Closer to organ transplants from pigs to humans

Transplantology experiences enormous gap between the need for organs and the availability of organs. Only in the US, waiting list for transplantations is at least five times greater than the number of donors. This gap may be bridged by other species – after decades of research, scientists are closing in on transplants from genetically modified pigs to humans.

Research in our closest cousins, grouped under “non-human primates” umbrella, shows substantial achievements. Heart transplants from pigs to baboons were functional for several years, kidney transplants endured for more than 400 days, and liver transplant recepient survived 28 days. On the basis of these results, there were suggestions to move into human trials. However, it is important to note significant barriers in this approach. Size of porcine organs is not always compatible and can enforce administration of blood-lowering drugs because of the heart being literally too big. Moreover, differences between tissues have to be met with heavy immunosuppression therapy.

Genetic modifications heavily assist xenotransplantology. Among them, there are:

  • insertions of inhibition genes: hDAF, hCD39, hCD46, hCD59, human thrombomodulin
  • anti-inflammatory genes: HO-1, A20
  • immunosuppressive molecules: Anti-CD2, CTLA4lg, hCD47, PERV siRNA, MHC
  • knock outs of porcine genes/elements: PERVs, alfa-1,3-galactosyltransferase, CMAH, B4GalNT2, vWF

The authors, M. Sykes and D. Sachs from Columbia University in New York, predict permanent organ survival in 2020s, thanks to innovations in tolerance. They remark that genetic engineering will “make [porcine] organs more compatible with human immune systems and physiology” and argue that:

Although there are other competing technologies also under development, xenotransplantation is likely to be the best near-term solution for this organ shortage.

Publication: Sykes, M., & Sachs, D. H. (2019). Transplanting organs from pigs to humans. Science Immunology, 4(41), eaau6298. doi:10.1126/sciimmunol.aau6298

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