ORGAN TRANSPLANTATION

Geeta Mohan
Organ transplantation

• Organ transplantation is the moving of an organ from

one body to another or from a donor site to another
location on the person's own body, to replace the
recipient's damaged or absent organ.
• The first successful transplantation operation was a
kidney transplanted between identical twins by Joseph
Murray , it was performed at Boston in 1954
• Organs and/or tissues that are transplanted within the
same person's body are called autografts. Transplants
that are performed between two subjects of the same
species are called allografts.
• Allografts can either be from a living or cadaveric
source.
 Organ transplantation

• Organs that can be transplanted are

the heart, kidneys, liver, lungs, pancreas, intestine,
and thymus. Some organs, like the brain, cannot be
transplanted. Tissues include bones, tendons (both
referred to as musculoskeletal
grafts), cornea, skin, heart valves, nerves and veins.
• Worldwide, the kidneys are the most commonly
transplanted organs, followed by the liver and then
the heart
• Cornea and musculoskeletal grafts are the most
commonly transplanted tissues , these outnumber
organ transplants by more than tenfold.
Organ transplantation

• Organ donors may be living, brain dead, or dead via

circulatory death . Tissue may be recovered from donors
who die of circulatory death, as well as of brain death – up
to 24 hours past the cessation of heartbeat. Unlike organs,
most tissues (with the exception of corneas) can be
preserved and stored for up to five years.
• Transplantation raises a number of bioethical issues,
including the definition of death, when and how consent
should be given for an organ to be transplanted, and
payment for organs for transplantation
• Transplantation medicine is one of the most challenging
and complex areas of modern medicine. Some of the key
areas for medical management are the problems
of transplant rejection
• Survival rates after both liver and heart transplantation
remained low until the introduction of cyclosporine in 1980.
This drug, in combination with existing less effective
immunosuppressive drugs, markedly increased survival
rates and led to rapid expansion of the organ
transplantation field
 Types of transplant

• Autograft and autotransplantation

• Allograft and allotransplantation
• Isograft
• Xenograft and xenotransplantation
• Domino transplants
Autograft
• Autografts are the transplant of tissue to the same
person. Sometimes this is done with surplus tissue,
tissue that can regenerate, or tissues more desperately
needed elsewhere (examples include skin grafts, vein
extraction for CABG (Coronary artery bypass graft ), etc
• Sometimes an autograft is done to remove the tissue
and then treat it before returning it to the person
(examples include stem cell autograft and storing blood
in advance of surgery).
• In a rotationplasty, which is a type of autograft wherein
a portion of a limb is removed, while the remaining limb
below the involved portion is rotated and reattached.
This procedure is used when a portion of an extremity is
injured or involved with a disease, such as cancer. The
limb is rotated because the ankle flexes in the opposite
direction compared to the knee. The benefit to the
patient is that they have a functioning knee joint and
can run and jump.
CABG
Rotationplasty
Allograft
• An allograft is a transplant of an organ or tissue
between two genetically non-identical members of
the same species.
• Most human tissue and organ transplants are
allografts.
• Due to the genetic difference between the organ and
the recipient, the recipient's immune system will
identify the organ as foreign and attempt to destroy
it, causing transplant rejection
• The risk of transplant rejection can be estimated by
measuring the Panel reactive antibody level and HLA
typing.
Isograft
Isograft : A subset of allografts in which organs or
tissues are transplanted from a donor to a
genetically identical recipient (such as an identical
twin).
Isografts are differentiated from other types of
transplants because while they are anatomically
identical to allografts, they do not trigger an immune
response.
Xenograft
• Xenograft : A transplant of organs or tissue from one
species to another.
• Bioprosthetic valves are usually made from animal tissue
(xenograft) mounted on a metal or polymer support.
• An example is porcine (pig) heart valve transplant, which
is quite common and successful.
• Another example is attempted piscine-primate (fish to
non-human primate) transplant of islet (i.e. pancreatic
tissue)
• The latter research study was intended to pave the way
for potential human use , if successful.
• However, xeno transplantion is often an extremely
dangerous type of transplant because of the increased
risk of non-compatibility, rejection, and disease
Xenograft
Xenograft
Domino transplants
• In people with cystic fibrosis, where both lungs need to
be replaced, it is a technically easier operation with a
higher rate of success to replace both the heart and
lungs of the recipient with those of the donor. As the
recipient's original heart is usually healthy, it can then
be transplanted into a second recipient in need of a
heart transplant
• This term also refers to a series of living donor
transplants in which one donor donates to the highest
recipient on the waiting list and the transplant center
utilizes that donation to facilitate multiple transplants.
These other transplants are otherwise impossible due
to blood type or antibody barriers to transplantation.
The "Good Samaritan" kidney is transplanted into one of
the other recipients, whose donor in turn donates his or
her kidney to an unrelated recipient.
Cystic fibrosis
ABO-incompatible transplants

