Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Second International Conference on 3Rs Research and Progress,Hyderabad,2021
Restricted accessResearch articleFirst published online March, 2022
Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Second International Conference on 3Rs Research and Progress,Hyderabad,2021
The fact that animal models fail to replicate human disease faithfully is now being widely accepted by researchers across the globe. As a result, they are exploring the use of alternatives to animal models. The time has come to refine our experimental practices, reduce the numbers and eventually replace the animals used in research with human-derived and human-relevant 3-D disease models. Oncoseek Bio-Acasta Health, which is an innovative biotechnology start-up company based in Hyderabad and Vishakhapatnam, India, organises an annual International Conference on 3Rs Research and Progress. In 2021, this conference was on ‘Advances in Research Animal Models and Cutting-Edge Research in Alternatives’. This annual conference is a platform that brings together eminent scientists and researchers from various parts of the world, to share recent advances from their research in the field of alternatives to animals including new approach methodologies, and to promote practices to help refine animal experiments where alternatives are not available. This report presents the proceedings of the conference, which was held in hybrid mode (i.e. virtual and in-person) in November 2021.
MeigsL. Animal testing and its alternatives — the most important omics is economics. ALTEX2018; 35: 275–305.
2.
WeinhartMHockeAHippenstielS, et al.3D organ models — Revolution in pharmacological research?Pharmacol Res2019; 139: 446–451.
3.
KnightEPrzyborskiS. Advances in 3D cell culture technologies enabling tissue-like structures to be created in vitro. J Anat2014; 227: 746–756.
4.
ShigetaSLuiGYLShawR, et al.Targeting BET proteins BRD2 and BRD3 in combination with PI3K-AKT inhibition as a therapeutic strategy for ovarian clear cell carcinoma. Mol Cancer Ther2021; 20: 691–703.
5.
GayanSTeliADeyT. Inherent aggressive character of invasive and non-invasive cells dictates the in vitro migration pattern of multicellular spheroid. Sci Rep2017; 7: 11527.
6.
GayanSTeliANairA, et al.Macro- and micro-nutrient-based multiplex stress conditions modulate in vitro tumorigenesis and aggressive behavior of breast cancer spheroids. In Vitro Models2021; 1: 85–101.
7.
CloughHCO'BrienMZhuX, et al.Neutrally charged self-assembling peptide hydrogel recapitulates in vitro mechanisms of breast cancer progression. Mater Sci Eng C Mater Biol Appl2021; 127: 112200.
8.
LachowskiDMatellanCCortesE, et al.Self-assembling polypeptide hydrogels as a platform to recapitulate the tumor microenvironment. Cancers (Basel)2021; 13: 3286.
9.
GopiKSubramanianIKrantiM, et al.Preparation of ingestible antibodies to neutralize the binding of SarsCoV2 RBD (receptor binding domain) to human ACE2 receptor. bioRxiv2021; 10.19.464951.
10.
ShaliniSKrantiMMadhuriR, et al.Identification of SGLT2 inhibitor ertugliflozin as a treatment for COVID-19 using computational and experimental paradigm. bioRxiv2021; 06.18.448921.
11.
ShaliniSKrantiMMadhuriR, et al.Tyrosine kinase inhibitor family of drugs as prospective targeted therapy for COVID-19 based on in silico and 3D-human vascular lung model studies. bioRxiv2021; 05.13.443955.
12.
ShaliniSKrantiMMadhuriR, et al.In silico and in vitro demonstration of homoharrintonine’s antagonism of RBD-ACE2 binding and its anti-inflammatory and anti-thrombogenic Pproperties in a 3D human vascular lung model. bioRxiv2021; 05.02.442384.
13.
ModafferiSZhongXKleensangA, et al. Gene–environment interactions in developmental neurotoxicity: A case study of synergy between chlorpyrifos and CHD8 knockout in human BrainSpheres. Environ Health Perspect2021; 129: 077001.
14.
BullenCKHogbergHTBahadirli-TalbottA, et al. Infectability of human BrainSphere neurons suggests neurotropism of SARS-CoV-2. ALTEX2020; 37: 665–671.
15.
TsujiKYamadaSHiraiK, et al.Development of alveolar and airway cells from human iPS cells: Toward SARS-CoV-2 research and drug toxicity testing. J Toxicol Sci2021; 46: 425–435.
16.
YuriKShigeruYKazuhiroN, et al.Clomipramine suppresses ACE2-mediated SARS-CoV-2 entry. bioRxiv2021; 03.13.435221.
