Alternatives to animal experimentation for hormonal compounds research

Abstract

Alternatives to animal testing and the identification of reliable methods that may decrease the need for animals are currently the subject of intense investigation worldwide. Alternative testing procedures are particularly important for synthetic and natural chemicals that exert their biological actions through binding nuclear receptors, called nuclear receptors-interacting compounds (NR-ICs), for which research is increasingly emphasizing the limits of several models in the accurate estimation of the physiological consequences of exposure to these compounds. In particular, estrogen receptor interacting compounds (ER-ICs) have a great impact on human health from the therapeutic, nutritional, and toxicological point of view due to the highly permissive nature of the estrogen receptors towards a large number of natural and synthetic compounds. Similar to in vitro systems, recently generated animal models (e.g., animal models generated for the study of estrogen receptor ligands) may fulfill the 3R principles: refine, reduce, and replace. If used correctly, NR-regulated models, such as reporter mice, xenopus, or zebrafish, and models obtained by somatic gene transfer in reporter systems, combined with imaging technologies, may contribute to strongly decreasing the overall number of animals required for NR-IC testing and research. With these models, flexible and highly standardized parameters and reporter marker quantification can be obtained. Here, we highlight the need for the substitution of currently used testing models with more appropriate ones that can reproduce the features and reactivity of specific mammalian target tissue/organs. We consider the promotion of this advancement a research priority bearing scientific, economic, social, and ethical relevance.

RETRACTED: Vascularised human tissue models: A new approach for the refinement of biomedical research

“…The new technologies established in the field of tissue engineering represent a useful, biologically driven approach, to establish long-time functional tissues as models for risk assessment of substances by reflecting underlying physiological mechanisms in the human body (Penza et al, 2009;Vitale et al, 2009).…”

“…Artificial two-dimensional cell culture conditions do not address their spatial organization, resulting in distorted cellular functions. For example, polarized cells of the parenchymal tissue, which normally require complex cellular interactions, may not behave physiologically when adhering to solid substrates, as in the case of conventional culture conditions (Penza et al, 2009).…”

Upcyte®Microvascular Endothelial Cells Repopulate Decellularized Scaffold

“…51,52 The new technologies established in material research and the cell-culture technique has led to the development of longtime bioartificial tissues that can be used as models for experimental setups reflecting underlying physiological mechanisms in the human body. 53,54 The supply of nutrients to the construct is important to keep the grafts viable. Tissues sections that are approximately 200 mm thick can be supplied by diffusion alone.…”

Ethical Issues Associated with the Use of Animal Experimentation in Behavioral Neuroscience Research

“…Although, the search for animal-free methods is complex in any research field (Doktorova et al 2012;Hendriksen 2009;Huggins 2003;Manciocco et al 2009;Penza et al 2009), in Behavioral Neuroscience in particular, the modeling of complex systems such as executive processes of the brain or the central nervous system (CNS) may indeed limit the possibility of finding alternatives and may thus demand use of animal models; at least at present, available in vitro methods, and computer models seem unable to display the complexity of CNS-generated, behavioral-cognitive processes. It may be of note, however, that the declared goal of one of the current EU flagship programs (the Human Brain Project) is: "to build a completely new ICT infrastructure for neuroscience, and for brain-related research in medicine and computing, catalyzing a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities."…”