The ‘R’ principles in laboratory animal experiments

Lee, Kook Hyun; Lee, Jun Young; Kang, Byoung-Kab

doi:10.1186/s42826-020-00078-6

Cited by 44 publications

(39 citation statements)

References 8 publications

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“…Initially, the use of animal models enabled identifying the histopathological hallmarks of CIPN [61], but the need for a screening tool that is robust and reproducible highlights the necessity of simpler, faster, less expensive, and more relevant human models. This is also consistent with the principles of the 3Rs (Replacement, Reduction, and Refinement) in animal use in scientific research and testing [62].…”

Section: In Vitro Modelssupporting

confidence: 86%

Considerations for a Reliable In Vitro Model of Chemotherapy-Induced Peripheral Neuropathy

Eldridge

Scuteri

Jones

et al. 2021

Toxics

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Chemotherapy-induced peripheral neuropathy (CIPN) is widely recognized as a potentially severe toxicity that often leads to dose reduction or discontinuation of cancer treatment. Symptoms may persist despite discontinuation of chemotherapy and quality of life can be severely compromised. The clinical symptoms of CIPN, and the cellular and molecular targets involved in CIPN, are just as diverse as the wide variety of anticancer agents that cause peripheral neurotoxicity. There is an urgent need for extensive molecular and functional investigations aimed at understanding the mechanisms of CIPN. Furthermore, a reliable human cell culture system that recapitulates the diversity of neuronal modalities found in vivo and the pathophysiological changes that underlie CIPN would serve to advance the understanding of the pathogenesis of CIPN. The demonstration of experimental reproducibility in a human peripheral neuronal cell system will increase confidence that such an in vitro model is clinically useful, ultimately resulting in deeper exploration for the prevention and treatment of CIPN. Herein, we review current in vitro models with a focus on key characteristics and attributes desirable for an ideal human cell culture model relevant for CIPN investigations.

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Section: In Vitro Modelssupporting

confidence: 86%

Considerations for a Reliable In Vitro Model of Chemotherapy-Induced Peripheral Neuropathy

Eldridge

Scuteri

Jones

et al. 2021

Toxics

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“…This approach is highly flexible, straightforward and far less labor-intensive and expensive than previous approaches, (1) in which transgenic mice such as Lifeact-expressing strains were exploited to study actin dynamics during early differentiation in cultured hippocampal neurons ( Flynn et al, 2012 ) or (2) which required the breeding and scarification of a large number of knock-out mice and their control littermates. Hence, our replating protocol is very helpful to reduce the number of experimental animals, and it thereby complies with the 3R principle for a more ethical use of animals in biomedical research ( Russell and Burch, 1959 ; Lee et al, 2020b ). While we here used expression of fluorescent reporters and Cre/loxP-based gene inactivation for a proof of principle, genetic manipulation can be easily expanded to gene silencing via RNA interference or other modes of gene deletion, e.g., by exploiting the CRISPR/Cas system.…”

Section: Discussionmentioning

confidence: 94%

Neuron Replating, a Powerful and Versatile Approach to Study Early Aspects of Neuron Differentiation

Schneider

Duong

Rust

2021

eNeuro

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Neuron differentiation includes formation and outgrowth of neurites that differentiate into axons or dendrites. Directed neurite outgrowth is controlled by growth cones that protrude and retract actin-rich structures to sense environmental cues. These cues Significance statementUnraveling the molecular mechanisms that control neuron differentiation requires reporter gene expression or gene inactivation. In mouse primary hippocampal neurons, a widely used cellular system to study neuron differentiation, classical transfection methods are restricted to later stages of differentiation. Instead, electroporation allows genetic manipulation prior to seeding. However, time course of reporter gene expression or gene inactivation frequently hinders a full characterization of neuron differentiation, specifically of early stages. To circumvent this limitation, we combined electroporation-based genetic manipulation prior to initial seeding with a replating step after two days in vitro, which reset neurons into an undifferentiated stage. We show that replated neurons differentiated similar to nonreplated neurons. We provide a detailed protocol that allows to comprehensively characterize the molecular mechanisms underlying neuron differentiation.

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“…Only a few examples include improved experimental design and statistical analysis, new imaging methods, avoiding test repetitions to prove tested hypotheses, and data and resource sharing. ❖ Refinement [31]: Refers to reduced invasiveness, enhanced instrumentation, improved pain management that minimizes real or possible pain, discomfort, and distress [32][33][34]. For example, non-invasive strategies involve the use of adequate pain relief anesthetic and analgesic regimes.…”

Section: Alternatives To Animal Experimentsmentioning

confidence: 99%

Animals Used in Experimental Pharmacology and 3 Rs

Sivakrishnan¹,

Anbiah²

2021

Pharmacophore

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Drugs, vital weapons in healthcare, are only used in therapeutics after being tested in the lab. In both animals and humans, the roles of cells and organs are essentially the same. Many of the functions of animal cells are similar to those of human cells. Humans are classified as animals biologically. Animals are used to study how diseases impact living tissue, develop and test interventions, including animal medications, and educate future scientists and health-care practitioners. Animals have also played an important role in the advancement of research; several new drug discoveries have been made possible thanks to animal testing. Animal experimentation has its drawbacks, which include animal procurement, the complexity of conducting animal experiments, stringent rules, ethical considerations, and, more often than not, the interests of students. That is why, in today's world, other approaches and emerging technology, such as computer simulations, are increasingly replacing animal use. The article reveals animals used in experimental pharmacology. Alternatives for using animals in pharmacology education, on the other hand, have been suggested.

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The ‘R’ principles in laboratory animal experiments

Cited by 44 publications

References 8 publications

Considerations for a Reliable In Vitro Model of Chemotherapy-Induced Peripheral Neuropathy

Considerations for a Reliable In Vitro Model of Chemotherapy-Induced Peripheral Neuropathy

Neuron Replating, a Powerful and Versatile Approach to Study Early Aspects of Neuron Differentiation

Animals Used in Experimental Pharmacology and 3 Rs

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