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Clinical trials (3)

Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s P rogrammes at the University of Pécs and at the University of Debrecen Identification number : TÁMOP-4.1.2-08/1/A-2009-0011.

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Clinical trials (3)

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  1. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identificationnumber: TÁMOP-4.1.2-08/1/A-2009-0011

  2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Dr. Judit Pongrácz Threedimensionaltissuecultures and tissueengineering – Lecture 25 Clinicaltrials(3)

  3. Tissue engineered blood vessel • TE bloodvesselsareusedonlyinlowpressurepulmonarycirculation • Thesegraftsarenotdurableenoughtowithstandhigharterialpressure Cellisolation Cellexpansion Small-vein harvest Cellseeding onpolymer Tissue-engineeredgraft

  4. TEBV production • A completelybiologicaltissue-engineered human bloodvessel (Nicolas L'heureux, StéphaniePâquet, Raymond Labbé, LucieGermain, and François A. Auger ) FASEB Journal 1998 • HUVEC and SMC wereused

  5. Myocardialinfaction • Stemcellsareusedincasesfollowingextensivedamage • In most casesimprovement is shownbutfurtherstudiesareneeded

  6. Urethra and bladder • Acellularcollagen-basedmatrices • Intestinalorbladderepithelialcells • 4-7 yearslater 34 out of 40 patients had a successfuloutcome

  7. Cartilage • Twomulticentreclinicaltrials • In most casesimprovementwasnoted • Long termeffectsarestill being considered

  8. Lung

  9. Trachea - bronchi - lungs

  10. Lungdiseasesbenefitingfromcellbasedtherapies • COPD (chronicobstuctivepulmonarydisease) • ARDS (acuterespiratorydistresssyndrome) • Asthma • Mechanicaltissuedamages

  11. Strategiesforcell-basedtherapiesforthelung Embryonicstemcells Culture Pulmonaryepithelium Selection (genetic, air liquidinterface, mediaco-culture) Mesenchyme Endothelium Pulmonaryepithelial-likecells Organoid Functional unit ESCs, MSCs, Fibrocytes Intratracheal/Vascularinfusion Structuralgrafts Engraftment Genetransfer Delivery of therapeutic molecules Acutecytoprotection/repair (survival, growthfactors) Engraftment Cartilage Vasculature Epithelium Stroma (fibroblast)

  12. Complexity of lungstructuresduringdevelopment Es Es T T Lungbud Type I cell TypeII cell Columnarcells Gobletcell Ciliated cell Claracell Basal cell Fibroblasts I. Embryonic E 9-12 II. Pseudoglandular E 12-15 III. Canalicular E 15-E17 IV. Saccular E 17-Birth V. Alveolar Birth-PN20

  13. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Dr. Judit Pongrácz Threedimensionaltissuecultures and tissueengineering – Lecture 26 Research application and drug testing

  14. Research applications • Intercellularinteraction • Study of Signalingpathway (inter and intra-cellular) • Study of regenerationprocesses • Modelingdiseases

  15. Thymusreaggregation E15 mouseembryo E15 thymiclobes Deoxiguanosinecultures T-lymphocytesor lymphoidprogenitors Thymicepithelialcells Reaggregate

  16. Thymocytedevelopmentinthereaggregatedthymus Stromalcell Jagged/Delta-like Presenilin g-Secretase Lymphocyte progenitor IntracellularNotch (ICN) CoR Nucleus CoA CoR CSL (ICN) CSL • No T-cellcommitment • AllowsB-cellcommitment • InducesT-cellcommitment • BlocksB-cellcommitment

  17. Salivaryglandaggregate GFP-Ad FoxN1-Ad

  18. Tissuespecificchanges • Expression of transcriptionfactors and othergenesareeasilymodified • Geneexpressionmodification is tissuetyperestricted • Effectsonthewholetissuecan be studiedatthelevel of morphology, cellularinteractions and signaling

  19. Drug testing • Toxicity testing • Efficacy testing

  20. Hepatotoxicity testing • Purifiedprimary human hepatocytesin 2D • Complex 3D livermicro-tissuesfortoxicity • Toxicity testing (acute and chronic) • Viabilityassays • Bileproduction • Molecular marker tests (albumin etc)

  21. Lungmodelfordrug testing • Complexcellularcomposition • Closetophysiologicaldrugtransporterexpression • Easyhandling • Suitabilityfor HTS

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