The Process

Types of Xenotransplantation

-Solid Organ: A procedure in which an animal organ, such as kidney or liver, is transplanted into a human.

-Cell and Tissue: The transplantation of tissues and cells from an animal without surgical connection of any animal blood vessels to the recipient’s vessels.

-Extracorporeal Perfusion: Occurs when human blood is circulated outside of the body through an animal organ, such as a liver or a kidney, or through a bioartificial organ produced by culturing animal cells on an artificial matrix.

-Exposure to Living Animal-Derived Material: A procedure in which human bodily fluids, cells, tissues or organs are removed from the body, come into contact with animal cells, tissues or organs and are then placed back into a human patient.

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Immunologic Barriers of Xenotransplantation

Xenograft Rejection

Hyper Acute Rejection

This dramatic immunologic reaction, antibodies circulating in human blood bind to the vascular epithelium of the animal organ and trigger a cascade that quickly results in thrombosis, of the graft.

Humans have antibodies known as xenoreactive natural antibodies (XNAs) directed against nonprimate species. Pigs contain the carbohydrates Gal1 and 3a-GalbGlcNAC-R and the human body perceives them as antibodies and attack the pig cells.

The immunologic cascades triggered destroy xenografts within minutes to hours causing engorgement and discoloration of the organ. Under light microscopes, hemmorrhages are evident. Mast cells begin to release histomine as well, causing platelet degranulation.

-Thrombosis is a blood clot inside of a blood vessel.

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Acute Vascular Rejection

If the transplanted organ is not rejected within minutes to hours, a more delayed type of immunologic response leads to thrombosis of the graft within hours to days.
Under light microscopes, hemmorrages and widespread coagulation of microvasculature are observed. There is an infiltration of monocytes and natural killer cells over several days. Also, cytokine expression, platelet deposition and very small numbers of T-cells are noted.

Endothelial cell activiation is believed to play a key role, though it is a type II activation because it involves gene induction and protein synthesis. This includes a shift to a procoagulant state, secretion of chemokines such as protein-1 and induction of leukocyte adhesion molecules.

-A xenograft is another name for the organ or tissue transplanted during xenotransplantation.

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