C2C12 cell line) are accessible, tractable and inexpensive but developmentally limited to immature myotube stages; more recently, developments in tissue engineering have led to three-dimensional cultures with improved differentiation capabilities. Advances in computer modelling and an improved understanding of pathogenetic mechanisms are likely to herald new models and opportunities for replacement. Where this is not possible, a 3Rs approach advocates partial replacement with the use of less sentient animals (including invertebrates (such as worms Caenorhabditis elegans and fruit flies Drosophila melanogaster) and embryonic stages of small vertebrates such as the zebrafish Danio rerio) alongside refinement of experimental design and improved research practices to reduce the numbers of animals used and the severity of their experience. An understanding of the advantages and disadvantages of potential models is essential for researchers to determine which can best facilitate answering a specific scientific question. Applying 3Rs principles to research not only improves animal welfare but generates high-quality, reproducible and reliable data with translational relevance to human and animal patients.

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符合 3R:肌肉发育和遗传性肌病研究的替代模式。
遗传性和获得性肌肉疾病是人类医学和兽医学患者发病和死亡的重要原因。研究人员利用模型来研究骨骼肌的发育和病理,提高我们对疾病发病机制的认识,并探索新的治疗方案。在实验动物(包括鼠类和犬类模型)上进行的实验使先天性肌病和肌肉萎缩症的研究取得了巨大进步,这些研究成果已转化为对人类患者的临床治疗试验。虽然动物实验促成了许多重大而有影响的发现,否则这些发现可能无法实现,但我们有伦理道德义务,在许多国家还有法律义务考虑替代方法。本综述讨论了可替代哺乳动物进行肌肉发育、生物学和疾病研究的模型,重点是遗传性肌病。在某些应用中,细胞培养模型可用于替代动物:传统的单层培养(例如,使用永生化的 C2C12 细胞系)容易获得、易于操作且成本低廉,但在发育上仅限于未成熟的肌管阶段;最近,组织工程学的发展带来了分化能力更强的三维培养。计算机建模的进步和对病理机制认识的提高很可能预示着新的模型和替代机会。如果不可能实现,3Rs 方法主张部分替代,即使用智商较低的动物(包括无脊椎动物(如秀丽隐杆线虫和果蝇)和小型脊椎动物(如斑马鱼)的胚胎阶段),同时改进实验设计和研究方法,以减少使用动物的数量和动物经历的严重程度。了解潜在模型的优缺点对于研究人员确定哪种模型最有利于回答特定的科学问题至关重要。将 3Rs 原则应用于研究,不仅能改善动物福利,还能产生高质量、可重复和可靠的数据,对人类和动物患者具有转化意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Veterinary Research
BMC Veterinary Research VETERINARY SCIENCES-
CiteScore
4.80
自引率
3.80%
发文量
420
审稿时长
3-6 weeks
期刊介绍: BMC Veterinary Research is an open access, peer-reviewed journal that considers articles on all aspects of veterinary science and medicine, including the epidemiology, diagnosis, prevention and treatment of medical conditions of domestic, companion, farm and wild animals, as well as the biomedical processes that underlie their health.
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