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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

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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

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)

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-vein harvest

Cell seeding on polymer Cell isolation

Cell expansion

Tissue-engineered graft

(4)

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)

Myocardial infaction

• Stem cells are used in cases following extensive damage

• In most cases improvement is shown but further studies are needed

(6)

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)

Cartilage

• Two multicentre clinical trials

• In most cases improvement was noted

• Long term effects are still being considered

(8)

Lung

(9)

Trachea - bronchi - lungs

(10)

Lung diseases benefiting from cell based therapies

• COPD (chronic obstuctive pulmonary disease)

• ARDS (acute respiratory distress syndrome)

• Asthma

• Mechanical tissue damages

(11)

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)

Complexity of lung structures during development

Columnar cells

Fibroblasts

Goblet cell

Basal cell

Ciliated cell Clara 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.

Alveolar Birth-PN20

Lung bud

Es Es

T T

(13)

RESEARCH

APPLICATION AND DRUG TESTING

Dr. Judit Pongrácz

Three dimensional tissue cultures and tissue engineering – Lecture 26

at the University of Pécs and at the University of Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

(14)

Research applications

• Intercellular interaction

• Study of Signaling pathway (inter and intra-cellular)

• Study of regeneration processes

• Modeling diseases

(15)

Thymus reaggregation

E15 mouse embryo

T-lymphocytes or lymphoid progenitors

Deoxiguanosine cultures

Thymic epithelial cells E15 thymic lobes

Reaggregate

(16)

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 CSL

CoR CoA

Presenilin g-Secretase

CoR

(ICN)

(17)

Salivary gland aggregate

GFP-Ad FoxN1-Ad

(18)

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)

Drug testing

• Toxicity testing

• Efficacy testing

(20)

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)

Lung model for drug testing

• Complex cellular composition

• Close to physiological drug transporter expression

• Easy handling

• Suitability for HTS

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