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mayonnace t1_ivpoir5 wrote

Reply to comment by derioderio in Does the dna of transplanted organs (organic material) change after the recipient successfully recovers? by theZoid42

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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