Differences in terms of regenerative medicine and tissue engineering?
Regenerative medicine is an umbrella term including tissue engineering, but not exclusively e.g. cell based therapies may involve no TE, whereas TE of food does not come under regnerative medicine etc
Why the need to TE food?
- UNSUSTAINABLE FOOD PRODUCTION.
- Water useage of agriculture 70%, 37% of landmass (besides antarctica) is agriculture, and worse for greenhouse gases than whole of transport sector.
- Worldwide meat production is increasing, and the population is increasing.
- Predicted 69% increase in food calories needed from 2006 to 2050.
- animals in confined spaces- Antibiotic resistance
- Ethics- growing animals just for slaughter and use of the most basic tissues.
- Space missions
Who famously proposed TE early of animals for food?
1930s churchill said the absurdity of growing chickens just to eat their breast or wing, and that in the next 50 years we would just grow that part.
Example of lab grown tissue?
Lab grown burger 2013. Grew the skeletal muscle.
about lab grown burger
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How does muscle regenerate/grow?
- Injury activates satellite cells (muscle specific precursor stem cells). (Notch and Wnt signalling sometime)
- Satellites proliferate.
- Satellites differentiate into a myoblast.
- Myoblasts fuse into myotubules
- Mature into myofibers. (MyoD, myogenin etc)
Basic how would lab meat be grown? (4)
- Biopsy taken from animal,
- isolated satellite cells,
- culture- proliferative phase,
- differentiation phase. Into myoblasts, fuse to myotubules and then mature to myofibers.
Disadvantage of satellite cells for lab grown food? Instead?
They cannot proliferate indefinitely. Can increase in numbers 50-70%, so need to source a lot of cells- still taking biopsies from animals- causing them harm.
Properties biomaterial scaffold for meat should have?
Digestible, non-allergenic non-toxic, not have bad taste/texture, support the satellites maturation and differentiation
Biorectors for food growth?
One study put myoblasts onto pourous collagen microspheres and put into bioreactors. BUt muscles need some sort of anchorage and have mechanical and electrical stimulation within the bioreactor.
How could muscle tissue be created into a more organised structure?
3d Printing muscle tissue. E.g. make a finer texture like a steak
Difference between regenerative medicine and food TE manufacture?
Medicine- Mainly academia research- complete transparency of protocols etc,
Food- private companies- commercial- don’t publish their protocols all patterned etc- so hinders progress.
Also Public acceptance bigger issue.
Scale of food production?
Would have to be huge- calculation of 1 bioreactor for every 10 people- environmental footprint large and huge volume of media needed.
Advantages of TE meat over animal?
- Ethics
- Sustainability?
- Control over taste/flavour
- Healthier- add vitamins, reduce fat etc.
- New range of products- more exotic animals?
TE Leather production how?
- Take skin sample from animal
- isolate and multiply cells.
- deposit onto sheets and induce collagen production
- Layer sheetds and fuse layers into a solid hyde.
- Treatment- Tan, dye etc.
TE Leather vegan?
“modern meadow” now changed to produce vegan leather from yeast or bacteria.
Key Historical events that have shaped the regulation of medicines?
‘Elixir Sulfanilamide’ incident 1930’s- Drug for staphylococcus infection- dissolved in antifreeze. 4/100 children died in trial.
The Nuremberg Code-Tested on prisoners during WWII- then law came out that an testing should be on informed and voluntary people.
The thalidomide incident 1950’s: Noted need to not only test short term effects but also long term safety.
DECLARATION OF HELSINKI 1964. Statement of ethical principles for medical research.
GOOD CLINICAL PRACTICE- have to prove efficacy and safety on animals and have well trained staff with reproducible protocols.
Problem with regulation of TE products?
It doesnt fall within the relms of medicinal products or medical devices but between the two. Cell therapy and gene therapy also between, so new regulation was needed “advanced therapies” under EU regulation. Require case- by- case consideration- not set trials.
major concerns with using cells in TE products?
Cancerous e.g. EB boy. Unpredictable as living cells evolve (Epigenetic changes), migrate (different environmental cues here?) and interact with other cells.
3 Things advanced therapies need by EU regulation?
- Establishment of maufacting process and controls (robust and reliable) E.g. Age related macular degeneration protocol have to say the QC steps for each step. E.g check cell appearance, Karyotype (tumourgenic) cell counts, sterilise etc
- Pre-clinical safety and efficacy in relevent models.
- Clinical trials in human participants (involve surgery so only can give to patients really- ‘one off compassionate treatments’)
Choice of animal models for Advanced therapies?
Just have to use the most appropriate model. E.g. mice good as small and cheap but depends what for as their cartilage regenrates better than ours for example, so horse may be more suitable. E.g. cats often for cochlea implants similar strucutre, not minute.
4 things basic to consider for TE constructs?
Safety, engraftment (e.g. vascularisation), functionality and immune response
Things to consider in trial for advanced therapies which may be different to normal medicinal products?
- Small exploratory trial on small number of patients- unethicial to do surgery on healthy inviduals.
- Means not blinded as patient knows whether had surgery or not.
- Surgery often depends on how good the surgeon is, comparison may be difficult.
- Can standardise though to an extent- ensure patients got same thing wrong and same check ups and aftercare etc, but the wound may vary and patients responses.
- Defining the competitor- drugs are often put in comparison to the current drug treatment but this may not be possible as may not be an alternative.
- Dosing- not if construct, but if cells involved- how many?
Challenges of commercialisation of medicinal products compared to shop items etc?
Unlike in shop where customer decides whether to buy something, its the government (NHS) that pays so balancing act of cost budgetting. Dependant upon politics.
Risk benefit assesment by doctor. Can give one off compassionate treatment of advanced therapies (Hospital exeption) if desperate etc.
