Lesson 1Selecting in vitro models: organoids, co-culture systems, 2D vs 3D scaffolds and disease-relevant readoutsThis lesson discusses the selection and design of in vitro models, such as 2D cultures, 3D scaffolds, organoids, and co-culture systems, with focus on cues from the microenvironment, readouts relevant to diseases, throughput, and correlation with in vivo 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 focuses on small animal models, primarily mice and rats, describing disease models applicable to regenerative indications, genetic tools, immune contexts, practical benefits, and main limitations in forecasting human safety and efficacy.
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 strategies for cell therapies, including designs for dose-ranging, single versus repeated dosing, adjustments based on route, mapping of biodistribution, analysis of persistence and engraftment, and modelling of exposure-response relationships.
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 examines large animal models like pigs, sheep, and non-human primates, emphasising anatomical and physiological similarities, immune settings, housing and welfare, scaling of devices and doses, and when 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 details the selection and validation of outcome measures, including histology, functional assays, imaging methods, molecular biomarkers, and behavioural tests, stressing sensitivity, specificity, quantification, and relevance to human clinical benefits.
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 reviews delivery routes and methods assisted by devices for cell and gene-modified products, including intravenous, intra-organ, intra-articular, scaffold-based, and catheter techniques, highlighting efficiency of targeting, safety, and technical viability.
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 principles of rigorous preclinical study design, from defining hypotheses and choosing controls to randomisation, blinding, sample size calculations, and statistical endpoints, to minimise bias and enhance reproducibility and regulatory approval.
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 covers sourcing and manufacturing of preclinical cell batches, including selection of tissues, isolation, expansion, cryopreservation, quality control, GMP compliance, and release criteria to guarantee consistent, safe, and well-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
