Cristina Costa: 'Immune rejection is the main barrier to take xenotransplantation to the clinical practice''

The European Cells and Materials journal has just published a review article of your research group on xenotransplantation. What does this procedure work?

Xenotransplantation is the transplantation to humans of cells, tissues and organs from animals, mainly pigs, although there are also cases where bovine tissues are used.

The idea behind the review was to elaborate a history of all the research on xenotransplantation my group has carried out, with emphasis on their use in repairing cartilage.

Could we say that xenotransplantation is a standard procedure in clinical practice?

Yes, it is a more established clinical procedure than one would believe. For example, most transplanted heart valves nowadays are of animal origin.

However, I have carried out research in this area for a long time and during these years I have seen many changes; in the early nineties, it seemed that xenotransplantation would solve it all, but over the years the results were not as expected, and the arrival of stem cells changed the landscape.

What is the current situation, then?

At the moment, new available genomic editing techniques, and increased investment, mainly in the United States, have bumped xenotransplantation to a privileged position. There has been a significant change.

However, the only current way of achieving solid organ transplantation is by allogeneic transplantations (using cells from another person). We are not yet able to generate non-human organs for xenotransplantation, but there is the potential for that.

And what would be the application of xenotransplantation in cartilage repair?

Cartilage is a tissue of very limited self-regeneration. Cartilage transplantation between humans is not widely applied, but they have already been successful cases regarding the regeneration of this tissue in traumatic injuries - cases of athletes undergoing this procedure are known. There are autologous transplantations, performed with cells from the same person, or allografts, with cells from another person.
An autologous transplantation of chondrocytes is an effective treatment but it can only be done in a limited number of cases depending on the quantity and quality of the cells. If we get xenotransplantation of porcine chondrocytes to work, we would be able to select those cells that have a greater capacity for regeneration and cells and transplanted tissues could be adapted by genetic engineering to the desired clinical applications. This technique involves an almost unlimited source of cells that can be obtained under very high quality standards.

What remains to be done?

In the future, we could also perhaps apply this kind of xenotransplantation in patients with early osteoarthritis or rheumatoid arthritis. They are very prevalent diseases that we are currently trying to prevent because they cannot be stopped; therefore, if we were to apply to xenotransplantation in this area the social and economic impact would be huge.

Unfortunately, we have not yet been able to find a way to avoid rejection. In fact, we could say that immune rejection is the main barrier we are facing to take the final leap to the clinic. In that sense, our work exposes the current state of the art and the unmet needs. We are still at the basic research stage; so far, we have identified some molecular mechanisms associated with rejection in humans of tissue or cells from other animals, and some of the genetic modifications that might solve them.

Links:

Xenotransplantation of pig chondrocytes: therapeutic potential and barriers for cartilage repair. R Sommaggio, M Uribe-Herranz, M Marquina, C Costa