{"title":"Breaking down the barriers to animal-free research.","authors":"Lauren Hope, Jarrod Bailey","doi":"10.1177/02611929251349465","DOIUrl":"https://doi.org/10.1177/02611929251349465","url":null,"abstract":"<p><p>For centuries, animals have been used in research due to their genetic and physiological similarities to humans. However, significant differences exist between humans and animals, which have the potential to confound results obtained from such experiments. These differences result in reduced translatability of animal data to humans, which is a major contributing factor to the 92% failure rate for novel therapies in clinical trials. Advances in scientific research have enabled the development of human-focused New Approach Methodologies (NAMs), which include <i>in silico</i> and 3-D <i>in vitro</i> models. By harnessing these novel approaches, greater predictive power for human biology, human diseases and assessment of novel therapies could be achieved. However, several obstacles remain to their wider adoption, including potential financial constraints, publication bias, and some concerns about the reliability of NAMs due to the novelty of this field, compared to animal studies. Here, we outline the differences between humans and animals used in research, discuss in detail the obstacles to the greater adoption of NAMs in research, and provide recommendations on how to accelerate a shift toward human-focused research.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"53 4","pages":"215-231"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela Zottis Chitolina, Thales Quedi Furian, Oscar Fernando Ortiz Granados, Karen Apellanis Borges, Thaína de Brites Weber, Izadora Bottega Gonçalves, Rafael Mollerke, Roberta de Castro Bohnmann, Tiele Maria Feijó de Fraga, Elisar Camilotti, Daniela Tonini da Rocha, Hamilton Luiz de Souza Moraes, Carlos Tadeu Pippi Salle
{"title":"Determining the pathogenicity of uropathogenic <i>Escherichia coli</i> strains in the <i>Galleria mellonella</i> larvae model.","authors":"Gabriela Zottis Chitolina, Thales Quedi Furian, Oscar Fernando Ortiz Granados, Karen Apellanis Borges, Thaína de Brites Weber, Izadora Bottega Gonçalves, Rafael Mollerke, Roberta de Castro Bohnmann, Tiele Maria Feijó de Fraga, Elisar Camilotti, Daniela Tonini da Rocha, Hamilton Luiz de Souza Moraes, Carlos Tadeu Pippi Salle","doi":"10.1177/02611929251349791","DOIUrl":"10.1177/02611929251349791","url":null,"abstract":"<p><p>Uropathogenic <i>Escherichia coli</i> (UPEC) is responsible for the majority of urinary tract infections, including those in catheterised patients. <i>Galleria mellonella</i>, an insect species, has been proposed as an alternative <i>in vivo</i> model to study the pathogenicity of <i>E. coli</i>. The aim of this study was to determine the pathogenicity of 48 UPEC strains using the larval disease score obtained from <i>G. mellonella</i> larvae model. The bacteria were also classified according to their phylogenetic group and the ability to form biofilms. The larvae were inoculated with the bacteria and observed for 72 hours. The LD<sub>50</sub>, mortality rate, and survival curve for each UPEC strain were assessed. A larval disease score (0-10) was determined, which considered mortality, larval activity, cocoon formation and melanisation. Phylogenetic groups were determined by using PCR, and biofilm formation was assessed by using the crystal violet assay. The larval disease score permitted the classification of the bacteria into three pathogenicity groups (low, intermediate and high). Bacteria were classified into six of the seven phylogenetic groups tested (i.e. A, B1, B2, C, D and F), but none were classified into group E. Biofilm-producing strains were detected at both incubation times used. There was no significant association between the larval disease score and the phylogenetic group. The larvae were susceptible to infection by all UPEC strains and the larval disease score deserves attention as a potential means of assessing the pathogenicity of UPEC isolates.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"203-214"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexya Azhakesan, Elena Seiz, Johann Kern, Laura Hendricks, Jens Fleckenstein, Frederic Jungbauer, Sonja Ludwig, Christoph Brochhausen, Luis Bugia, Claudia Scherl, Anne Lammert, Nicole Rotter, Annette Affolter
