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derioderio t1_ivorruk wrote

Generally no. The recipient has to take immunosuppressants for the rest of their life so that their immune system doesn’t attack the ‘foreign’ cells in the transplanted organ.

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Training_Ad_2086 t1_ivppm5f wrote

Does the transplanted organ keeps deteriorating even with immunosuppression? Or are immunosuppressive medication 100% effective?

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phriendlyphellow t1_ivpwr4n wrote

The immunosuppressants simply limit the host’s immune system from attacking the foreign/donor cells/tissues/organs. In fact, the host’s body will, under immunosuppression, do everything it can to keep the vital organ alive. This is why people can continue to live longer and healthily after transplants.

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bettinafairchild t1_ivqib3e wrote

Little by little, yes, they deteriorate. Some transplants, like heart, last an average of 10 years, while kidneys last an average of 20 years.

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mayonnace t1_ivpoir5 wrote

You said, "Generally". How can they change anyway? I've never heard of horizontal gene transfer or such between host and transplanted tissue. At most, expression levels might change, I guess. Hmm... Actually, could the tissue be genetically modified via gene therapy before the operation? I mean, theoretically, like if the tissue could stay alive for that much time and also not lose their cells' specifications. It might be interesting.

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derioderio t1_ivpub5k wrote

I said generally because I'm not enough of an expert to know if there are exceptions, not because I know that there are exceptions.

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phriendlyphellow t1_ivpyn4r wrote

And to your point about gene therapy…

This is a hot area of synthetic regenerative biology. Instead of dealing with donor matching and immunosuppression, what if you could extract a patient’s cells, reprogram them to a pluri- or multi- potent state, use gene editing tools like CRISPR to correct any degenerative genetic defect, grow the patients pool of cells, infuse them into a decellularized extracellular matrix (ECM) of an organ they need, and cisplant (as opposed to transplant, because it’s their own cells).

Theoretically possible and a number of these techniques have made it past the proof of concept stage.

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ArtyWhy8 t1_ivr0e0y wrote

Just was hearing about something like this being done. Funny enough it all comes back to the Thymus. Here’s the Radiolab episode I heard about it on.

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phriendlyphellow t1_ivpxpw9 wrote

We don’t fully understand the mechanism of horizontal gene transfer (HT). If there is HT between host and donor, it would like be transposable elements. And we don’t really understand how genetic information not only escapes the nucleus and cellular membrane of one cell, then transports through the extracullular matrix (ECM) (or vasculature?) to another cell, penetrates the cell membrane, and then navigates to the nucleus, and embeds itself in the other-origin cell… all without being degraded by nucleases that are designed to prevent free-floating nucleic acids (RNA and DNA). 🤷

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Elocai t1_ivqhc3k wrote

Expressions will change as the host has certanly a diffrent metabolism and hormon levels, in addition to possible epigenitic changes.

I think: that genetic treatment of a organ is currenlty not possible. Your goal would be to remove all immuno activating markers and replace them with the host ones. But for that to happen the old markers have to be removed which commonly happens when the cell dies. A duplication of a treated cell wouldn't solve the issue either at first iteration as the old markers would still be present, just their concentratio n per cell would be lower. With following iterations and natural removal of the old markers there would probably be a state achieved that would be ideal for tranplant. But dead and duplication can have big inteervals, like sure if you would take gut it would take just a couple days to get there but with a kidney or liver it would take years if not decades. Keeping a organ alive for that long would be a big achievemen.

You might then thing, yeah lets just do it in the donor, but then you get the same issues with a immune reaction, but now just on the donors side.

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mule_roany_mare t1_ivqn70i wrote

I think there has been some experimentation with stripping an organ down to a collagen frame & loading it up with a recipients stem cells.

I think the closest we would ever get to native organs is identifying what alerts the recipient immune system & CRISPRing those bits of the new organ with the recipient's DNA. This would work just as well with animal organs with the advantage of using CRISPR while it's still in the animal.

It's probably not the best idea to perfectly recreate the organ that failed in that environment anyway.

