The idea of overcoming the limited availability of transplantation organs by using non-human donors is not a new one. Understandably however, the challenges involved as well as the potential life-saving impact are notable.

Challenges of cross-species transplantation

Already in the 1960s, it was noted that the non-human to human organ transplantation posed immunological challenges far more complex than those seen between individuals of the same species. Some of these biological challenges, along with practical limitations of non-human primates being labor and resource intensive to work with, have since been overcome by shifting focus to porcine. Distinct genetic alterations can make a pig strain with more human immune-response-compatible immunological features. Such features, along with the challenges of antibody-antigen interactions, blood coagulation dysregulation, and inflammatory responses, can be further controlled by transplantation recipient therapies that limit such unfavorable responses.

Even though full immune compatibility is still far from being fine-tuned, transplantation models suggest that such genetically modified pigs could provide organs that, combined with appropriate therapies, could survive for longer. Consequently, these results have encouraged pig to human transplantations, of which an example is a clinical trial for combatting fungus caused corneal blindness with pig corneal transplants. Organ transplantations across species however, remain to be studied through transplantation models.

What gene-editing technologies can offer?

Although both the donor and recipient play a central role in the success of transplants, our ability to modify the cross-species donor before transplantation may help to reduce the immune compatibility differences. Genetic tools develop at an increasing rate for various applications, but of particular relevance are newer gene-editing tools such as CRISPR/Cas9 which may contribute to overcoming the above listed challenges. These technologies enable precise and timely gene editing simultaneously, at multiple locations, enabling the efficient search for the right combination of donor features required.

While a pig is unlikely to save a human life today, the progress in the field of cross-species transplantations and other alternative promising methods such as regenerative medicine and tissue engineering will be increasingly interesting to follow as enabling research tools and methods develop and enable further advances to be made.

References:

Cooper, DK. & Bottino, R. 2015. Recent advances in understanding xenotransplantation: implications for the clinic.Expert Rev Clin Immunol, 11:1379-90.

Reardon, S. 2015. New life for pig-to-human transplants. Nature, 527:152-154.

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