These act as signals when they bind to receptors called integrins on cells.
Mechanical cues— such as the stiffness of the ECM— affect the softness of the cells and let them take shape, rather than growing flat in two dimensions. Chemical cues trigger changes in gene expression and behaviour, telling cells to grow in a certain direction or differentiate into a specific type. There are specific growth factors for each tissue type, so because TSCs already carry some of their own proteins and growth factors, their growing process needs fewer additional ones.
Applications
After ESCs are extracted from an embryo, and iPSCs and TSCs from adult cells, the next major step is growing these stem cells into organoids inside an artificial extracellular matrix( ECM). Scientists commonly use Matrigel, which mimics the real ECM found in our organs and contains various proteins( such as laminin and collagen IV) and growth factors.
Because PSCs can mimic early human development, they are ideal for studying disease origins( such as kidney or heart defects during development), neuron behaviour( how networks form, and how disease and drugs disrupt activity or connections), and genetic disorders( by comparing healthy and mutated cells). They also drive regenerative medicine and cell replacement, especially for organs with low regeneration such as the brain, kidney and retina.
For example, apart from two small areas— the hippocampus and the sub-ventricular zone— there aren’ t many stem cells left after early development, so research relying only on TSCs would be limited.
Brain organoids made from PSCs can now recreate early versions of many more brain regions, with increasing complexity.
References
TSCs, meanwhile, naturally regenerate their own tissue type and retain the patient’ s unique mutations and traits, making them valuable for modelling adult diseases( such as intestinal organoids for inflammatory bowel disease), for personalised medicine and drug testing( testing chemotherapy sensitivity, reducing trial-and-error, and finding which drug works best on which mutation), and for clinical therapies( with a lower risk of immune rejection when the cells come from the patient themselves).
The gut, liver and airway are commonly used for TSC organoids. The gut, for instance, has high regeneration: many active stem cells and a strong ability to rebuild itself naturally, traits it keeps even after being placed into Matrigel. It even contains Lgr5 + adult stem cells, whose gene expression helps build the gut— working efficiently with Matrigel’ s proteins and growth factors.
Could we grow full organs for transplantation one day?
Hypothetically, yes— but blood vessels and micro-vasculature would need to be engineered and connected to the rest of the body to ensure full circulation, and bioreactors would be required to supply oxygen to the organ.
Ethical questions
First, the sourcing of ESCs is controversial, because the embryo must be destroyed during IVF to obtain them— which is why iPSCs( reprogrammed adult cells) are increasingly used instead. Second, there is ongoing debate over whether brain organoids could ever gain a form of consciousness, and whether that is a risk researchers should accept as the technology advances
Organoids are an innovative way of researching the human body without experimenting on real people— small in size, but huge in impact.
01 Review references compiled by the author on pluripotent and tissue-derived stem cells, Matrigel-based culture, and organoid applications in disease modelling and regenerative medicine.
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