[HN Gopher] 'Mini liver' will grow in person's own lymph node in...
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       'Mini liver' will grow in person's own lymph node in bold new trial
        
       Author : Brajeshwar
       Score  : 167 points
       Date   : 2024-04-03 13:57 UTC (9 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | martibravo wrote:
       | Grey's Anatomy predicted this. [1]
       | 
       | [1] https://mirm-pitt.net/from-the-lab-of-dr-eric-lagasse-to-
       | abc...
        
         | isodev wrote:
         | Shonda Rhimes always gives us high quality content.
        
       | gamepsys wrote:
       | > The approach is unusual: researchers injected healthy liver
       | cells from a donor into a lymph node in the upper abdomen of the
       | person with liver failure. The idea is that in several months,
       | the cells will multiply and take over the lymph node to form a
       | structure that can perform the blood-filtering duties of the
       | person's failing liver.
       | 
       | The first treatment was performed on March 25th, so we have
       | several months to see how this will go. Initial recovery looks
       | good. Of course this is huge because we don't have enough livers
       | for everyone that needs one. If we can grow a new one with a
       | little help than that will greatly increase the number of people
       | with failing livers we can help.
        
         | thimkerbell wrote:
         | Well this is good news.
         | 
         | But how much of a whole liver does a recipient need, now, to
         | get good enough liver function? I thought they were famous for
         | growing back.
        
           | sp332 wrote:
           | If the liver gets full of hard scar tissue, it can physically
           | constrain the hepatocytes from making more liver tissue.
           | https://www.news-medical.net/news/20200824/Large-animals-
           | wit...
        
           | sandworm101 wrote:
           | Surprisingly little. Most of the liver stand by at idle ready
           | to filter intermittent massive doses of things, such the
           | stuff arriving in your bloodstream after a big meal. This is
           | what makes many liver diseases so evil. A person can live
           | basically free of symptoms for many years as their liver
           | struggles and is progressively damaged by some substance
           | (alcohol). Until one day the amount of remaining functional
           | liver dips slightly below the minimum needed to sustain daily
           | functions. After decades of drinking, over the course of a
           | month a functional alcoholic can go from being a happy drunk
           | to a patient dying in hospital in need of a new liver.
        
             | _a_a_a_ wrote:
             | I'm rather unclear about the speed of regrowth. From one
             | source (the web?) It was a matter of years, yet talking to
             | a herpetologist (edit: hepatologist. Blame voice
             | recognition) in a pub, she said it can regrow 80% of itself
             | in a matter of weeks. Assuming a healthy liver, how fast is
             | regrowth?
             | 
             | Assuming a cirrhosed liver , how would that affect regrowth
             | time? TIA.
        
             | raisedbyninjas wrote:
             | So alcoholics should do a periodic stress test of binge
             | eating to get an early warning.
        
               | ajuc wrote:
               | Just do blood tests for liver diseases markers every
               | year. Even if you're not an alcoholic - there's many
               | other diseases that result in similar damage.
               | 
               | For example if you have asthma and especially if you have
               | colitis ulcerosa or crohn's disease - you're at much
               | higher risk of PSC - an autoimmune liver disease which
               | does basically the same thing as decades of drinking.
        
               | boredemployee wrote:
               | Tangentially, I just found out in a routine test that I
               | have a condition called "gilbert's syndrome" [0]. It's
               | harmless tho. It came from my parents, it seems. My dad
               | died of liver cancer, but I don't know if he was
               | diagnosed with that syndrome and if they were related.
               | 
               | [0]. https://www.mayoclinic.org/diseases-
               | conditions/gilberts-synd...
        
               | adamredwoods wrote:
               | PSC is a rough disease with the bile ducts. I'm surprised
               | we haven't any treatment for it yet.
        
             | hinkley wrote:
             | One of our dogs had days to live by the time we found out
             | he had a congenital defect that caused a fibrous liver. In
             | retrospect some parts of his personality may have been
             | symptoms, but we were wrecked.
        
