Transplantation 2 Flashcards
what transplant was successfully performed last january
the first ever porcine to human heart
transplant - obtained from a genetically engineered pig
3 disadvantages of xenografting with primates even though they’re concordant
endangered
ethical concerns
retrovirus
2 disadvantages of xenografting with monkeys even though they’re concordant
small size
retrovirus
2 disadvantages of xenografting with cow/horse/sheep
dis concordant
large size
2 reasons why xenografting with dog would be bad
dis concordant
ethical concerns
2 advantages of xenografting with pig, although requires genetic engineering
partly concordant
size- compatible
what must be performed in xenografting to avoid rejection
genetic modification
2 key genetic modifications to date
knock out porcine carbohydrate genes (GAL)
induce expression of human complement and coagulation regulatory molecules
2 key genetic modifications to date
knock out porcine carbohydrate genes (GAL)
induce expression of human complement and coagulation regulatory molecules
what is Donation after Circulatory Death
the retrieval of organs
from patients whose death is diagnosed and confirmed using cardiorespiratory criteria
2 types of Donation after Circulatory Death (DCD)
Controlled
Uncontrolled
when does controlled DCD take place
after death caused by planned withdrawal of life-sustaining treatments
what is uncontrolled DCD
organ retrieval after a unexpected cardiac arrest, from which the patient cannot or should not be
resuscitated.
how many organs are donated after circulatory death
40%
islet cell transplant process
- donor pancreas
- Ricordi chamber - key islet isolation device
- separated islets
- islets introduced into the liver of recipient
- transplanted islets secreting insulin in liver
what do islet cells produce in the pancreas
insulin
4 advantages of islet transplants
Can remove the need for insulin
injection
Prevents hypos
Improves overnight control
Transplant surgery is easy, quick and minimally invasive
Potential for xenotransplantation
3 limitations of islet transplantation
Only 2% of the donor pancreas is islet material
Repeated transplants often necessary
Shortage of donors
Immunosuppression
required – side effects
3 sites for islet transplantation for diabetes treatment
the anterior chamber of the eye
spleen
bone marrow
kidney capsule
subcutaneous space
what cells are involved in the future of islet transplantation
induced pluripotent stem cells
what is Bone marrow transplantation
the transfer of bone marrow cells from
one human to another
what can bone marrow transplantation be used to treat
leukaemia
immunodeficiency or anaemias
how many BMTs are over 350,000 centres in europe performing a year
more than 20,000
whats a serious complication of BMTs
graft-versus-host disease
how can HSC reconstitute damaged bone marrow
if they are harvested from cultures derived from bone marrow cells and are re-infused
whats the chance of match for stem cells for transplant from matched sibling
25%
whats the chance of match for stem cells for transplant from matched unrelated donor
50%
what has restricted availability but better outcomes than matched unrelated donor and less graft-versus-host disease
stem cells from umbilical cord blood
whats autologous HSCT
transplanted stem cells
previously taken from the patient (bone marrow/peripheral blood stem cells)
why is autologous HSCT less complicated
as it is MHC compatible
what does autologous HSCT allow for pre-transplantation, which will irreversibly damage bone marrow
high dose chemo and radiotherapy
7 steps of autologous HSCT
- Mobilise stem cells using growth factor and chemotherapy
- stem cells collected from peripheral blood
- stem cells frozen until required
- conditioning chemotherapy to suppress IS
- stem cells thawed and re-infused
- support with blood products and antibiotics (2 weeks)
- Further follow-up as outpatient for 2-3 months with regular blood tests and medication
how does collection differ with cord blood vs bone marrow
cord blood- collection is non-invasive, painless and poses no risk to the donor
Bone marrow - collection is invasive and painful, and must be performed in hospital surgery
why is GVHD reduced to 10% with cord blood
due to absence of antibodies in stem cells
why does it require grater HLA match to perform a transplant with bone marrow compared to cord blood
due to maturity of stem cells
is cord blood or bone marrow less expensive
cord blood
how much out of all unrelated bone marrow transplants does serious GVHD occur in
60%
when does GVHD occur
when immune cells from the donor (largely T-cells), attach the
recipient’s tissues
When does graft vs leukaemia effect occur (often simultaneously with GVHD)
when immune
cells from the donor
(largely Tcells), eliminate residual
leukaemia cells in the
recipient
what must be measured post-transplant for indicate outcome
level of engraftment
for malignancies, how much donor engraftment is required to prevent relapse
100%
what may be enough to correct anaemias and enzyme deficiencies
mixed chimerism
how is chimerism most often measured for analysis
STR analysis (short tandem repeat)
