Hepatology - Tissue engineering Flashcards
What are risk factors for a need for LTx? (4)
- Rare & genetic causes
- Viruses
- Alcohol intake
- Obesity
Why is liver tissue engineering necessary? (2)
- Donor shortage
- Lower quality of donor organs
What causes a lower quality of donor organs? (3)
- Increasing population age
- Increasing alcohol intake
- Increased obesity
What are the strategies for liver tissue engineering? (4)
- Living donor LTx
- Revive non-transplantable livers
- Tissue engineer livers
- (Stem)cell therapy to improve liver quality
What is the downside of using donor livers from extended criteria donors?
Suboptimal graft -> higher chance of post-Tx complications
What are characteristics of extended criteria donors? (5)
- Advanced donor age
- BMI
- Donor after circulatory death (DCD)
- > max time circulation arrest
- Increased liver enzymes
Which two options are there for graft storage between donor and recipient?
- Static cold storage (=ice bag)
- Dynamic liver preservation (=machine perfusion)
Which two strategies of machine perfusion are there for livers?
- Hypothermic: 4-10 °C
- Normothermic: 37 °C
What is the advantage of normothermic machine perfusion?
More physiological
What are the advantages of machine perfusion over static cold storage?
- Monitoring & improvement of graft quality
- Improving graft preservation
- Reduction of ischaemia
Which interventions are possible during machine perfusion of livers? (7)
- Mesenchymal stem cell infusion
- iPSC/organoid infusion
- Gene-corrected cell infusion
- Removal of debris & dead cells
- Drugs to reverse steatosis
- Antibiotic infusion
- Anti-inflammatory treatment
Why would it be useful to be able to regenerate and/or expand livers during machine perfusion?
Liver expansion would allow for a splitting of the liver, possibly helping 2 patients with 1 liver
What is the goal of tissue engineering?
Create new tissues/cells to heal organs or create entirely new organs
What are the used of engineered liver tissues? (4)
- Toxicological studies
- Drug testing
- Disease modelling
- Clinical applications
Which components are needed to engineer a liver? (3)
- Cells
- Scaffold: ECM
- Biologicals
Which cells would be needed to engineer a liver? (2x2)
Parenchyma:
1. Hepatocytes
2. Cholangiocytes
Stroma:
1. Stellate cells
2. Kupffer cells
Which ECM components would be needed to engineer a liver? (3)
- Collagens
- Laminins
- Other ECM proteins
Which biologicals would be needed to engineer a liver? (2)
- Growth factors
- Glycosaminoglycans
What is the process of liver decellularization? (5)
- Removal of blood using heparin solution
- Decelluarization using Triton X-100 solution
- Rinse using NaCl
- ENdonuclease treatment to remove DNA sticking to ECM
- Freeze & store
Which conditions need to be met for successful decellularlization? (3)
- No cells left
- ECM proteins unaffected
- Liver architecture remains (vascular + biliary system)
Decellularized livers are hypothesized not to trigger the immune system. Why?
No HLA-molecules present
Which steps in liver matrix recellularization have already been succesfully performed? Which step still needs to be taken?
Succesfully performed:
1. Bile duct recellularization
2. Revascularizatoin
Step still to be taken: recellularization of the hepatocyte compartment
What are the applications of liver organoids?
- Toxicology
- Comparison of models
- Drug screening
- Application in clinical genetics
- Study of liver disease