           | Jaepa wrote:
           | They are to an extent. Cirrhosis is permanent. Other
           | conditions such as fatty liver are reversible-ish.
           | 
           | The issue is that the liver is basically fully functional
           | until after you've destroyed ~88% of it.
           | 
           | For a tortured analogy it's a lot like a DB. Most of them
           | time you're well under your total capacity. Even short spikes
           | in queue length aren't an issue. But once you hit the tipping
           | point there are cascading failures.
        
             | skissane wrote:
             | > Cirrhosis is permanent
             | 
             | Cirrhosis has been observed to reverse in some individuals.
             | It is still permanent for most patients, and we shouldn't
             | give people with it false hope, but its reversal isn't
             | impossible. Most commonly cirrhosis reversal is observed
             | after chronic viral hepatitis is cured by antiviral
             | treatment. There are even a handful of clinical case
             | reports of alcoholic cirrhosis reversing after extended
             | abstinence from alcohol, even though that is a rather rare
             | outcome. I remember reading a case report (sorry can't find
             | it right now), of a Japanese alcoholic diagnosed with liver
             | cirrhosis, who then was severely disabled by a stroke, and
             | had to be moved to a nursing home. He never drank again
             | because he physically couldn't drink without nursing staff
             | assistance, and they weren't going to give him any alcohol.
             | Roughly 20 years later, his cirrhosis had disappeared. Of
             | course, this is a rare outcome (he likely had favourable
             | genetics, plus rarely does an alcoholic find relapse
             | physically impossible), but it shows it can happen.
             | 
             | This is why there is a lot of hope that some of the liver
             | disease drugs currently in the clinical pipeline may be
             | able to reverse cirrhosis (and if not them, maybe their
             | future successors). However, current trials are focusing on
             | fibrosis not cirrhosis. And they run into the difficulty
             | that what counts as cirrhosis seems reasonably clear in
             | everyday clinical practice, but how to reliably detect its
             | existence/progression/improvement/reversal to a clinical
             | trial standard of certainty is difficult and a matter of
             | dispute
             | 
             | (No I don't have cirrhosis, as far as anyone knows, but my
             | aunt had it-albeit asymptomatic, it was only discovered on
             | autopsy after she suddenly and unexpectedly died from a
             | cardiac arrest while asleep one night-which is actually
             | very common, majority of people with liver disease die from
             | heart disease before the liver disease kills them-but I do
             | have intermittent hypochondria, and in some of my past
             | hypochondriac episodes I have become rather obsessed with
             | reading papers on this and related topics.)
        
         | lokar wrote:
         | And there is nothing like kidney dialysis for the liver.
        
         | bschmidt1 wrote:
         | Goodbye fatty liver hello fatty lymph nodes! The question is
         | how often will they have to get bile drained, and what does it
         | do to body shape?
        
       | Kalanos wrote:
       | inside a lymph node is the very last place i would expect a
       | transplant.
       | 
       | they are teaming with immune cells that should be hostile to an
       | inter-species transplant. there are no red blood cells for
       | oxygen, just lymph fluid. how would it recruit blood vessels to
       | grow? it would be painful; swollen glands.
       | 
       | why not orthotopic?
        
         | sp332 wrote:
         | Years ago, someone noticed that hepatocytes injected into a
         | mouse's abdomen would migrate into the lymph nodes and start
         | making liver cells. I don't even know why they were doing that
         | in the first place, but all this research follows from that
         | observation.
        
         | Kalanos wrote:
         | teeming*
        
       | trallnag wrote:
       | Can we please grow lymph nodes and vessels next? I need them
        
         | Kalanos wrote:
         | is there no stem cell therapy/ clinical trial for this
         | condition?
        
       | idontwantthis wrote:
       | Does anyone know if they could use the patient's own liver cells
       | instead of a donor's? Is every cell in the dying liver so
       | unhealthy that they couldn't harvest any?
        
         | turblety wrote:
         | This is my thought too. How many cells are actually need to do
         | this. If it's just a few, surely if a patients kidney is in 80%
         | bad shape, then they can take a few cells from the 20% good and
         | do this?
         | 
         | I guess if there is a genetic problem with the patients own
         | liver, then it would make sense to use another persons cells.
         | 
         | Ahh just read the last paragraph:
         | 
         | > If the liver trial is successful, Gouon-Evans says, it would
         | be worth investigating whether a person's own stem cells could
         | be used to generate the cells that seed the lymph nodes. This
         | technique could create personalized cells that capture the
         | diversity of cells in the liver and don't require
         | immunosuppressive drugs, she says.
        