• ABO-incompatible transplants - Because very

young children (generally under 12 months, but
often as old as 24 months ) do not have a well-
developed immune system it is possible for them to
receive organs from otherwise incompatible
donors. This is known as ABO-incompatible (ABOi)
transplantation.
• Graft survival and people’s mortality is
approximately the same between ABOi and ABO-
compatible (ABOc) recipients. While focus has been
on infant heart transplants, the principles generally
apply to other forms of solid organ transplantation .
Transplantation in obese individuals
• Until recently, people labeled as obese were not
considered appropriate candidates for renal
transplantation. In 2009, the physicians at
the University of Illinois Medical Center performed
the first robotic kidney transplantation in an obese
recipient and have continued to transplant people
with Body Mass Index (BMI)’s over 35 using robotic
surgery.
• As of January 2014, over 100 people that would
otherwise be turned down because of their weight
have successfully been transplanted.
 Organs and tissues transplanted

Chest
• Heart (deceased-donor only)
• Lung (deceased-donor and living-related lung transplantation)
• Heart/Lung (deceased-donor and domino transplant)
• Abdomen
• Kidney (deceased-donor and living-donor)
• Liver (deceased-donor and living-donor)
• Pancreas (deceased-donor only)
• Intestine (deceased-donor and living-donor)
• Stomach (deceased-donor only)
• Testis(deceased-donor and living-donor)
 Organs and tissues transplanted
Tissues, cells and fluids
• Hand (deceased-donor only),
• Cornea (deceased-donor only)
• Skin, including face replant (autograft) and face
transplant (extremely rare)
• Islets of Langerhans (pancreas islet cells) (deceased-
donor and living-donor)
• Bone marrow/Adult stem cell (living-donor and autograft)
• Blood transfusion/Blood Parts Transfusion (living-donor
and autograft)
• Blood Vessels (autograft and deceased-donor)
• Heart Valve (deceased-donor, living-donor and xenograft
[porcine/bovine])
• Bone (deceased-donor and living-donor)
Types of donor

• Organ donors may be living or may have died of brain

death or circulatory death. Most deceased donors are
those who have been pronounced brain dead. Brain dead
means the cessation of brain function, typically after
receiving an injury (either traumatic or pathological) to the
brain, or otherwise cutting off blood circulation to the
brain (drowning, suffocation, etc.). Breathing is maintained
via artificial sources, which, in turn, maintains heartbeat.
• Tissues may be recovered from donors up to 24 hours past
the cessation of heartbeat. In contrast to organs, most
tissues (with the exception of corneas) can be preserved
and stored for up to five years
Living donor

• In living donors, the donor remains alive and

donates a renewable tissue, cell, or fluid (e.g.,
blood, skin), or donates an organ or part of an
organ in which the remaining organ can regenerate
or take on the workload of the rest of the organ
(primarily single kidney donation, partial donation
of liver, lung lobe, small bowel).
• Regenerative medicine may one day allow for
laboratory-grown organs, using person's own cells
via stem cells, or healthy cells extracted from the
failing organs.
Deceased donor

Deceased donors (formerly cadaveric) are people

who have been declared brain-dead and whose
organs are kept viable by ventilators or other
mechanical mechanisms until they can be excised
for transplantation
There is increasing use of donation after circulatory-
death-donors (formerly non-heart-beating donors)
 The steps involved in transplantation

• The first round of tests involves blood typing to see

if both the donor and the recipient belong to the
same blood type. The blood tests are simple and it
involves using antisera. The blood is checked for the
A and B antigens and also for the Rh factor
• The second round of tests involves the matching of
tissues. This is called the HLA Typing (HLA stands
for Human leucocyte antigen )
HLA Typing

