[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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