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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 '19 at 11:34
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Feel I've enough sources & data to venture an answer on this one myself now

Step one : Can we produce the pig in the first place.

Induction of donor-specific tolerance to cardiac xenografts in utero: 1998 Sep

CONCLUSION:

"xenotransplantation may be possible by induction of donor-specific tolerance in utero"

IMMUNO-INTERVENTION FOR THE INDUCTION OF TRANSPLANTATION TOLERANCE THROUGH MIXED CHIMERISM: 2011 Aug 11

  1. Clinical Studies:

"observations indicating that human organ allografts transplanted in conjunction with donor bone marrow (DBM) can survive without administration of chronic immunosuppressive therapy were made in patients who had undergone successful bone marrow transplantation (BMT) for treatment of hematologic malignancies and subsequently developed end-stage renal disease (ESRD). Kidney transplantation from the original BM donor was accomplished in these long-term chimeric recipients without requiring immunosuppressive therapy"

  1. Conclusions and Future Plans:

"there is considerable evidence that this modality can provide an effective means of inducing tolerance // in humans"

In utero hematopoietic cell transplantation: induction of donor specific immune tolerance and postnatal transplants: 2014 Nov 12

CONCLUSION:

"tolerance induction by IUHCT to allow for postnatal organ transplants without immunosuppression may hold promise"

.

First human-pig 'chimera' created in milestone study 26 Jan 2017

Interspecies Chimerism with Mammalian Pluripotent Stem Cells 2018 Jan 26

Interspecies Chimeras and the Generation of Humanized Organs 3 Jan 2019

Step two : Transferal of the donor & patient tolerant immune system from the pig to the person.

Bone marrow transplants involving the complete removal of the original bone marrow is a long established procedure.

Stem cell and bone marrow transplants

Conclusion :

In progress, may take a few days, never kept a tidy PC or bookmarks for every article read.

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No, this will likely never work - but chimeric trans plantations of 'humanised' organs might become possible.

Firstly, the process of injecting human/patient cells into an embryo would - if it works - create a chimera. Experiments of creating pig-human chimeras have (to my surprise) actually been performed, however the amount of humans cells that didn't immediately kill the embryos was very low (~0.001%), so even if they embryos would be able to reach adulthood (which the researchers didn't test) the organs wouldn't be human-like enough to allow transplantation. (source1, source2)

If the chimeric embryo's indeed survive then it might be possible to create animals that have a completely 'human' bone marrow that can be transplanted, by removing part of the pig genome that allows for the generation of bone marrow so that the injected human cells take over that role (this technique has been used successfully in rats & mice for other organs). If organs other than the bone marrow could be 'humanised' this way in pig chimeras is probably unclear since the difference between pig and human is much larger than mice and rat and might cause immune rejection issues.

Transplanting actual chimeric organs will likely never be done, since some of the cells will always be of the 'wrong' species, which would cause a lot of immune issues in some way. Since chimeras unlike hybrids will never have individual cells that combine two species, it will also not be possible to make a thymus that 'trains' the whole immune system against two species - individual T-cells might only see one type of species during maturation and therefore cause immune reactions later on.

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  • $\begingroup$ "ethics" please read the question again. $\endgroup$ – Pelinore Feb 24 '19 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 '19 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 '19 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 '19 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 '19 at 10:29

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