10 ms·

> 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 supp

> 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.

Engineering-MD 8y ago
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.
Drakim 8y ago
I imagine that this just happens an easy way to get a "scaffold" to build the lung on for the moment being.
- Brakenshire 8y ago
  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.
  - _0ffh 8y ago
    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.
    - Brakenshire 8y ago
      The section about the bronchoscopy is this article is terrifying: https://www.bbc.com/news/magazine-37311038 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.
    - vilhelm_s 8y ago
      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-nbc-news-producer-scam https://www.vanityfair.com/news/2016/01/celebrity-surgeon-nb...), while he in fact did not know the pope and also was already married.
  - Ultimatt 8y ago
    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.
  - claytonius 8y ago
    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.
    - Brakenshire 8y ago
      Thanks for the information. I didn’t realize there were still biocompatibility issues even after the detergent process.
theBobBob 8y ago
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.
- Brakenshire 8y ago
  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?
  - biofox 8y ago
    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.
    - improbable22 8y ago
      But perhaps not quite as critical as for current transplants? At least that's my uneducated guess... anyone know?
  - thefounder 8y ago
    If that would work I guess people would like to "refresh" their organs anyway from time to time to avoid failure.
    - dmurray 8y ago
      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.
    - kls 8y ago
      Weird thought what if a 20'something put cells in a bank and had organs generated from them later in life.
point78 8y ago
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).
- simcop2387 8y ago
  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.
  - TheSpiceIsLife 8y ago
    Additionally the donor doesn't necessarily have to be human. If pig lungs are a good enough a fit.
    - userbinator 8y ago
      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.
      - rcxdude 8y ago
        It's already here to an extent. Pig heart valves have already been transplanted into humans.
    - matte_black 8y ago
      Would pig lungs offer an advantage somehow in terms of performance?
      - 8y ago
thechao 8y ago
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.
bsamuels 8y ago
lung transplantees only live for around a year post-transplant. rejection is much more common with lungs than other organs
- bdcravens 8y ago
  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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594127/

Engineering-MD 8y ago

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.

Drakim 8y ago

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

Brakenshire 8y ago
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.
- _0ffh 8y ago
  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.
  - Brakenshire 8y ago
    The section about the bronchoscopy is this article is terrifying: https://www.bbc.com/news/magazine-37311038 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.
  - vilhelm_s 8y ago
    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-nbc-news-producer-scam https://www.vanityfair.com/news/2016/01/celebrity-surgeon-nb...), while he in fact did not know the pope and also was already married.
- Ultimatt 8y ago
  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.
- claytonius 8y ago
  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.
  - Brakenshire 8y ago
    Thanks for the information. I didn’t realize there were still biocompatibility issues even after the detergent process.

theBobBob 8y ago

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.

Brakenshire 8y ago
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?
- biofox 8y ago
  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.
  - improbable22 8y ago
    But perhaps not quite as critical as for current transplants? At least that's my uneducated guess... anyone know?
- thefounder 8y ago
  If that would work I guess people would like to "refresh" their organs anyway from time to time to avoid failure.
  - dmurray 8y ago
    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.
  - kls 8y ago
    Weird thought what if a 20'something put cells in a bank and had organs generated from them later in life.

point78 8y ago

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).

simcop2387 8y ago
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.
- TheSpiceIsLife 8y ago
  Additionally the donor doesn't necessarily have to be human. If pig lungs are a good enough a fit.
  - userbinator 8y ago
    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.
    - rcxdude 8y ago
      It's already here to an extent. Pig heart valves have already been transplanted into humans.
  - matte_black 8y ago
    Would pig lungs offer an advantage somehow in terms of performance?
    - 8y ago

thechao 8y ago

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.

bsamuels 8y ago

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

bdcravens 8y ago
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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594127/