16. Modelling Organogenesis In Vitro Flashcards
(19 cards)
What is the primary aim of in vitro models?
To recapitulate aspects of organ development
Complete modeling of in vivo complexity is impossible
List the specific elements that need to be modeled in in vitro systems.
- Cell differentiation
- Spatial organization
- Three-dimensional architecture
- Cell-cell interactions
- Matrix interactions
- Mechanical forces
What are the limitations of traditional 2D cell culture?
- Cells spread unnaturally
- Altered cytoskeleton
- Changed gene expression
- No matrix interaction
- No tissue-like mechanical forces
What is the first step in the evolution of cell culture systems?
Basic 2D culture: Cells on glass/plastic (artificial environment)
What is the purpose of matrix supplementation in cell culture?
To add ECM proteins to media (e.g., laminin)
What is an organoid?
Self-organizing 3D structures that resemble organ-specific architecture with multiple cell types
What historical developments contributed to organoid technology?
- Mouse embryonic stem cells (1980s)
- Human embryonic stem cells (2000s)
- Induced pluripotent stem cells (iPSCs) (2006+)
Which signaling pathways drive different germ layers in organoid creation?
- Wnt signaling
- FGF signaling
- Retinoic acid
- TGF-β/BMP balance
What types of organoids have been successfully created?
- Intestinal organoids
- Kidney organoids
- Cerebral organoids
- Liver organoids
What is the focus of tissue engineering approaches?
Scaffolds and 3D structures
What is the purpose of organ-on-a-chip systems?
To provide simplified, reproducible model systems for drug testing
What are the mechanical properties of articular cartilage?
- Anisotropic collagen orientation in different zones
- Responds to shear and compressive forces
- Cell phenotype depends on 3D environment
What is the process of modeling human disease using iPSC technology?
- Take patient skin biopsy with genetic condition
- Reprogram to iPSCs
- Differentiate to relevant tissue type
- Analyze disease phenotype
List the types of mechanical forces involved in development.
- Tension (actin-myosin contraction)
- Surface tension
- Osmotic pressure
- Tethering forces
- Shear stress
- Compression
- Torsion
What are some methods used to study mechanical forces?
- Computational modeling of fluid flow
- Spatial transcriptomics
- Micromanipulation techniques
- Atomic force microscopy
- Traction force microscopy
- Microfluidic systems
What are the advantages of in vitro models?
- Tractability and cost-effectiveness
- Human cell compatibility
- Disease modeling capabilities
- Drug screening applications
- Can integrate engineered components
- Allow manipulation of mechanical environments
True or False: 2D culture systems are adequate for modeling organogenesis.
False
What modern approaches are integrated to improve modeling of organogenesis?
- Developmental biology
- Engineering
- Biomechanics
What is a key conclusion about in vitro models?
They cannot fully recapitulate in vivo development but are a valuable complementary approach