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XENOTRANSPLANTATION
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.
HISTORY
TYPES OF XENOTRANSPLANTATION
               SOLID
               ORGAN
              XENOTRA
              NSPLANT




                          CELLULAR
    HUMAN/A
                           /TISSUE
     NIMAL     TYPES      XENOTRA
     HYBRID
                          NSPLANT




              EXTERNAL
              THERAPIES
CHOOSING THE DONOR SPECIES
TYPE         BETWEEN EXAMPLE


CONCORDANT   Closely
             related/si   Baboon     Human
             milar
             species




DISCORDANT   Distantly
             related/          Pig     Human
             dissimilar
             species
TRANSPLANTATION
REJECTION;IMMUNOLOGICAL
        BARRIERS

   1.Hyperacute xenograft rejection,HXR


         2.Cellular xenograft rejection,


    3.Acute vascular xenograft rejection,ACXR



        4.Chronic xenograft rejection,
1.Hyperacute xenograft rejection,HXR
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.
2.Acute vascular xenograft rejection,ACXR
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.
3.Cellular xenograft rejection,
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.
4.Chronic xenograft rejection,
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
"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).
THANK YOU !

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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.
  • 4.
  • 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,
  • 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.
  • 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.
  • 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).