2 Neuroscience2.3 Basic techniques in neuroscience
2.3.4 Cellular disease models
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Written by Resident Doctor Committee · Published
New in the 2027 syllabus
The College added this topic for exams from January 2027.
From patient to model
Induced pluripotent stem cells (iPSCs) are somatic (body) cells reprogrammed back into a stem-cell state. They can then be turned into neurones or glia, and they keep the donor's inherited deoxyribonucleic acid (DNA) variants.
Two-dimensional cultures are flat layers of cells. They are easier to reach than three-dimensional tissue, so you can measure cell survival, neurite growth, receptor function and electrical activity under controlled conditions.
Organoids organise themselves into three-dimensional structures partly like brain tissue. They model aspects of development, not a complete, working adult brain.
Designing a useful experiment
Design choice | What it does | What it still cannot fix |
|---|---|---|
Several donors and independent clones | Tests whether a finding holds beyond one person or line | Differences in genetic background remain |
Isogenic gene correction | Compares cells that differ only at the targeted variant | Editing artefacts and clone effects need checking |
Defined cell identity and maturity | Confirms which cells the assay is actually measuring | Cultures often look like immature tissue |
Replicated differentiation batches | Picks up technical variability | Batch effects can mimic disease effects |
Rescue or perturbation experiment | Tests whether changing a pathway changes the phenotype | A rescue in cells does not prove clinical benefit |
What the model cannot establish
Missing parts may include mature blood vessels (vasculature), immune interactions and sensory experience. In organoids, hypoxia (lack of oxygen) and an uneven mix of cell types can distort findings.
Reprogramming can wipe out some age-related features of the cell. This limits direct modelling of late-life neurodegeneration.
A phenotype linked to the disease supports a cellular hypothesis. It cannot reproduce a person's symptoms, relationships or response to treatment.
Consent and governance still apply to donor-derived cells, genomic data, storage and future reuse. Making the cells in a laboratory does not remove these duties.