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

2. CLINICAL TRIALS (3) Dr. Judit Pongrácz Three dimensional tissue cultures and tissue engineering – Lecture 25 Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

3. TÁMOP-4.1.2-08/1/A-2009-0011 Tissue engineered blood vessel TE blood vessels are used only in low pressure pulmonary circulation These grafts are not durable enough to withstand high arterial pressure Small-veinharvest Cell seeding on polymer Cell isolation Cell expansion Tissue-engineered graft

4. TÁMOP-4.1.2-08/1/A-2009-0011 TEBV production A completely biological tissue- engineered human blood vessel (Nicolas L'heureux, Stéphanie Pâquet, Raymond Labbé, Lucie Germain, and François A. Auger ) FASEB Journal 1998 HUVEC and SMC were used

5. TÁMOP-4.1.2-08/1/A-2009-0011 Myocardial infaction Stem cells are used in cases following extensive damage In most cases improvement is shown but further studies are needed

6. TÁMOP-4.1.2-08/1/A-2009-0011 Urethra and bladder Acellular collagen-based matrices Intestinal or bladder epithelial cells 4-7 years later 34 out of 40 patients had a successful outcome

7. TÁMOP-4.1.2-08/1/A-2009-0011 Cartilage Two multicentre clinical trials In most cases improvement was noted Long term effects are still being considered

8. TÁMOP-4.1.2-08/1/A-2009-0011 Lung

9. TÁMOP-4.1.2-08/1/A-2009-0011 Trachea - bronchi - lungs

10. TÁMOP-4.1.2-08/1/A-2009-0011 Lung diseases benefiting from cell based therapies COPD (chronic obstuctive pulmonary disease) ARDS (acute respiratory distress syndrome) Asthma Mechanical tissue damages

11. TÁMOP-4.1.2-08/1/A-2009-0011 Strategies for cell-based therapies for the lung Pulmonary epithelial-like cells Embryonic stem cells Culture Selection (genetic, air liquid interface, media co-culture) Epithelium Vasculature Stroma (fibroblast) ESCs, MSCs, Fibrocytes Acute cytoprotection/repair (survival, growth factors) Cartilage Intratracheal/Vascular infusion Structural grafts Engraftment Gene transfer Delivery of therapeutic molecules Engraftment Organoid Functional unit Endothelium Pulmonary epithelium Mesenchyme

12. TÁMOP-4.1.2-08/1/A-2009-0011 Complexity of lung structures during development Columnar cells Fibroblasts Goblet cell Basal cell Ciliated cellClara cell Type I cell Type II cell I.Embryonic E 9-12 II.Pseudoglandular E 12-15 III.Canalicular E 15-E17 IV.Saccular E 17-Birth V.AlveolarBirth-PN20 Lung bud Es TT

13. RESEARCH APPLICATION AND DRUG TESTING Dr. Judit Pongrácz Three dimensional tissue cultures and tissue engineering – Lecture 26 Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

14. TÁMOP-4.1.2-08/1/A-2009-0011 Research applications Intercellular interaction Study of Signaling pathway (inter and intra-cellular) Study of regeneration processes Modeling diseases

15. TÁMOP-4.1.2-08/1/A-2009-0011 Thymus reaggregation E15 mouse embryo T-lymphocytes or lymphoid progenitors Deoxiguanosine cultures Thymic epithelial cells E15 thymic lobes Reaggregate

16. TÁMOP-4.1.2-08/1/A-2009-0011 Thymocyte development in the reaggregated thymus Intracellular Notch (ICN) No T-cell commitment Allows B-cell commitment Induces T-cell commitment Blocks B-cell commitment Nucleus Stromal cell Lymphocyte progenitor Jagged/Delta-like CSL CoR CoA Presenilin  -Secretase Presenilin  -Secretase CoR (ICN)

17. TÁMOP-4.1.2-08/1/A-2009-0011 Salivary gland aggregate GFP-AdFoxN1-Ad

18. TÁMOP-4.1.2-08/1/A-2009-0011 Tissue specific changes Expression of transcription factors and other genes are easily modified Gene expression modification is tissue type restricted Effects on the whole tissue can be studied at the level of morphology, cellular interactions and signaling

19. TÁMOP-4.1.2-08/1/A-2009-0011 Drug testing Toxicity testing Efficacy testing

20. TÁMOP-4.1.2-08/1/A-2009-0011 Hepatotoxicity testing Purified primary human hepatocytes in 2D Complex 3D liver micro-tissues for toxicity Toxicity testing (acute and chronic) Viability assays Bile production Molecular marker tests (albumin etc)

21. TÁMOP-4.1.2-08/1/A-2009-0011 Lung model for drug testing Complex cellular composition Close to physiological drug transporter expression Easy handling Suitability for HTS