3
$\begingroup$

Recent attempts to find reliable organ donors was using genetically-engineered (GE) pigs as heart donors. The pig's DNA is altered so that its tissues will appear identical to the patient's tissue and will not be attacked by the patient's immune system and rejected. A pig's heart is anatomically close enough to a human heart to fit to the task. All it takes is to make a GE and raise it until it is of the right age.

The issue is as follows: a human's life expectancy is much higher than that of a pig. If the patient is young enough, and the transplant succeeds, then the human will live far longer than the average pig. Will the heart hold-up throughout the lifetime of the human, or will the human need a new heart in say a decade or two?

EDIT: I have realized that actual attempts were so far limited to valves, and not entire hearts or other organs. Looking for an analogy in a human-to-human transplant, or animal-to-animal experiment, what would happen if the organ receiver is much younger than the donor itself? will the transplanted organ live the lifespan of the donor (its "original" lifespan), or will the transplant extend the life of the organ to that of the receiver?

$\endgroup$
7
  • $\begingroup$ We can't really answer such speculative questions here, please see the help. It's also encouraged to cite any supporting information when asking questions, though I don't think that will change the issue I pointed out. $\endgroup$
    – Bryan Krause
    Commented Aug 11, 2018 at 23:39
  • $\begingroup$ time.com/5159889/… I have provided the supporting information in the link. I hoped the researchers did refer to that issue but find no reference to it. That was an attempt to understand whether all organs in the body age at the same rate or is aging related to some key factors which do not affect all organs equally. $\endgroup$ Commented Aug 12, 2018 at 10:29
  • $\begingroup$ @BryanKrause I have edited my question so that it relies on actually observed cases. $\endgroup$ Commented Aug 13, 2018 at 5:55
  • $\begingroup$ @BryanKrause there is a good deal of work on this subject. An answer can be made based on real data. $\endgroup$
    – De Novo
    Commented Aug 13, 2018 at 6:33
  • $\begingroup$ @DeNovo I think your answer is fine and will be helpful for the OP, but it doesn't directly answer the question asked which was about the life expectancy of a pig vs. human and how that impacts the lifespan of a xenotransplant, and about hearts, not valves. Allotransplants and mechanical valves also have limited lifespans. $\endgroup$
    – Bryan Krause
    Commented Aug 13, 2018 at 14:21

1 Answer 1

2
$\begingroup$

tl;dr

Graft survival, even with allotransplantation (human donor to a human host), is not equal to an average human lifespan. It's much shorter (11-16 years on average). Porcine grafts (which often last over 15 years) do not seem to be limited by the average pig lifespan (which, google tells me is 6-10 years). In both allo and xenotransplantation, graft failure and host survival are issues of the immune response to the graft, not of the expected lifespan of the donor.

Full answer:

Will the heart hold-up throughout the lifetime of the human, or will the human need a new heart in say a decade or two?

Lets answer this, first, for a heart transplanted from a human donor, an allograft. Even from a human donor, the heart is unlikely to hold up for a normal human lifetime. Heart transplant survival has improved greatly over the last five decades, but median survival in an adult is now 11 years. In pediatric patients, it's 16 years. The main problems are cardiac graft vasculopathy, malignancy, infection, and immune rejection. Transplant is a treatment, not a cure, and a major challenge of transplant as therapy is managing the immune response. Rejection and graft vasculopathy are (generally) related to immune injury of the transplanted organ. Malignancy and infection are related to immune suppression of the host.

Xenotransplant (transplantation from a non-human donor) adds an additional complication to the challenge of managing the immune response. Here, the range of non-self antigens is even greater, and the graft will be attacked by complement and other aspects of the innate immune system, as well as the adaptive immune system. This leads to graft destruction, often in the first hour after transplant. There have been advancements using transgenic pigs that solve some of these problems, with improvement in survival in pig to primate trials. Personally, I'm skeptical that CRISPR techniques will easily solve all of the problems of transplant immunology, but transgenic animals have moved things forward substantially over the last 15 or so years (see this review)

As far as porcine valves are concerned, they are treated to reduce their antigenicity (a protocol that hasn't worked for cardiac xenotransplants). Paradoxically, graft survival in older patients is quite good, with most valves lasting beyond 15 years. This may have something to do with age related decrease in immune function, but regardless, porcine tissue (at least from a valve), seems to hold up quite well.

There is good access to data on cardiac allotransplant survival (both adult and pediatric) directly from the international society for heart and lung transplant. There is a good review of pediatric transplants here. You can read more about cardiac graft vasculopathy here

As far as xenotransplantation is concerned, there was an excellent issue of the international journal of surgery, november 2015, that has a number of articles reviewing xenotransplant. Many are available without a paywall, and it's a good place to read up on this. This article from that issue discusses immunological challenges in xenotransplantation from pig to primate. You can read more about this here, but it's beyond a paywall. A good discussion of the overall history of xenotransplantation was reprinted in that issue, here

$\endgroup$

You must log in to answer this question.

Not the answer you're looking for? Browse other questions tagged .