Classification of grafts : The graft can be classified into four major types.

1. Autograft : The tissue of the original donor is grafted back into the same donor. For
example, skin graft from thigh to face in severely deformed case of burnt individuals
(plastic surgery).
2. Isograft : Graft between syngeneic individuals (ie., identical genetic constitutuion).
For example, clones or identical twins.
3. Allograft : (Homograft). Graft between allogenic individuals (ie., members of the
same species but of different genetic constitution. For example, kidney transplanted
from one human to another.
Xenotransplantation (heterograft) (xenos- from the Greek meaning "foreign"), is
the transplantation of living cells, tissues or organs from xenogenic individual (differnet
genetic linkage) to host. For example organ transplanted from pig to human, baboon to
human, Xenotransplantation of human tumor cells into immunocompromised mice. Such
cells, tissues or organs are called xenografts or xenotransplants.
Alexis Carrel is known as the founding father of experimental organ transplantation
because of his pioneering work with vascular techniques. Carrel and Guthrie contributed
substantially to the science of transplantation from 1904-1906. They performed
autogenous vein grafts, performed leg replantation in dogs, and developed the famous
patch-graft technique for widening narrowed vessels. They also performed heterotopic
experimental transplantation. Parts of a small dog were transplanted into the neck of a
larger dog. They developed the buttonhole technique for anastomosis of donor and
recipient vessels in kidney transplantation to prevent thrombus formation.
An American infant girl known as "Baby Fae" with hypoplastic left heart syndrome was
the first infant recipient of a xenotransplantation, when she received a baboon heart in
1984. The procedure was performed by Leonard L. Bailey. Fae died 21 days later due to
a humoral-based graft rejection thought to be caused mainly by an ABO blood type
mismatch, considered unavoidable due to the rarity of type O baboons.
Potential animal donors
Since they are the closest relatives to humans, non-human primates were first
considered as a potential organ source for xenotransplantation to humans.
Chimpanzees were originally considered the best option since their organs are of
similar size, and they have good blood type compatibility with humans, which
makes them potential candidates for xenotransfusions. However, since
chimpanzees are listed as an endangered species, other potential donors were
sought.
Baboons are more readily available, but impractical as potential donors. Problems
include their smaller body size, the infrequency of blood group O (the universal
donor), their long gestation period, and their typically small number of offspring. In
addition, a major problem with the use of nonhuman primates is the increased risk
of disease transmission, since they are so closely related to humans.[16]

 Pigs are currently thought to be the best candidates for organ donation. The risk
of cross-species disease transmission is decreased because of their increased
phylogenetic distance from humans. They are readily available, their organs are
anatomically comparable in size, and new infectious agents are less likely since
they have been in close contact with humans through domestication for many
generations. and the possibility of introducing new genes into the germline of the
pig. Current experiments in xenotransplantation most often use pigs as the donor,
and baboons as human models.
Significance & application
Human xenotransplantation offers a potential treatment for end-stage organ
failure. life-threatening and debilitating illnesses such
as cancer, diabetes, liver failure and Parkinson's disease
If vitrification can be perfected, it could allow for long-term storage of
xenogenic cells, tissues and organs so that they would be more readily
available for transplant.
Xenotransplantation of human tumor cells into immunocompromised mice is
a research technique frequently used in oncology research. [5] It is used to
predict the sensitivity of the transplanted tumor to various cancer
treatments.
Human organs have been transplanted into animals as a powerful research
technique for studying human biology without harming human patients
Xenotransplantation also is and has been a valuable tool used in research
laboratories to study developmental biology.

Genetic basis of organ transplants:

Success of organ transplants (i.e., Cornea, Kidney, Heart, Liver, Bone marrow) and
skin grafts depends on a proper matching of histocompatibility antigens that occur in all
cells of the body. Chromosome 6 of mouse contains a cluster of genes known as the
major histocompatibility complex (MHC), which in humans is called human
leukocyte antigen (HLA) complex. The alleles of HLA genes determine the
histocompatibility i.e., the compatibility between donor and recipient tissues in
transplants.
Graft rejection
To date no xenotransplantation trials have been entirely successful due to the many
obstacles arising from the response of the recipientsimmune system. This response,
which is generally more extreme than in allotransplantations, ultimately results in
rejection of the xenograft, and can in some cases result in the immediate death of the
recipient. There are several types of rejection organ xenografts are faced with, these
include:

Hyperacute rejection

Acute vascular rejection

Cellular rejection

Chronic rejection

Process of graft rejection : (Allograft)

When the graft or tissue involves two genetically distinct members of the same
species, graft rejection occurs because the antigens of the graft and host being different,
the immune response of the host rejects the graft. The graft dies, decays and is
eliminated from the host. The host also reacts to the graft and shows the following
symptoms.
1.Skin rashes,
2. Fluid accumulation in spleen and enlargement (Splenomegaly),
3. Emaciation (becoming thin),
4. Diarrhoea,
5. hepatomegaly,
6. Anaemia and general immune suppression,
7. Damage in bile ducts,
8. Increased bilirubin synthesis etc.
Both cell mediated and humoral immune responses follow in rejection. Sensitized T cells
(lymphocytes), macrophages, plasma cells are all involved in the primary or first set
rejection. In the secondary or second set reaction, B cells (B lymphocytes) and their
antibodies are involved. In the cell mediated reaction substances such as interleukin 1
(IL-1), Interleukin 2 (IL-2) etc take part. The final lysis of the graft is achieved by
lymphotoxins or TNF (Tumour necrosis factors) or proteolytic enzymes.
In clinical fields, graft rejection is prevented by : 1.Blood groups estimation (ABO
and Rh) in the host, 2. Testing the presence of cytotoxic antibodies in the host serum, 3.
Cross matching of tissues (Host Vs graft) prior to transplantation, 4. Giving
immunosuppressive drugs like cyclosporine and steroids etc to the host, 5. Total
lymphoid tissue irradiation etc.
In recent years, the cloning technology promises to bring solution to the problems
of graft or tissue rejection in transplantation surgery. By stem cell technology and cloning
of cells, organ culture is feasible. Organs cultured from the same embryo or individual
are safe and valuable for transplantation surgery.
Limitations
A continuing concern is that many animals, such as pigs, have a shorter lifespan
than humans, meaning that their tissues age at a quicker rate.
Host immune system lead to graft rejection
Disease transmission (xenozoonosis) and permanent alteration to the genetic code
of animals are also causes for concern.