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So the immune system doesn't calibrate (for want of a better euphemism) to recognize it's own cells until fairly well along in fetal development & the major components of the immune system (antibodies, white blood cells, etc) are all produced by the bone marrow.

Those are the known details that cause me to wonder if this (below) might not be a viable approach.

Introduce the patients cells to a pig fetus before it's immune system has been set & it will be born with an immune system that recognizes both it's own cells & the patients cells as it's own.

Kill the patients own marrow (as per a normal bone marrow transplant) & transplant the pigs bone marrow into him giving him an immune system that recognizes both his cells & the pigs as it's own.

If my understanding is correct you should then be able to transplant any other organs from the pig into the patient without any tissue rejection issues.

I am only interested in the science so (any legal & moral issues aside) are there any major factors I'm unaware of to suggest this approach is a non-starter?

See Xeno: The Promise of Transplanting Animal Organs into Humans By David K. C. Cooper M.D., Robert P. Lanza M.D. Published 23 March 2000 by Oxford University Press, specifically the section on "The Induction of Chimerism Before Birth" from page 117 onward in this link.

That talks about my suggested first step (though in reverse), creating a human with immunity to cell rejection of a donor animals cells, which isn't much use to anyone who's already been born.

So I flipped the idea.

A Thymus transplant might be needed as well.

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  • $\begingroup$ Comments are not for extended discussion; this conversation has been moved to chat. $\endgroup$ – AliceD Feb 24 at 11:34
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No, this will not work.

Like you mentioned, when the immune system develops it first has to learn which antigens are 'self' and should not be recognised. This process is called 'negative selection' and especially important for T-cells, for which it happens in the thymus (after which they are also named). Special cells in the thymus express almost all the genes of the organism so the cells who recognise them can get sorted out.
From this follows that you specifically need a thymus in the pig that expresses both all human AND all pig genes (otherwise the pig will die).

If you just inject some cells of a patient into pig fetus, this will in most cases either outright kill fetus or do nothing (if the fetus can get rid of the injected cells) or lead to a couple of random unspecified (and differentiated) cells somewhere in the adult pig. None of this gets you any closer to your goal.

In order to actually generate a pig with a hybrid/chimera thymus you'd either have to engineer the genome of the pig so that it has all human genes but only expresses them in the thymus (which is nowhere near remotely possible for at least ~20 years) or inject human embryonic stem cells into the pig fetus and pray that the weird chimera you're creating survives long enough to actually develope an immune system (spoiler: even if it does, a VERY angry ethic committee is going to get you into jail).

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Some of the information contained in this post requires additional references. Please edit to add citations to reliable sources that support the assertions made here. Unsourced material may be disputed or deleted.

  • $\begingroup$ "ethics" please read the question again. $\endgroup$ – Pelinore Feb 24 at 11:35
  • $\begingroup$ @Pelinore: I read the question, and my answer is a clear NO irregardless of the ethics aspect $\endgroup$ – Nicolai Feb 24 at 11:37
  • $\begingroup$ "otherwise the pig will die" can you explain why pigs with humanized organs don't die then, we've almost two decades of experimentation doing just that and I don't recall ever reading anything about a problem with pig mortality arising from that? $\endgroup$ – Pelinore Feb 24 at 11:38
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    $\begingroup$ @Nicolai your post could be improved with more thorough references. Right now you've just linked to the wikipedia page on T-cells, but you make very specific statements about what would or couldn't happen in various experiments. $\endgroup$ – De Novo Feb 25 at 20:12
  • $\begingroup$ @DeNovo I'll try to see if I can find some references but it wont be easy since these are mostly hypothetical experiments that noone would actually do (and therefore write about), like injecting adult cells into an embryo. $\endgroup$ – Nicolai Feb 26 at 10:29

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