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Comment by duckerude | Hacker News Reader

> Investigators used a cocktail of sugar and detergent to get rid of all the cells and blood vessels from a lung taken from a donor pig. This left behind a support scaffold made from proteins - the lung's "skeleton" if you like.

If I'm reading this correctly, a donor is still needed, and the main advance is that the lung is less likely to be rejected because the cells match the recipient.

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The difference here is before the donor had to be a near perfect fit. With this method they can build the scaffolding from any dead body then use recipients cells for the tissue.

So we go from a couple thousand lung transplants a year with 50% mortality to potentially unlimited and much lower mortality (don't really know the mortality rate here but so far looks promising and better than).

Along with that, the fact that the scaffolding isn't living cells means that they can likely preserve the lungs for longer periods of time for future recipients too. That should be a massive boon for transplants since they'll no longer need to be a "Get here in 30 minutes or the organ won't be viable long enough" kind of situation.

Additionally the donor doesn't necessarily have to be human.

If pig lungs are a good enough a fit.

Pig lungs are extemely close to human lungs --- that's why a lot of such research is done on them.

Looks like the age of chimeras is upon us.

It's already here to an extent. Pig heart valves have already been transplanted into humans.

Would pig lungs offer an advantage somehow in terms of performance?

I was thinking in terms of availability.

There are more pigs in Australia than people, comprised of about 24 million feral pigs and about 4.5 million pigs produced each year for consumption.

Australia's population is currently about 25 million.

The number of normal pigs available isn't really significant... Even if you assume that the donor pigs wouldn't be heavily genetically engineered (and they probably would be), the risk of xenogeneic infection (ie pig viruses being carried over to the patient) means that they'd have to be raised under sterile conditions, so normal pigs are useless. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88959/ https://www.ncbi.nlm.nih.gov/pubmed/11041495

Thanks for the reply.

Fair points.

We’re not talking about xenotransplantation of living tissues though.

Still, there would probably be a non-zero chance of xenoinfection from non-human non-cellular scaffold use in bioengineered organs.

You’re probably right that if this were to become a use case for non-human parts the source probably wouldn’t be regular far animals.

We’re not talking about xenotransplantation of living tissues though. I appreciate that. I did have the idea that the stringency of the washes in decellularization wouldn't be enough to get rid of viruses. Looked into it and it turns out that might not be true. Washing might be enough: https://www.ncbi.nlm.nih.gov/pubmed/12115437

Not sure how compatible this is w/ the protocol used in the OP.

That didn't even occur to me. If they were compatible for this in humans, then a huge amount of the meat industry could benefit by providing the lungs that they can't always easily sell (organ meat isn't as popular for humans at least).

it's also a boon towards eventually 3d printing the scaffolding instead of using a pregrown one

I’m not sure how well this works with lungs, but for less vital tissues (ligaments, cartilage for instance) it allows animal tissues to be used in humans. Instead of needing a human organ, you could potentially remove the cells from a pig organ and then be repopulated by human cells.

It might (completely guessing here) also mean that lungs that wouldn't be suitable for normal transplant due to health or condition, might be suitable to be used in this way.

I wonder how much this process reverses the age of the lungs, if you take the lungs of an 80 year old, wash them, reseed them and put them in a 20 year old, what’s the result?

I don't work in this area, but ECM scaffolds undergo significant change with age. Crosslinks and age-related remodelling degrade the mechanical properties of the scaffold and interfere with normal cell migration and differentiation.

You would want to start with a healthy organ before decellularising and reseeding.

But perhaps not quite as critical as for current transplants? At least that's my uneducated guess... anyone know?

If that would work I guess people would like to "refresh" their organs anyway from time to time to avoid failure.

Yes, though I would expect the risk of complications from this procedure will outweigh the benefit for healthy patients for many years after it becomes a "routine" operation for those with lung disease.

Weird thought what if a 20'something put cells in a bank and had organs generated from them later in life.

I imagine that this just happens an easy way to get a "scaffold" to build the lung on for the moment being.

I think, the scaffold is an extremely important part of the process, it has chemical and physical signals which allow stem cells to develop properly. I haven’t heard of a plastic scaffold being used except in Macchiarini scandal, where the patients either died or had to have their artificial windpipe replaced. And that was for a windpipe which is a layered 2D structure, not something like a lung with an enormously complicated 3D vasculature. I suspect artificial scaffolds will be far more difficult than the process covered here.

Your comment prompted me to find out about the Macchiarini scandal, which I had not previously been aware of. That's some seriously scary shit that went down there! When your experimental technique fails - again and again - and multiple people die - one after another - and you still go on doing it... that's just sick. Or dedication, I presume.

The section about the bronchoscopy is this article is terrifying:

https://www.bbc.com/news/magazine-37311038

Stem cell science must above all avoid another Jesse Gelsinger case. Superstar researchers will always want to take chances, but the risks have to be strictly managed by the community or else there will be a backlash and progress will be set back by decades.

Macchiarini seems to have told lies about everything, not just his research. Strikingly, he told one journalist that he would marry her and the Pope himself would officiate (https://www.vanityfair.com/news/2016/01/celebrity-surgeon-nb...), while he in fact did not know the pope and also was already married.

This is still ultimately a limitation not an impossibility. I can easily imagine some form of tissue deposition like 3D printing where you use laser activated gene regulation to control cell fate of the stem cells digitally at high spatial resolution.

From what I understand, artificial ECMs can be more difficult to build in some ways, but if you can figure out how to incorporate the right signaling factors into an artificial collagen matrix, you can avoid a lot of challenging biocompatibility/immune reaponse problems. Also, I believe most cells are differentiated before being seeded onto the scaffold.

Thanks for the information. I didn’t realize there were still biocompatibility issues even after the detergent process.

This can be done autologously, if mechanical or biological redundancy is available: heart, kidney, liver, etc. lungs are hard, but the talk from old colleagues at UTMB are near-primate & primate donors. There are significant ethical issues with the latter.

lung transplantees only live for around a year post-transplant. rejection is much more common with lungs than other organs

This is anecdotal only, but I know several CF patients who have lived for years on transplanted lungs.

This journal article suggests a median survival rate of 5.8 years:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594127/

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