Cell models + neuro stemcel models
17 important questions on Cell models + neuro stemcel models
What are challenges of cell models?
- Which model should you use? => what suits the best for your disease and phenotype?
- ..
What are the different levels of cell models. Give from each one an example.
Patient cells or pluripotent cells.
2. 3D: sheroids and organoids and scaffolds
3. Bone cells in their native matrix
4. Dynamic culture.
Name different reasons why animal models are not ideal.
- Rodent vs human => they walk on four legs
- Ethical reasons
- Higher grades + faster learning
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Instead of using biopsy material for 2D models you can also use stemcells or other cells. Descibe + why important for personalized medicine?
It allows modeling of complex genetic profile that can increase risk on developing disease
Why is it important to use iPSC cells specific from the patients?
What do you need to make pluri/multi potent stemcells?
What is the difference between spheroids and organoids?
- Spheroids are simple, widely used multicellular 3D models that form due to the tendency of adherent cells to aggregate. Spheroids can be generated from a broad range of cell types including tumor spheroids, embryoid bodies, hepatospheres, neurospheres, and mammospheres.
- An organoid is a self-organized 3D tissue that is typically derived from stem cells (pluripotent, fetal or adult), and which mimics the key functional, structural and biological complexity of an organ
Which steps are needed before clinical application? Name an example in which this worked.
- Test in the lab
- Use of animal models => still needed
- Clinical studies.
Clinical use of adipose tissue derived from stem cells.
What is important in creating tissue complexity.
- To establish relevant assay systems that more closely simulate the cellular and molecular microenvironment encountered in a specific situation
- Cells in their native matrix
- Cell–cell and cell–material interactions.
Measure RNA analysis to look at the impact of the native matrix.
Name an example of a dynamic/multy tissue.
- The tool (MechanoCHIP) will consist of a microfluidic cell culture platform that can screen the cytostatic effect of pharmaceuticals on cancer cells in a system that realistically mimics the in vivo situation.
- Co-culture of human osteoblasts with prostate or breast-cancer cells on 2 sides of a fibronectin-coated tissue culture insert.
- Test situations with compressive and shear stress
What are organ-on-chips?
What are challenges for development of bone-on-chip models?
- Cell types with different cell lineages = cell division
- Matrix components are complex
- ..
What are problems of using animal models for neuro translational studies in humans? So why do animal studies not decline?
iPSC studies often do not model complex brain network:
- No single model replaces the whole mouse: multi-level analysis provides deep insight into mechanisms
- iPSC models are (so far) not suitable for studies sensory signal processing (e.g. learning, social and motor behavior, memory)
Not standardized
What kind of cells do they use for iPSC?
- Fibroblasten
What is very important in modeling neuronal models?
- oligodendrocytes + neurons
- astrocytes + neurons
What are goals of models?
- See what happens in the cell => relate this to clinical features (example of new knowledge that plasma VLCFA levels do not impact the severity of the disease)
What is important to reduce bias + increase reproducibility?
- Checking between-subject variation
- Checking within-subjects variation: different iPSC clones form the same donor
- Checking technical variation: with the same clone iPSC model
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