Lesson 1Selectin in vitro models: organoids, co-culture systems, 2D vs 3D scaffolds an disease-relevant readoutsDis section discuss selection an design a in vitro models, includin 2D cultures, 3D scaffolds, organoids, an co-culture systems, wid emphasis pon microenvironmental cues, disease-relevant readouts, throughput, an alignment wid in vivo findins.
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 an rat disease models relevant to chosen indication an translatability limitsDis section focus pon small animal models, mainly mouse an rat, describin disease models relevant to regenerative indications, genetic tools, immune backgrounds, practical advantages, an key limitations fi predictin human safety an 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 3Dosin strategies an kinetics: cell dose-rangin studies, biodistribution, an persistence analysisDis section explain dosin strategies fi cell therapies, includin dose-rangin designs, single versus repeat dosin, route-dependent dose adjustments, biodistribution mappin, persistence an engraftment analysis, an modelin 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 fi scale-up an functional similarityDis section examine large animal models such as pig, sheep, an non-human primates, focusin pon anatomical an physiological similarity, immune context, housin an welfare, scalin a devices an doses, an when large models essential fi 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, imagiin modalities (MRI, PET, bioluminescence), molecular biomarkers, an behavioral testsDis section detail how to select an validate outcome measures, includin histology, functional assays, imagiin modalities, molecular biomarkers, an behavioral tests, emphasizin sensitivity, specificity, quantification, an relevance to human clinical benefit.
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 an device-assisted delivery: intravenous, intra-organ, intra-articular, biomaterial scaffolds, an catheter-based techniquesDis section review delivery routes an device-assisted methods fi cell an gene-modified products, includin intravenous, intra-organ, intra-articular, scaffold-based, an catheter techniques, highlightin targetin efficiency, safety, an technical feasibility.
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, randomization, blindin, sample size calculation, an statistical endpointsDis section introduce rigorous preclinical study design, from definin hypotheses an selectin controls to randomization, blindin, sample size calculation, an statistical endpoints, aimin to reduce bias an improve reproducibility an regulatory acceptance.
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 sourcin, manufacturin an GMP considerations fi preclinical batches: isolation, expansion, cryopreservation, an release criteriaDis section cover sourcin an manufacturin a preclinical cell batches, includin tissue selection, isolation, expansion, cryopreservation, quality control, GMP compliance, an release criteria to ensure consistent, safe, an well-characterized 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