• Everyone has several antigen located on the surface

of their leucocytes
• One particular type of antigen is HLA (Human
Leucocyte Antigen ) which is responsible for
stimulating the immune response to recognize tissue
as self or non self
• It is controlled by a set of genes located next to each
other on Chromosome 6, called MHC (major
histocompatibility complex )
• Every person inherits one each of the antigen sets
from both the parents
HLA matching
• HLA are proteins—or markers—on most cells in your body. HLA
stands for human leukocyte antigens.
• HLA matching is used to match patients and donors for blood or
marrow transplants. It’s much more complicated than blood typing.
For HLA matching:
• You and potential donors will have blood drawn
• The blood is tested in a lab to figure out your HLA type
• Your HLA will be compared to potential donors to see if there is a
match
• There are many HLA markers. Each HLA marker has a name. The
names are letters or combinations of letters and numbers.
• Sometimes, it’s hard to find a match because some HLA types are
less common. HLA types are inherited so siblings can sometimes be
a match for each other.
• Each of your brothers and sisters who has the same parents as you
has a 1 in 4 chance (25%) of being a complete, or full, match. You’re
more likely to match someone with a similar ethnic background or
ancestry.
 HLA Test
• HLA stands for Human leucocyte antigen that is produced by
the major histocompatibility complex or MHC.
• The test is micro cytotoxicity test. It is a simple procedure :-
• The WBCs from potential donors (A and B) and the recipient
(R) are distributed in a series of wells separately on a micro
titre plate.
• Antibodies specific for class I and class II MHC antigens are
added to the wells.
• After incubation, complement (usually rabbit serum ) is added
to the wells.
(The three major roles of complement are:
• promoting acute inflammation process that allow white cells and macrophages to
migrate to the source of the problem
• altering the cell surfaces to encourage phagocytosis
• modifying the cell surface that will eventually lead to cell lysis)
• Next a dye (usually a flurochrome – Ethidium bromide or
Eosine –Y) is added to find out if there is a cytotoxic reaction.
HLA Typing

• If the specific antigen is present on the cell the

antibody will bind, and if there is a cytotoxicity
reaction , it activates the complement which
damages the cell membrane by punching holes
making it porous and permeable to the vital stain
added and the cells become stained
• If cells in the micro titre wells that are stained are
similar in the case of the donor and the recipient then
the tissues are similar or they are matching. For
example the donor ‘A’ and the recipient ‘R’ shows the
stained cells in the same number of wells. The donor
B shows reactions in different wells. Thus the tissues
of the donor ‘B’ do not match with the recipient.
Human leucocyte antigen test

• Donor A

• Donor B

• Recipient

Donor A matches with the recipient

HLA matching
 The steps involved in transplantation
Another test to identify the class II antigen between a
potential donor and the recipient is as follows,
• The lymphocytes of the donor are irradiated or treated
with anti mitotic chemicals so that the cells do not
divide.
• These lymphocytes are added to the recipient’s WBC. If
the MHC class II antigens are different the recipient’s
cells will divide rapidly and take up large quantities of
radioactive nucleotides. The amount of radioactive
nucleotide taken up by the recipient will be directly
proportional to the MHC class II differences between the
donor and the recipient.
• If the class II antigens are similar the recipient’s cells
will remain as such and there will be no reaction.
Immunosuppressors

Differences in the minor histocompatibility gene can

be handled with immunosuppressors.
The natural immune response against any foreign
tissue can be suppressed by various methods :
I. Use of radiation : X-rays is used to irradiate the
recipient so that the lymphocytes are eliminated in
the recipient just before grafting.
The treatment where the lymph nodes, the spleen and
the thymus are exposed to X rays is called total
lymphoid irradiation. The recipient is exposed to a
minimum dose of X-rays daily for several weeks till he
is exposed to a sufficient dose of 3400 rads totally.
The X-rays would have destroyed the existing
lymphocytes
Immunosuppressors

II . Chemotherapy : The use of chemicals or drugs for patients

who have undergone an organ transplant to manage graft
rejection and cause immune suppression is called chemotherapy.
The drugs used prevent the cells of the immune system from
dividing. The drugs commonly used are classified into various
categories such as :
a .Mitotic inhibitors such as, Azathioprine and cyclo phoshamide
These drugs inhibit cell division and therefore they do not allow
the division of B and T cells.
b. Anti –inflammatory drugs such as, corticosteroids. The
corticosteroids that are derived from cholesterol are regularly
used as anti-inflammatory drugs. The drugs have the property of
reducing the number of B cells and T cells. They also reduce the
activity of these cells.
c. Fungal metabolites such as, Cyclosporin A and tacrolimus
prevent activation of T cells.
 Immunosuppressors

III .The Use of Monoclonal Antibodies The use of

monoclonal antibodies against the surface molecules of the
T cells and B cells reduces their population sufficiently to
cause immuno suppression.
The antibodies coat the T cells. The T cells bind to the Fc
region of the phagocytes that then devours the T cells. This
causes depletion in the population of the activated T cells.
The use of chemicals and radiation has harmful side
effects.
The above mentioned immune suppressors are non-specific.
They provide a general immunosuppressive effect.