Organ on a chip

Question 1

What is the goal of developing complex 3D organ/tissue models?

Answer 1

A journey towards the development 3D culture systems that support and steer in vivo-like cell behavior, to enable more accurate models of human (patho-)physiology and response to treatment.

Question 2

Name benefits of 2D cell cultures.

Answer 2

• Well-established → large data sets to compare to for quality control and performance.
• Accessibility of high-resolution data → possible to analyse cell behavior with high-resolution.
• Ease of use → non-technical, reduced space, relatively inexpensive.
• High throughput → possibility for automated, large-scale, high-throughput experimentation.

Question 3

Name drawback of 2D cell cultures.

Answer 3

• 2D cell culture is highly artificial
• Reduced cellular diversity
• Lack of nutrient, oxygen and waste gradients
• No mechanical input
• Abnormal or suboptimal polarization

Resulting in a reduced prediction of in vivo results

Question 4

Name advantages of 3D cell cultures.

Answer 4

• Natural gradient formation: spatially dependent cell behavior
• Increased cellular diversity: modelling physiological processes.
• Physiologically relevant mechanical forces
• In vivo-like cell morphology and gene expression

And thus mimicry of human-relevant microenvironments.

Question 5

A type of 3D models, are the spherical culture models (spheroids and organoids). Describe characteristics of this type of 3D model.

Answer 5

• Cells are cultured in a 3D mass (with or without) extracellular matrix.
• Applications include stem cell niches and tumor microenvironment models.
• Drawbacks → limited perfusion/mechanical cues and abnormal architecture.

Question 6

Organs-on-chips is another type of 3D model. Describe the characteristics of this type of 3D model.

Answer 6

• Recapitulation of tissue-level architecture, supported by tissue-specific ECM proteins.
• Structurally defined framework allowing heterogeneous cell populations and mechanical cues.
• Realistic models of in vivo physiology, used to study numerous organs and diseases.

Question 7

Question 8

Name advantages of organs-on-a-chip.

Answer 8

Organization and spatial precision:
- precise location and organization of cells/ECM
- tissue-tissue interfaces

Biomimetic stimuli control:
- Physiological-like stimuli: mechanical, electrical and/or chemical
- Fluid flow and organ/tissue communication via micro-channels
- Spatial-temporal control of secreted signals

Multi-organ interactions:
- Systemic-like interface via vascular coupling of organs
- Coupling with components of the immune system

Question 9

Future directions

Question 10

Take home message