Xenotransplantation involves transplanting cells, tissues or organs from animals to humans to address the shortage of human donor organs. The first type attempted was concordant xenotransplantation using organs from primates similar to humans. However, discordant xenotransplantation using organs from pigs is more promising due to similarities in organ size and physiology. Major barriers to xenotransplantation success are hyperacute rejection within minutes due to pre-existing antibodies, acute vascular rejection within days or weeks, and cellular rejection as T-cells recognize the foreign antigens. Strategies to overcome these barriers include genetically modifying pigs to eliminate antigen triggers, depleting antibodies in recipients, and inducing donor-specific tolerance through bone marrow chimerism. Another

1. XENOTRANSPLANTATION

2. CONCEPT
Xenotransplantation is
the transplantation of
cells, tissues or organs
from one species to
another, particularly
transplants from animals
to humans.
It was formulated to
overcome the shortage
of donor organs.

3. HISTORY

5. TYPES OF XENOTRANSPLANTATION
SOLID
ORGAN
XENOTRA
NSPLANT
CELLULAR
HUMAN/A
/TISSUE
NIMAL TYPES XENOTRA
HYBRID
NSPLANT
EXTERNAL
THERAPIES

6. CHOOSING THE DONOR SPECIES
TYPE BETWEEN EXAMPLE
CONCORDANT Closely
related/si Baboon Human
milar
species
DISCORDANT Distantly
related/ Pig Human
dissimilar
species

7. TRANSPLANTATION
REJECTION;IMMUNOLOGICAL
BARRIERS
1.Hyperacute xenograft rejection,HXR
2.Cellular xenograft rejection,
3.Acute vascular xenograft rejection,ACXR
4.Chronic xenograft rejection,

8. 1.Hyperacute xenograft rejection,HXR

9. OVERCOMING HYPERACUTE REJECTION
•alter the organ source through using genetically engineered
pigs (e.g., pigs that will lack the α-Gal epitope and/or will have
an artificially added gene[s] for human complement-regulatory
proteins (such as decay-accelerating factor)
• alter the recipient by depleting naturally occurring
antibodies directed against α-Gal (NXAs) prior to xenograft
receipt. Either approach to overcoming HAR may also
facilitate the potential for the human recipient to be infected
by endogenous retroviruses from the pig xenotransplantation
product.

10. 2.Acute vascular xenograft rejection,ACXR

11. OVERCOMING ACUTE VASCULAR REJECTION
•Administering a synthetic thrombin inhibitor to modulate
thrombogenesis
•Depletion of anti-galactose antibodies (XNAs) by
techniques such as immunoadsorption, to prevent
endothelial cell activation
•Inhibiting activation of macrophages (stimulated by
CD4+ T cells) and NK cells (stimulated by the release of
Il-2). Thus, the role of MHC molecules and T cell
responses in activation would have to be reassessed for
each species combo.

12. 3.Cellular xenograft rejection,

13. A proposed strategy to avoid cellular rejection is to induce donor
non-responsiveness using hematopoietic chimerism. Donor stem
cells are introduced into the bone marrow of the recipient, where
they coexist with the recipient’s stem cells. The bone marrow stem
cells give rise to cells of all hematopoietic lineages, through the
process of hematopoiesis. Lymphoid progenitor cells are created by
this process and move to the thymus where negative selection
eliminates T cells found to be reactive to self. The existence of
donor stem cells in the recipient’s bone marrow causes donor
reactive T cells to be considered self and undergo apoptosis.

14. 4.Chronic xenograft rejection,

15. One concern raised about xenotransplantation
is the risk of inadvertent transmission of
infectious agents into xenotransplant recipients
and subsequent secondary transmission of
infections to the wider human population. This
risk is an important obstacle to the use of this
technology. The potential for secondary
transmission of infections makes the risk of
xenozoonoses a global issue.
XENOZOONOTIC DISEASE RISK AND PREVENTION ISSUES

16. "O Adam! shall I lead thee to the
Tree of Eternity and to a kingship
that never decays?" (20:120). Satan
also said "I will mislead them, and I
will create in them false desires; I
will order them to have (in
abundance) the animals' ears cut
(from the origin), and I will order
them to change Allah's creation"
(4:119).

17. THANK YOU !