The Prospects for Pig to Human Xenotransplantation

The use of pigs to expand the supply of donor organs for human patients is coming closer to reality. A number of new technologies are enabling researchers to remove the various blocking issues in cross-species transplantation: cheap and efficient gene therapy, decellularization, and so forth. It is still proving to be challenging. Ultimately this will be, I suspect, a comparatively brief transitional technology, eclipsed in the decades ahead by the ability to grow organs from a patient's own cells. Here is an update on the state of the xenotransplantation field:

A US lab has performed about 50 pig-to-primate transplants to test different combinations of genetic modifications in the pig and immune-suppressing drugs in the primate. Even so, the team has not had a primate survive for longer than a few days. The complexities of the immune system and the possibility of infection by pig viruses are formidable and drove large companies out of the field in the early 2000s. That trend may now be reversing, thanks to improved immunosuppressant drugs and advances in genome-editing technologies such as CRISPR/Cas9. These techniques allow scientists to edit pig genes, which could cause rejection or infection, much more quickly and accurately than has been possible in the past.

Some researchers now expect to see human trials with solid organs such as kidneys from genetically modified pigs within the next few years. United Therapeutics has spent $100 million in the past year to speed up the process of making transgenic pigs for lung transplants - the first major industry investment in more than a decade. It says that it wants pig lungs in clinical trials by 2020. But others think that the timeline is unrealistic, not least because regulators are uneasy about safety and the risk of pig organs transmitting diseases to immunosuppressed humans. "I think we're getting closer, in terms of science. But I'm not yet convinced we've surpassed all the critical issues that are ahead of us. Xenotransplantation has had a long enduring reality that every time we knock down a barrier, there's another one just a few steps on."

Over a decade of little progress towards whole organ transplants, a few research teams and start-up companies began pursuing pig tissue transplants: a much simpler goal than using solid organs because the immune response is not as severe. In April, Chinese regulators approved the use of pig corneas from which all the cells have been removed. Also on the near horizon are pig insulin-producing islet cells that might be transplanted into people with diabetes. The first commercially available islets are likely to come from technology designed by Living Cell Technologies, that has developed a process to encapsulate pig islet cells in a gelatinous 'dewdrop' that protects them from the human immune system. The product is currently in late-stage clinical trials in several countries. Patients implanted with the cells have survived more than nine years without evidence of immune rejection or infection. "I think people are coming around to look at xenotransplantation in a more-favourable light knowing that we have strong safety data."

Solid organs still pose a challenge. The handful of researchers who have continued to work with them have solved some of the problems, such as identifying other key pig antigens and the correct combinations of immunosuppressant drugs. But different organs have different problems: kidneys may be safer than hearts, for instance. Lungs are extremely difficult to transplant, because they have extensive networks of blood vessels, which provides more opportunities for primate blood to meet pig proteins and to coagulate.



I still think growing a patient matched organ from iPSC cells inside a pig and then transplanting that back into the patient is a more viable approach.

Posted by: Jim at November 11th, 2015 8:17 PM
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