17.
YamashitaMAokiHHashitaT, et al.Inhibition of transforming growth factor beta signaling pathway promotes differentiation of human induced pluripotent stem cell-derived brain microvascular endothelial-like cells. Fluids Barriers CNS2020; 17: 36.
18.
YamadaSKandaY. Retinoic acid promotes barrier functions in human iPSC-derived intestinal epithelial monolayers. J Pharmacol Sci2019; 140: 337–344.
19.
JangamreddyJRHaagdorensMKCMirazul IslamM, et al.Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants. Acta Biomater2018; 69: 120–130.
20.
FagerholmPLagaliNSMerrettK, et al.A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a Phase 1 clinical study. Sci Trans Med2010; 2(46): 46ra61.
21.
MirazulIslam MRavichandranROlsenD, et al.Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation. RSC Advances2016; 6: 55,745–55,749.
22.
DravidaSBiswasSVaranasiL. A new strategy to predict neurovirulence risk associated with Covid-19 vaccines — for seamless adoption. Pharma Focus Asia2021; 44: 34–37.
23.
DravidaSPalRKhannaA, et al.The transdifferentiation potential of limbal fibroblast-like cells. Brain Res Dev Brain Res2005; 160: 239–251.
24.
ArnesdotterESpinuNFirmanJ, et al.Derivation, characterisation and analysis of an adverse outcome pathway network for human hepatotoxicity. Toxicology2021; 459: 152856.
25.
GijbelsEVilas‐BoasVAnnaertP, et al.Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol2020; 94: 1151–1172.
26.
GijbelsEVinkenM. An update on adverse outcome pathways leading to liver injury. Appl In Vitro Toxicol2017; 3: 283–285.
27.
VinkenMLandesmannBGoumenouM, et al.Development of an adverse outcome pathway from drug-mediated bile salt export pump inhibition to cholestatic liver injury. Toxicol Sci2013; 136: 97–106.
28.
KandarovaH. Alternative methods to animal experimentation and their role in modern toxicology. In: TsatsakisAM (ed) Toxicological Risk Assessment and Multi-System Health Impacts from Exposure. Amsterdam: Elsevier, 2021, pp. 13–22.
29.
De JongWHHoffmannSLeeM, et al.Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts. Toxicol In Vitro2018; 50: 439–449.
30.
KandarovaHHaydenPJ. Standardised reconstructed skin models in toxicology and pharmacology: State of the art and future development. Handb Exp Pharmacol2021; 265: 57–71.
31.
National Research Council (US), Committee for the update of the guide for the care and use of laboratory animals. Guide for the Care and Use of Laboratory Animals, 8th edition. Washington, DC: National Academies Press, 2011, 246 pp.
32.
TuckerCBMacNeilMDWebsterAB (eds). Guide for the Care and Use of Agricultural Animals in Research and Teaching. Fourth Edition. USA: American Dairy Science Association®, American Society of Animal Science, Poultry Science Association, 2020, 227 pp.
33.
Council of Europe. Appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS No. 123) Guidelines for Accommodation and Care of Animals (Article 5 of the Convention). Strasbourg: Council of Europe, 2006, 109 pp.
BotteEBiaginiFMagliaroC, et al.Scaling of joint mass and metabolism fluctuations in in silico cell-laden spheroids. Proc Natl Acad Sci USA2021; 118: e2025211118.
36.
PernoldKIannelloFLowBE, et al.Towards large scale automated cage monitoring — Diurnal rhythm and impact of interventions on in-cage activity of C57BL/6J mice recorded 24/7 with a non-disrupting capacitive-based technique. PLoS One2019; 14: e0211063.
37.
GoltsteinPMReinertSGlasA, et al.Food and water restriction lead to differential learning behaviors in a head-fixed two-choice visual discrimination task for mice. PLoS One2018; 13: e0204066.
38.
GilesJMWhitakerJWMoySS, et al.Effect of environmental enrichment on aggression in BALB/cJ and BALB/cByJ mice monitored by using an automated system. J Am Assoc Lab Anim Sci2018; 57: 236–243.
39.
CalahorraJShenkJWielengaVH, et al.Hydroxytyrosol, the major phenolic compound of olive oil, as an acute therapeutic strategy after ischemic stroke. Nutrients2019; 11: 2430.
40.
IannelloF. Non-intrusive high throughput automated data collection from the home cage. Heliyon2019; 5: e01454.
