Genetically Modified Pigs as a Temporary Transplant Source

Xenotransplantation, the transplantation of tissue from animals to humans, is a potential stepping stone technology to bridge the gap between today and a future in which all tissues can be grown to order from a patient's own cells. Xenotransplantation is not yet a completely practical possibility, as it has greater issues of immune rejection than transplantation between humans, but several lines of research are bringing it closer. One of these is decellularization, stripping cells to leave the scaffold of the extracellular matrix that is then repopulated with the recipient's own cells. Another is to genetically alter the donor animal to remove proteins that will trigger rejection:

[Researchers have] been investigating ways to allow the human body to accept organ and tissue transplants from animals. [The] team developed a strain of inbred miniature swine with organs that are close in size to those of adult humans. Since pig organs implanted into primates are rapidly rejected due to the presence of the Gal (alpha-1,3-galactose) molecule, [they] used the strain [to] generate miniature swine in which both copies of the gene encoding GalT (galactosyltransferase), the enzyme responsible for placing the Gal molecule on the cell surface, were knocked out.

When insufficient undamaged skin is available for grafting, tissue from deceased donors is used as a temporary covering. But deceased-donor skin grafts are in short supply and expensive - disadvantages also applying to artificial skin grafts - must be carefully tested for pathogens and are eventually rejected by a patient's immune system. Once a deceased-donor graft has been rejected, a patient's immune system will reject any subsequent deceased-donor grafts almost immediately.

When [the researchers] used skin from these Gal-free pigs to provide grafts covering burn-like injuries on the backs of baboons - injuries made while the animals were under anesthesia - the grafts adhered and developed a vascular system within 4 days of implantation. Signs of rejection began to appear on day 10, and rejection was complete by day 12 - a time frame similar to what is seen with deceased-donor grafts and identical to that observed when the team used skin grafts from other baboons.

As with the use of second deceased-donor grafts to treat burned patients, a second pig-to-baboon graft was rapidly rejected. But if a pig-to-baboon graft was followed by a graft using baboon skin, the second graft adhered to the wound and remained in place for around 12 days before rejection. The researchers also showed that acceptance of a second graft was similar no matter whether a pig xenograft or a baboon skin graft was used first.

Clearly there is a way to go yet, but even just a better source of useful temporary grafts for burn victims is an improvement on the current situation, and the researchers are talking about organizing clinical trials based on this work.



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