Transplanted pig hearts have been kept alive in baboons for longer than ever before, according to research in Nature Communications, with one heart lasting 945 days. The hearts were connected to the circulatory system of the baboons but did not replace the animals’ own organs, and were prevented from being rejected by a combination of genetic modifications and drugs. The authors say their results bring the prospect of human trials of pig heart transplants closer.
Dr. Kenneth Bondioli, Professor of Animal Sciences, Louisiana State University (webpage):
Expertise: Production of transgenic animal models for biomedical and agricultural applications.
“I think this paper represents progress towards clinical application of xenotransplantation. Survival times reported here are approaching clinical relevance especially for ‘bridge transplants’ until a human organ becomes available. I think the combination of genetic modification and immunosuppressive regimen reported here is particularly important. Clinical success of xenotransplantation will rely upon a combination of genetic modification and immunosuppressive regimen and both must be developed. It is likely that the best combinations will occur when the immunosuppressive regimen is tailored for the specific genetic modification rather than blanket suppression of the immune response.”
Dr. Max Rothschild, Distinguished Professor in Agriculture and Life Sciences, Iowa State University (webpage):
Expertise: Animal breeding and genetics, pig genetics.
“Too few organs exist from humans to provide all the transplants required in the US and other places in the world. In addition, to be transplanted human organs must have the same or nearly the same ’tissue type’, combined with medications that prevent rejection of the transplanted organs. So generally speaking, under the best situations both the right genetics and anti-rejection medicines are needed.
“One long term way to supplement human to human organ transplants would be to use organs of similar size from a domestic species. This could only happen if they were genetically engineered so they expressed human antigens. Research using pig organs, hearts in particular, have been ongoing for some time. They are tested in primate (baboon) models. In the past all animals in these types of experiments have died from delayed graft rejection in periods of 179-236 days. The combination of genetically engineered hearts and new drug therapy discussed in this research has allowed the median survival to be 298 days and in one case 945 days; a considerable improvement.
“Does this bring us any closer to human trials? The simple answer is yes but the finish line is still quite far away. However, progress like this allows for other strategies and combinations to be examined and may eventually point the way to eventual trials in humans.”
Dr. Willard Eyestone, Research Associate Professor, Reproductive Biology / Biotechnology, Virginia Tech (webpage):
Expertise: Developmental biology and genetic modification of animals.
“This paper presents some very encouraging data on the development of xenotransplantation for organ replacement. Here, genetically-modified pig hearts were transplanted into baboons, where they functioned for nearly 3 years in one case, much longer than previously reported. Success was attributed to genetic knockout in pig hearts of alpha 1-3 galactosyltransferase and knock in of of two thrombomodulatory proteins, plus an aggressive immunosuppressive regime in the baboons. The good news emanating from these findings is that the system used to achieve these results, perhaps with some modifications, should be applicable to early-stage human trials using pig hearts with similar genetic modifications. Refinement of these promising results should go a long way to translating xenograft technology for human medicine, and relieve the vast shortage of human hearts, kidneys and livers required to save the many patients who die every day waiting for an organ that never comes.”
Declared interests (see GENeS register of interests policy):
No interests declared.
‘Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft‘ by Mohiuddin et al, published in Nature Communications on Tuesday April 5, 2016.