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Xenotransplantation

How it Works

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How it Works
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How is this process possible?

Deoxyribonucleic acid from a human is mixed with that of a pig, so the pig inherits human DNA. There is not enough DNA present to create a new species, but there is enough to allow the pigs' organs to be transplanted without risk of rejection.

A female pig is given increased amounts of hormone to cause her to ovulate and produce more eggs than usual. She mates with a male and before the DNA from the sperm can fuse with the DNA from her egg, the fertilized eggs, are removed from her oviduct. The embryos are injected with a solution containing a small amount of human DNA. Since the zygotes are only exposed to a small amount of DNA, not all of the eggs will inherit the genes. Only a small percentage of the resulting pigs will become transgenic. However, transgenic pigs can be bred with other transgenic pigs to reproduce, 50% of the offspring will also be transgenic. Pigs have 100 000 to 200 000 genes only 1% will be human DNA. Once the pig has grown to full size, the needed organs will be surgically removed before the pig is put down.

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http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/images/dna.gif

The reason why the pig embryos have to be injected with human DNA is so that once the organ has been transplanted, the human body does not reject the organ. The human body must recognize the transplanted tissue as its own. If the human body does not recognize the tisse, it will be considered alien and foreign and the body will go into what is known as hyperacute rejection. The part of the tissue which is recognised by the human is on the surface of the cells, these are called antigens. Antigens are what the organ is marked with and if it is a foreign organ, the body will create an immune response. Antibodies present in humans bond with the antigens of a foreign organ. Once they have bonded, the organ is recognixed as an alien tissue and is attacked. The organ is attacked by the complement protein system made up of approximately 24 different proteins. The complement protein system targets the lining of the tissue's blood vessels. The membranes of the blood vessels are eventually broken down and they are no longer capable of supplying blood and therefore oxygen to the invading tissue.

Specific (regulatory) proteins in the cell stops the body's immune system from destroying existing organs already present in the human body. The is because they restrain the complementary protein system attacking.

The human DNA that is injected into the pig embryo contains the five regulatory proteins which help restrain the response from the complemetary protein system. These proteins are called: CD46, CD55, CD59, decay accelerating factor (DAF) and H-transferase. The only role of these proteins is to make themselves recognizeable to the body. CD46, CD55, CD59 and DAF all code for the production of the inhibitors of the complementary protein system. H-transferase is responsible for the production of an enzyme. This enzyme works against the effects of the antigen on pigs cells that would cause the complementary protein attack. The H-transferase produces the epitope which is present on human cells. The human epitope is said to dominate over the pig epitope and will be recognized over the pig epitope. The cells in the pig's body will have high levels of the human epitope and therfore, once the pig's organ is transplanted into the human body, the human will not experience an imune response to the foreign tissue.