41.
GoliniERigamontiMIannelloF, et al.A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS. Front Neurosci2020; 14: 896.
42.
TengelerACGartEWiesmannM, et al.Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr–/–. Leiden mice. FASEB J2020; 34: 9575–9593.
43.
JacobsSAHGartEVreekenD, et al.Sex-specific differences in fat storage, development of non-alcoholic fatty liver disease and brain structure in juvenile HFD-induced obese Ldlr–/–. Leiden mice. Nutrients2019; 11: 1861.
44.
TengelerACDamSAWiesmannM, et al.Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice. Microbiome2020; 8: 44.
45.
VoikarVGaburroS. Three pillars of automated home-cage phenotyping of mice: Novel findings, refinement, and reproducibility based on literature and experience. Front Behav Neurosci2020; 14: 575434.
46.
PernoldKRullmanEUlfhakeB. Major oscillations in spontaneous home-cage activity in C57BL/6 mice housed under constant conditions. Scientific Rep2021; 11: 4961.
47.
MorinFSinghNMdzombaJB, et al.Conditional deletions of Hdc confirm roles of histamine in anaphylaxis and circadian activity but not in autoimmune encephalomyelitis. Journal Immunol2021; 206: 2029–2037.
48.
FuochiSRigamontiMIannelloF, et al.Phenotyping spontaneous locomotor activity in inbred and outbred mouse strains by using Digital Ventilated Cages. Lab Anim2021; 50: 215–223.
49.
CorsiGPicardKCastroMA, et al.Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle. Glia2021; 70: 89–105.
50.
LohkampKJKiliaanAJShenkJ, et al.The impact of voluntary exercise on stroke recovery. Front Neurosci2021; 15: 695138.
51.
LavignaGMasoneABouybayouneI, et al.Doxycycline rescues recognition memory and circadian motor rhythmicity but does not prevent terminal disease in fatal familial insomnia mice. Neurobiol Dis2021; 158: 105455.
52.
ZentrichETalbotSRBleichA, et al.Automated home-cage monitoring during acute experimental colitis in mice. Front Neurosci2021; 15: 760606.
53.
BurmanOMarsellaGDi ClementeA, et al.The effect of exposure to low frequency electromagnetic fields (EMF) as an integral part of the housing system on anxiety-related behaviour, cognition and welfare in two strains of laboratory mouse. PLoS One2018; 13: e0197054.
54.
RecordatiCDe MaglieMMarsellaG, et al.Long-term study on the effects of housing C57BL/6NCrl mice in cages equipped with wireless technology generating extremely low-intensity electromagnetic fields. Toxicol Pathol2019; 47: 598–611.
55.
LloydKFranklinCLutzC, et al.Reproducibility: Use mouse biobanks or lose them. Nature2015; 522: 151–153.
BegleyCGEllisLM. Raise standards for preclinical cancer research. Nature2012; 483: 531–533.
58.
NewberryEPKennedySXieY, et al.Phenotypic divergence in two lines of L-Fabp–/– mice reflects substrain differences and environmental modifiers. Am J Physiol Gastrointest Liver Physiol2015; 309: G648–G661.
59.
WangBChandrasekeraPPippinJ. Leptin- and leptin receptor-deficient rodent models: Relevance for human type 2 diabetes. Curr Diabetes Rev2014; 10: 131–145.
60.
KilkennyCParsonsNKadyszewskiE, et al.Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One2009; 4: e7824.
61.
Percie du SertNAhluwaliaAAlamS, et al.Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol2020; 18: e3000411.
62.
WoodsSCLanghansW. Inconsistencies in the assessment of food intake. Am J Physiol Endocrinol Metab2012; 303: E1408–E1418.
63.
MacRaeCAPetersonRT. Zebrafish as tools for drug discovery. Nat Rev Drug Discov2015; 14: 721–731.
64.
HoweKClarkMDTorrojaCF, et al.The zebrafish reference genome sequence and its relationship to the human genome. Nature2013; 496: 498–503.
65.
CullyM. Zebrafish earn their drug discovery stripes. Nat Rev Drug Discov2019; 18: 811–813.
FazioMAblainJChuanY, et al.Zebrafish patient avatars in cancer biology and precision cancer therapy. Nat Rev Cancer2020; 20: 263–273.
68.
KulkarniPChaudhariGHSripuramV, et al.Oral dosing in adult zebrafish: Proof-of-concept using pharmacokinetics and pharmacological evaluation of carbamazepine. Pharmacol Rep2014; 66: 179–183.
