Lesson 1Selecting in vitro models: organoids, co-culture systems, 2D vs 3D scaffolds and disease-relevant readoutsThis lesson discusses choosing and designing in vitro models, such as 2D cultures, 3D scaffolds, organoids, and co-culture setups, with focus on environmental signals, readouts relevant to diseases, efficiency, and correlation with animal study results.
2D monolayer versus 3D culture systemsOrganoid models for organ-specific diseasesCo-culture and immune–stromal interactionsBiomaterial scaffolds and matrix mechanicsAssay readouts linked to in vivo outcomesThroughput, scalability, and assay robustnessLesson 2Small animal models: mouse and rat disease models relevant to chosen indication and translatability limitsThis lesson centres on small animal models, primarily mice and rats, describing disease models applicable to regenerative treatments, genetic tools, immune profiles, practical benefits, and main limitations in forecasting human safety and effectiveness.
Mouse versus rat: strengths and weaknessesImmunodeficient and humanized rodent modelsCommon disease models for key indicationsModel validation and relevance to humansLimitations in scale, immunity, and lifespanBridging data to large animals and clinicsLesson 3Dosing strategies and kinetics: cell dose-ranging studies, biodistribution, and persistence analysisThis lesson explains dosing approaches for cell therapies, covering dose-ranging experiments, single or repeated dosing, adjustments based on delivery route, mapping of biodistribution, analysis of persistence and engraftment, and modelling of exposure-response links.
Design of dose-escalation and range-findingSingle versus multiple dosing regimensLabeling cells for tracking in vivoBiodistribution assessment and organ tropismPersistence, engraftment, and clearance kineticsExposure–response and safety margin modelingLesson 4Large animal models: pig, sheep, non-human primate choices for scale-up and functional similarityThis lesson reviews large animal models including pigs, sheep, and non-human primates, emphasising anatomical and physiological similarities, immune contexts, care and welfare, scaling of doses and devices, and situations where large models are crucial for translation.
Criteria for choosing large animal speciesPig models for cardiovascular and liver repairSheep models for orthopedic and spine studiesNon-human primate models and ethicsScaling of devices, doses, and proceduresHusbandry, welfare, and regulatory oversightLesson 5Outcome measures: histology, functional assays, imaging modalities (MRI, PET, bioluminescence), molecular biomarkers, and behavioural testsThis lesson explains selecting and validating outcome measures like histology, functional tests, imaging techniques, molecular biomarkers, and behavioural assessments, stressing sensitivity, specificity, quantification, and connection to human clinical outcomes.
Histological scoring and morphometric analysisIn vitro and ex vivo functional assaysMRI, PET, and optical imaging strategiesMolecular biomarkers and omics readoutsBehavioral tests and functional performanceValidation, standardization, and assay QCLesson 6Delivery routes and device-assisted delivery: intravenous, intra-organ, intra-articular, biomaterial scaffolds, and catheter-based techniquesThis lesson covers delivery routes and device-supported methods for cell and gene-modified products, such as intravenous, intra-organ, intra-articular, scaffold-based, and catheter approaches, focusing on targeting accuracy, safety, and practical implementation.
Intravenous and intra-arterial deliveryDirect intra-organ and parenchymal injectionIntra-articular and intradiscal approachesBiomaterial scaffolds and hydrogelsCatheter-based and image-guided deliveryProcedure-related risks and mitigationLesson 7Study design principles: hypotheses, controls, randomisation, blinding, sample size calculation, and statistical endpointsThis lesson introduces solid preclinical study design principles, from establishing hypotheses and controls to randomisation, blinding, sample size calculations, and statistical endpoints, to minimise bias and boost reproducibility and acceptance by regulators.
Formulating testable mechanistic hypothesesChoice of control and comparator groupsRandomization schemes and allocation concealmentBlinding of investigators and outcome assessorsSample size and power calculationsPrimary, secondary, and exploratory endpointsLesson 8Cell sourcing, manufacturing and GMP considerations for preclinical batches: isolation, expansion, cryopreservation, and release criteriaThis lesson addresses sourcing and manufacturing of cells for preclinical use, including tissue choice, isolation, expansion, cryopreservation, quality checks, GMP standards, and release criteria to produce consistent, safe, and thoroughly characterised products.
Donor selection and tissue procurementCell isolation and early characterizationExpansion, passaging, and senescence controlCryopreservation methods and thaw recoveryGMP documentation and batch recordsRelease testing and specification setting