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phriendlyphellow t1_ivpw5d6 wrote

“How can they change anyway?”

All DNA in every cell is subject to “random” mutations over time as cells replicate. DNA damage from radiation and/or oxidative stress causes the changes. Very rarely, there is an accepted mismatch in replication.

To your other point. Horizontal gene transfer is not a whole genome switch, but a rare event of a transposable element arising in a different species. Horizontal transfer of transposable elements is poorly understood and the underlying mechanisms are still largely unknown. You can read more in this 2020 paper. https://www.nature.com/articles/s41467-020-15149-4?error=cookies_not_supported&code=5df6700e-6c24-40ba-9192-85e2acb0d513

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AnnexBlaster t1_ivs1tmr wrote

No the DNA does not change. The DNA cannot change unless there is genetic engineering happening like CRISPR. (Or random mutations)

There are things called retrotransposons (LINEs) that are able to move DNA but these are rarely expressed and as far as I know they are only intercellular and don’t move between cells.

But think about it, in an organ there’s hundreds of thousands to millions of cells each with their genome. The genome can not change on this scale, it is evolutionarily disadvantageous for a genome to be able to change that much (could lead to cancers and overall disfigurement of the proper transcription profile that the specific cell needs to function).

As others have said, organ transplant recipients need to take immunosuppressive drugs because the immune system recognizes the organ is not self. Doctors try to match the HLA profiles (the main receptors immune cells use to recognize self) so that as little rejection happens as possible, but it’s still not enough in many cases.

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rachaeltalcott t1_ivsu7rp wrote

Solid organs contain macrophages, specialized to each organ. When a solid organ is first transplanted, the macrophages have the same DNA as the donor, but over time they can be replaced from the bone marrow of the recipient. It's not as simple as a constant stream of macrophages coming from the bone marrow, though. The "resident macrophages" can be produced from within the organ, from their own population of stem cells. But if something happens and the population of these cells within the organ is depleted, new cells can come in from the bone marrow of the recipient and therefore would have the DNA of the recipient.

This process of movement of macrophages can also go the other way. Some people who have received a transplanted organ end up with donor macrophages in places like skin and lymph nodes.

The number of cells that are moving around like this is fairly small. The large majority of the cells of the organ aren't replaced from outside of the organ and therefore keep the original DNA of the donor.

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Drasticshift t1_ivqaea1 wrote

as someone who doesn't know anything about the exact science behind it... I am aware of recipients requiring to take immuno suppressants to prevent organ rejection. But there has been a rare moment where the recipients blood type changed after receiving a new organ transplant. scienctific research is on the edge of a few breakthroughs that would make it possible to change blood type of organs so the patient never has to take immuno suppressing drugs. https://www.newscientist.com/article/2308568-lung-with-switched-blood-type-is-step-towards-universal-donor-organs/

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michalv2000 t1_ivsk71d wrote

I guess the main reason you're asking about this is the anti-rejection medication. The DNA doesn't change after transplantation, BUT there is one way to get rid of anti-rejection pills. The bone marrow transplantation. It has to be from the same person that donated their organ as well.

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theZoid42 OP t1_ivthe8c wrote

That’s interesting. Why is that the case?

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michalv2000 t1_ivukip6 wrote

It's because the bone marrow is responsible for your immune system. When you take the bone marrow from someone's body and put it into somebody else, the transplanted organ would basically "think" that it's still located in its' original body.

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googlecansuckithard t1_ivrvbq7 wrote

Every cell obtains its DNA from either a single parent cell or two parent cells depending upon method of reproduction. Because organs are specialized cell types, it follows that an organ once removed maintains the DNA of the host the organ came from direct virtue- e.g. organ cells are of a specialized type hence only heart cells can reproduce to create heart cells, etc. he plausible exception: the stem cell, but this would take a rather long time and would require that the organ have reproduced every cell composing it at least once, and that assumes that stem cells are plentiful enough as to fashion the kind of counts needed, which apart from neonates, they are not as the rule.

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