Regenerative medicine strategies Flashcards
What problems and solutions do ES cells have
ESC can differentiate into multiple cell types and can reconstitute whole tissue
Very difficult to direct ES cell behaviour once they have been
transplanted.
- Once transplanted, ESC respond to signals from environment
• Signalling pathways have different functions during early development compared to adult
Ø ESC transplanted into the kidney capsule give rise to tumours (tetracarcinomas) composed cells from all tissues of adult
What problems and solutions adult stem cells have
- Lineage restricted , overcome limitations of ES cells
- Self renew so can maintain tissue indefinitely
- Possess risk for development of tumours
- Many degenerative diseases affect tissues that do not have proper stem cells
What problems and solutions terminally differentiated cells have
- Do not divide so unlikely will drive tumour formation
- Much larger number of cells has to be transplanted
- Many mature cell types fail to integrate once introduced into new environment
What problems and solutions progenitors have
- Lineage restricted cells that can readily differentiate
- Become extinguished early post-natal development
Only capable of a finite number of divisions
Why is single cell transplant limiting ?
surrounding cells may become affected
limitations of transplanting an organ
organs coming from donor and recipient must be immunosuppressed and might be take immunosuppressive drugs
also there are limited number of organs available
Why should we transplant engineered tissues
- Tissues consist of multiple cell types as well as non-cellular scaffold and can be lost during damage and disease
- Can generate all required cell types ex vivo and assemble to form the whole organ
- Make from patients own stem cells or select from large stem cell bank
How to regenerate skin
isolate cells from skin grafts and expand them into sheets and transplant back onto patients
Describe personalised medicine using pluripotent stem cells
it can be expanded indefinitely, can generate induced iPSCs from individual patients so cells would be autologous. Also can genetic engineer cells towards desired cell type but hard to control when gene is expressed
What should be aware of when differentiating iPSCs into mature or progenitor cells
generate cells that are pure, safe and at the right stage.
Pure means to avoid undifferentiated cells within the culture. Safe is not to gain any new mutations that make them cancerous or dysfunctional
At the right stage so they are mature enough
How to get whole tissues from iPSCs
- Synthesize some sort of artificial scaffold
- To be able to differentiate iPSCs into all cells of the tissue and get cells to occupy the right positions- Organoids
- Organ-like structures that self-organise in culture to resemble the tissue from which they are derived
- Organoids
What are the advantages and limitations when using tissue stem cells in personalised medicine
dvantage
- Safe than transferring iPS or ES cell-derived tissues
- No risk of remaining undifferentiated cells causing teratomas
- Organoids can be transplanted at site for damage from a number of tissues such as gut, lung, kidney and liver
• Some organoid cultures resemble their tissue of origin better than others
Limitations
- Ability to culture and expand tissue stem cells in a dish - Structures left with little control over size or topology -> very heterogenous cultures
What can we obtain when we reprogram cells to iPCs for alzheimers
investigate role of mutated proteins during normal neuronal development
Look at how formation of AB plagues and neurofibrillary tangles affect cells leading to cell death
study early markers or indicators of disease
design and test drugs that stop the disease or counteract the toxicity
organdie can investigate disease progression in 3D