69.
KulkarniPMedishettiRNuneN, et al.Correlation of pharmacokinetics and brain penetration data of adult zebrafish with higher mammals including humans. J Pharmacol Toxicol Methods2017; 88: 147–152.
70.
OECD. Guidelines for the Testing of chemicals. Test no. 236: Fish Embryo Acute Toxicity (FET) Test. Paris: Organisation for Economic Co-operation and Development, 2013, 22 pp.
71.
Panzica-KellyJMZhangCXDanberryTL, et al.Morphological score assignment guidelines for the dechorionated zebrafish teratogenicity assay. Birth Defects Res B Dev Reprod Toxicol2010; 89: 382–395.
72.
ChaudhariGHChennubhotlaKSChattiK, et al.Optimization of the adult zebrafish ECG method for assessment of drug-induced QTc prolongation. J Pharmacol Toxicol Methods2013; 67: 115–120.
73.
KulkarniP. Zebrafish Models for Neuroscience Drug Discovery [PhD Thesis]. Pilani: Birla Institute of Technology and Science, 2018.
74.
DwivediSMedishettiRRaniR, et al.Larval zebrafish model for studying the effects of valproic acid on neurodevelopment: An approach towards modeling autism. J Pharmacol Toxicol Methods2019; 95: 56–65.
75.
HillAMesensNSteemansM, et al.Comparisons between in vitro whole cell imaging and in vivo zebrafish-based approaches for identifying potential human hepatotoxicants earlier in pharmaceutical development. Drug Metab Rev2012; 44: 127–140.
MedishettiRRaniRKavatiS, et al.A DNAzyme based knockdown model for Fragile-X syndrome in zebrafish reveals a critical window for therapeutic intervention. J Pharmacol Toxicol Methods2020; 101: 106656.
78.
PedersenHDMikkelsenLF. Göttingen Minipigs as large animal model in toxicology. In: GuptaRC (ed). Biomarkers in Toxicology. Second edition.Amsterdam: Elsevier; 2019, pp. 75–89.
79.
HarrisonRK. Phase II and phase III failures: 2013–2015. Nat Rev Drug Discov2016; 15: 817–818.
80.
VangalaSPinjariJPatoleP, et al.Translational drug discovery research: Integration of medicinal chemistry, computational modeling, pharmacology, ADME, and toxicology. In: LyubimovAV (ed) Encyclopedia of Drug Metabolism and Interactions. Part III: General principles of ADME. Hoboken, NY: Wiley, 2012, pp. 1–54.
81.
WilliamsJAAnderssonTAnderssonTB, et al.PhRMA white paper on ADME pharmacogenomics. J Clin Pharmacol2008; 48: 849–889.
82.
EichenbaumGVangalaSTonelliAP. Toxicokinetics in support of drug development. In: CayenMN (ed) Early Drug Development: Strategies and Routes to First‐in‐Human Trials. Hoboken, NY: Wiley, 2010, pp. 309–359.
VangalaSUdaySSatishchandranC. Building human in vitro 3D models to replace animal studies during drug discovery research: Scientific, ethical and regulatory considerations, 2022 (In Press).
85.
IsgutMRaoMYangC, et al.Application of combination high-throughput phenotypic screening and target identification methods for the discovery of natural product-based combination drugs. Med Res Rev2017; 38: 504–524.
86.
VangalaSKolachanaP. Endogenous toxins as disease initiating events: Future targets of drug discovery research. J Anal Pharm Res2016; 2: 00036.
87.
Maria-EnglerSS. Harnessing skin reconstruction for testing topical agents in a healthy and diseased skin. Toxicol Lett2016; 259: S45.
88.
MassaguerPXRMillásALGM. The Brazilian sectoral innovation system in the field of tissue engineering and bioprinting: Actors, challenges and perspectives. IJAMB2019; 2: 33.
89.
MillasALGMcKeanRStevensR, et al.Fabrication of electrospun scaffolds incorporating an Amazonian therapeutic oil from the Copaifera species for wound care applications. J Biomater Tissue Eng2014; 4: 217–220.
90.
MillásALagoJVasquez-PintoL, et al.Approaches to the development of 3D bioprinted skin models: The case of Natura Cosmetics. IJAMB2019; 2: 3.
91.
JuYWuXTanG, et al.First report of Meloidogyne graminicola on rice in Anhui Province, China. Plant Dis2021; 105: 512–512.
