lecture 21 Flashcards
xenotransplantation
How many cadaveric donors/solid organ transplants do we have compared to patients on the waiting list?
- 1998 - 2004: always much high numbers on the waiting list than transplants that occur
~ 1800 patients waiting for a transplant - 700 patients get transplants
- 200 cadaveric donors (this doesn’t match up)
- before about 1978 there wasn’t really a waiting list, ~ 500 translplants
- 1978 waiting list appears and increass exponentially
- number of transplants rises but plateaus
- 1978 was when the technique for immunosuppression was approved (cyclosporin?)
What are transplantation statistics?
- UK:
- ‘92 - ‘95 1700 transplants/year
- waiting list grew from 4,000 to 5,000
- USA:
- 45,000 patients waiting for transplants
- <6,000 cadaveric donors = 20,000 organs
no way for supply to meet the demand
~10-15% chance of dying while waiting for an organ, not unique to australia
Why do transplants?
costs
- dialysis $40,000
- kidney transplant $30,000 in first year
- $8,000 per year
improved quality of life
Why is there a shortage of donors?
- decrease in road accidents
- family permission less
- not suitable (age, disease, etc)
- time factor
- greater demand
What are possible solutions to this shortage?
- increase donors
- e.g. donor games
- getting older so not necessarily the solution
- artificial organs
- stem cells –> organs/tissue
- animal as donors: xenografts
- first transplantations were chimpanzee kidneys to human
What were patient attitudes towards xenografts?
131 renal patients:
- 51% would accept xenograft
- 39% unsure, wanted more information
- 10% unacceptable
Why did we revisit xenografts?
- molecular biology
- transgenesis/animal cloning
What are problems with xenografts?
- physiological
- ethical
- biological
- infection
- immunological
What are physiological problems of xenografts?
- size e.g. can’t use a mouse (too small) or a horse (too big), maybe a kangaroo? but we use sheep/pig
- complexity of function
e. g. sheep regulate insulin by glucose AND fatty acids –> not the same
What are ethical considerations of xenografts?
- emotional
- conservation
e.g. chimps etc are probably the best immunologically speaking, but people have issues with taking organs from this animal, cf pig
considerations for use of pigs:
- food (as long as people are willing to slaughter pigs for food, they should be able to be used for donating organs)
- insulin (major source of insulin for diabetics)
- heparin (anticoagulant)
- heart valves (used to replace broken valves in humans)
- breeding (a forerunner for genetic manipulation)
What are biological considerations of xenografts?
- adaptability to captivity
- pigs breed well in captivity
- primates breed poorly in captivity
- litter size
- pigs: 10
- primates: 1
- pig husbandry relatively easy
- gnotobiotic pigs available (germ designed/germ free)
What are infectious considerations of xenografts?
- primates: potential source of infection, especially viruses
- pigs: lower potential source for infection
- human viruses could infect primates, but not pigs
What are immunological problems associated with xenografts?
- hyperacute rejection: antibody causes immediate graft loss
- delayed xenograft rejection: macrophages/NK cells
- cell mediated rejection: T cells
What is hyperacute rejection?
- antibody
- antigen
- complement
- immediate
- clots
- loss of vascular endothelium
- haemmhorage and oedema
- not unique to xenografts
- e.g. mis-match blood transfusion
Do we have an ‘anti-pig’ antibody?
- yes: normal, present in all humans
- IgM, IgG, IgA
- 1-2% of all Ig
- > 95% to Gal-alpha (1,3) Gal