           | idontwantthis wrote:
           | Shoot I swear I RTFA!
        
           | caconym_ wrote:
           | This was my question too, so thanks for doing the legwork.
           | Wondering (in complete ignorance of this general topic) why
           | they didn't jump straight to that approach, though...
           | 
           | edit: I guess maybe if you start with a healthy liver, the
           | variable of whether the liver disease in question could
           | affect the viability of transplanted cells is taken out of
           | question? Presumably the immune response/immunosuppressant
           | stuff is better characterized.
        
             | jakewins wrote:
             | That last paragraph is different though, it's using stem
             | cells to make liver cells, not using the patients liver
             | cells directly..
             | 
             | I have no idea why not, but my wife does a lot of work
             | growing different cell types from stem cells, and my
             | understanding is that that's still like.. they _think_ they
             | are making cell types a, b or c, but it's a lot of
             | uncertainty. What they really do is convert the stem cells
             | into cells that express m various markers /pass various
             | tests that the "real" cell type also express.. but it's
             | really hard to know that it's actually a 1-1 match.
             | 
             | Just yesterday she was lamenting they were making astrocyte
             | cells, and many of the cells in the colony instead became..
             | something else, unclear what, maybe not even a cell type
             | that exists in humans normally?
             | 
             | Either way: using healthy liver cells from a healthy liver
             | would be a way to ensure you actually really have liver
             | cells, and not something that just sorta duck-types as one
        
       | a1o wrote:
       | > Hufford says there's reason to think that the organs won't grow
       | indefinitely in the lymph nodes. The mini organs rely on chemical
       | distress signals from the failing liver to grow; once the new
       | organs have stabilized blood filtering, they will stop growing
       | because that distress signal disappears, he says. But it's not
       | yet clear precisely how large the mini-livers will become in
       | humans, he adds.
       | 
       | Well that looks promising, hopefully they stay as mini-livers.
        
         | smeej wrote:
         | I immediately imagined people with much larger liver masses in
         | their necks and got to wondering how safe it would be. Is there
         | risk of impingement on things like arteries or the spine were
         | they to continue to grow? What's the margin of safety between
         | how big they're expected to get and how big would be dangerous?
         | (I know nearly nothing about any of the systems involved, so I
         | won't be surprised if these end up being comically naive
         | questions. I just still wonder!)
        
           | engineer_22 wrote:
           | They are using lymph nodes in the abdomen. Worth-while to
           | consider your questions though.
        
             | smeej wrote:
             | Oh you're right. I misread the part about a tube in the
             | throat and thought they were ending up in the neck.
             | 
             | Though, with lymph nodes as connected as they are, why do
             | the liver cells stay where they're planted, so to speak?
        
         | exe34 wrote:
         | It's pretty amazing, a decentralized liver. I wonder how many
         | other organs could be decentralized like this for backup.
        
           | harvie wrote:
           | Are we talking brain here?
        
             | exe34 wrote:
             | I was thinking mini-kidneys, mini-hearts? The latter might
             | involve difficult coordination, but maybe that's not
             | necessary if you've got individual hearts running at lower
             | blood pressure.
             | 
             | It all just reminds me of Neal Asher's stories, where
             | creatures build nano factories in their bodies as and when
             | needed, including local fusion "nodes".
        
               | inglor_cz wrote:
               | The people who are running this trial have similar plans
               | with mini-kidneys and mini-pancreases, yes. It is
               | mentioned at the end of the article.
               | 
               | Personally, I would like to see mini-brains. "This idea
               | comes from my ass" could become literally true.
        
       | m3kw9 wrote:
       | How does it know to stop growing up to a optimal size?
        
         | r2_pilot wrote:
         | The existing liver stops sending distress signals once the
         | stress is lessened on it, and the new liver uses the lack of
         | signal to stop growing.
        
         | fwipsy wrote:
         | This is covered in the article. As I understand it, the liver
         | grows in response to chemicals in the blood which it also
         | filters. So it will stop growing when it's large enough to
         | filter all the markers.
        
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