{"title":"Xeno-free alternatives to the use of fetal bovine serum in head and neck cancer explant culture.","authors":"Alexya Azhakesan, Elena Seiz, Johann Kern, Laura Hendricks, Jens Fleckenstein, Frederic Jungbauer, Sonja Ludwig, Christoph Brochhausen, Luis Bugia, Claudia Scherl, Anne Lammert, Nicole Rotter, Annette Affolter","doi":"10.1177/02611929251351559","DOIUrl":"10.1177/02611929251351559","url":null,"abstract":"<p><p>Patient-derived head and neck squamous cell carcinoma (HNSCC) explant models have been shown to retain the original tumour microenvironment and morphological characteristics. To enhance the human relevance of models and improve clinical outcomes, there is an emerging move toward preclinical models that are cultured in xeno-free media (i.e. media containing no non-human animal-derived components). Fetal bovine serum (FBS) has been the standard cell culture medium supplement in most <i>in vitro</i> systems. However, growing emphasis on ethical concerns, animal welfare considerations and reproducibility, as well as the need to implement the Three Rs principles, have driven substantial efforts to identify viable xeno-free alternatives to FBS. In this study, an <i>ex vivo</i> culture model for HNSCC was developed, based on the use of xeno-free media. Human platelet lysate (hPL)-supplemented medium and a commercially available xeno-free human mesenchymal stromal cell (MSC) expansion medium were evaluated, comparing HNSCC explant model growth to that in the 'standard' FBS-supplemented medium, over a 10-day culture period. To best reflect clinical conditions, the tissues were treated with radiochemotherapy (RCT) comprising cisplatin and fractionated irradiation. After 10 days, the tissues were formalin-fixed, paraffin-embedded, and assessed for the expression of key biomarkers, including PD-L1, Ki-67 and vimentin. The upregulation of PD-L1, as well as the downregulation of Ki-67 and vimentin, were consistent across all media, thus validating hPL-supplemented medium and MSC medium as viable alternatives to FBS-supplemented medium, for use in the culture of humanised HNSCC preclinical models.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"188-202"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Istanbul Workshop organised by the 'IMPROVE' COST Action Ethics Crossover Group.","authors":"Augusto Vitale, Simone Pollo, Nikos Kostomitsopoulos, Aurélie Thomas, Gamze Kaya, Kaan Bicici, Yesim Isil Ulman","doi":"10.1177/02611929251345074","DOIUrl":"https://doi.org/10.1177/02611929251345074","url":null,"abstract":"<p><p>The overall aim of the 'Improving the Quality of Biomedical Science with 3Rs Concepts' (IMPROVE) COST Action (CA21139) is to establish an interdisciplinary network dedicated to refining, harmonising and promoting the adoption of the Three Rs concepts, to enhance the quality of biomedical research. The 'IMPROVE' COST Action has assembled an Ethics Crossover Group composed of volunteer members from each of IMPROVE's four established Working Groups: 'Quality and translatability of science', 'Implementation', 'Dissemination' and 'Education'. This report relates to a two-day workshop, held in Acibadem University in Istanbul on 2-3 September 2024. The workshop was organised by the Ethics Crossover Group in line with the aims and the scope of the 'IMPROVE' COST Action, to address the ethical dimension of research and experiments on laboratory animals.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"53 4","pages":"232-235"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spotlight on Three Rs Progress.","authors":"","doi":"10.1177/02611929251350914","DOIUrl":"https://doi.org/10.1177/02611929251350914","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"53 4","pages":"181-183"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spotlight on Three Rs Progress.","authors":"","doi":"10.1177/02611929251334458","DOIUrl":"https://doi.org/10.1177/02611929251334458","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"53 3","pages":"125-126"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial.","authors":"Judith C Madden","doi":"10.1177/02611929251336678","DOIUrl":"https://doi.org/10.1177/02611929251336678","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"53 3","pages":"123-124"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}