L16 - Organs-on-a-chip

Question 1

What are the issues with current models in drug development?

Answer 1

They are not accurately predicting the human response

Question 2

Issues

Answer 2

In vitro
- Primary cells; source and viability 
- Transformed; may have altered phenotype 
- Stem cells; not primary cells
In vivo
- Animal models; not always guaranteed

Question 3

What is an O-O-A-C?

Answer 3

Perfused, micrometer-sized chambers in which cells are cultured
Incorporation of minimal units that mimic tissue/organ-level functions

Question 4

What are the typical components of OOAC?

Answer 4

Geometric confinement and patterning
Presence of flow
Environmental control
Sensors and physiological readout

Question 5

Lung-on-a-chip

Answer 5

Chip has lower layer, porous membrane and upper layer
Epithelial cells on one side of membrane (alv) and endo on the other (cap).
Increase surfactant after exposure to air
Side chamber - connected to vaccume for cyclical stretching

Question 6

Modelling pulmonary inflammation

Answer 6

Cytokines released by epithelium (TNFa)
Activation of endothelium (ICAM-1)
Leukocyte infiltration into alveoli side

Question 7

Modelling pulmonary edema

Answer 7

Excess fluid build up in lungs
Fluid moves from blood to alveoli
Added IL-2 to mimic oedema - increase permeability of oedema
Ang-1; shown to stabilise junction between endothelial cells
Ang-2; Ang-1 antag