Successful transplant of pancreatic islets using local instead of global/long term immunosuppression

Not in humans yet, but in a large animal model and I’d expect human trials to be the next step.
TLDR- They included a microgel with the islet transplant which “resulted in robust glycemic control, sustained C-peptide levels, and graft survival in diabetic nonhuman primates for >6 months.”

Lay press article:

Full article in Science Advances:
https://www.science.org/doi/epdf/10.1126/sciadv.abm9881

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Now this is an interesting development. The use of gels to protect Beta cells from the immune system is just great.

Their method includes transferring insulin-producing pancreas cells, known as pancreatic islets, from a donor to a recipient without the need for long-term immunosuppressive medicines.

And -

“A type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on rogue immune cells, and it causes them to die,” said Yolcu, one of the study’s first authors. “Therefore, our team pioneered a technology that enabled the production of a novel form of FasL and its presentation on transplanted pancreatic islet cells or microgels to prevent being rejected by rogue cells. Following insulin-producing pancreatic islet cell transplantation, rogue cells mobilize to the graft for destruction but are eliminated by FasL engaging Fas on their surface.”

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Interesting approach. Fingers crossed. This is the type of technology solution that would be game changing.

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In 5 years??
Sorry, but even though I am type 2, I’ve been hearing the cure in 5 years for what seems like forever. This may actually be of help for those of use T2DMs with worn out Beta cells. I really don’t have much hope for dealing with genetic insulin resistance.

There has been talk of a cure for a century now. Ask the old timers here who have had T1D for 75+ years. But what’s different in this one is that it’s been succesfully employed in NHP (Non-human primates). I believe this is the first such study/research effort that has had success in NHPs. Mice, sure…but their immune system is different than humans, thus, it never translates to humans. But having success in our cousins (who share our immune system) is a huge deal.

My fingers are crossed and yes, I’m not holding my breath, but I’m very hopeful. I even told Liam about the research and he was very excited as well.

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Well the 5 years thing is totally worn out by now. The nice thing about this bit of research is a potential solution to the very difficult issue of rejection. i.e. they have been able to transplant islet cells for awhile now, but being able to make such a system work without anti-rejection drugs. Wow, that is a really tough problem to solve. And even if this implant technology doesn’t pan out, the approach will push some cool therapies forward.

As far as this solving cell uptake of insulin, of course it won’t solve that, but for the many diabetics without an insulin resistance issue, this will be a game changer whenever it gets delivered. Which wouldn’t likely be in 5 years anyway.

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I was just being snarky about the 5 year thing. This development may really be a game changer for type 1s and for some type 2s like myself. I am probably too old for such a procedure, but it would be nice to get back to dealing with insulin resistance with diet and exercise alone. I would gladly put this pump in my D drawer.

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I’d like to think this is great news for the T1s that follow our or the next generation and I hope the study and success continue. Perhaps people like those that came up with insulin and sold the patent for $1, or something like that will recur. My fear, as with many things “corporate” (sorry, I’m sure there are good ones, I just haven’t met them yet) that are run for profit, for investor dividends, or even non-profit CEO’s/similar salaries, it’s great right up to the point one of them buy the tech and suppress it because of the potential impact to their established bottom line, or the likes of a Shkrelli, be it a producer of insulin, CGM, pump, AID(s), or all of the above. Yes, I know I sound like a conspiracy theorist…but its not a lie if you believe it :upside_down_face:…or if they’re really out to get you, I mean your money :rofl:! Free enterprise is a great thing as long as there’s true competition and a choice, but it’s anathema to large corporations and survival (i.e. increased income/dividends/value) is the first law of their environment. Geez, I’m becoming more of a pessimist!

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The stuff (islet cells + bioactive microgel) was not even put into the pancreas; rather a pouch was made from the omentum (fatty layer surrounding the guts) to hold it. Apparently one of the standard ways of transplanting islet is to inject them into the portal vein upstream from the liver so that they end up embedded in the liver (those of them that survive the blood), the omental sac has been tested as a way of getting the cells in directly to a place where they can function.

The study seems to have been terminated early:

Animals were terminated with functioning grafts due to coronavirus disease 2019 (COVID-19) pandemic–associated institution-imposed logistical barriers.

The first graft was at 188 days at that point, so that’s 6 months but they had received 3 months of rapamycin. The control animals all rejected the transplant in a month (i.e. they lost glycaemic control within a month.)

Perhaps the most important thing that went unmentioned in the SciTechDaily article:

SA-FasL microgel recipients display no changes in systemic immune cell populations

Which answers the first question that occurred to me; does the microgel do bad things to the immune system in general.

The animals didn’t achieve insulin independence; the authors hypothesize that this is because they only used islet cells from a single donor each time and there simply weren’t enough. Apparently, however, the grafts seemed to function better over time when they came from closely matched animals; the one test pair they had (donor-recipient) that was completely unmatched didn’t show improvement over time. (At least that is what I understand; they didn’t explicitly state this, but the precise numbers imply it.)

They will probably have to repeat the tests to check for long-term toxicity, in particular:

We did not observe any of the reported FasL toxicity (4244), which we attribute to the form and local presentation of SA-FasL.

But with any luck that can be done on something other than NHPs.

I may be misunderstanding the article but it seemed that the technique achieved immuno-acceptance of the islet cells rather than simple immuno-suppression. I don’t know if islet cells regenerate; I assume they do but not all cells can. To me this is the most interesting part of this; immunosuppression is not necessary if the islet cells have been re-accepted as valuable parts of the cellunity.

Nevertheless if it that isn’t what is happening having an implant in a relatively accessible part of the body would be ok even if it has to be replaced every decade or so. Think pacemakers; the batteries run out and they have to be replaced.

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That right there being the biggest part of it!
Not that I’m holding my breath. But I know I would have a surgery every 10 years if that is all it took!

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Yeah, well don’t quote me, oh… ok you did, but it’s all down to the Treg stuff in the paper, e.g:

https://www.science.org/doi/10.1126/sciadv.abm9881#F1

and I may be completely misunderstanding that. That said I’m with you on the 10 years. 10 years insulin delivered in one operation of, I think, less complexity than replacing a pacemaker.

Neat. Medicare will probably have been limited to farting, dyspepsia and aphrodysia, but maybe I can get my insulin replaced…

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Ok, I went through and READ that article.
And yes, they flat out said that it establishes immune acceptance.

"“This finding is in agreement with studies in diabetic mice demonstrating a pivotal role for Tregs in establishing SA-FasL microgel–induced immune acceptance”"

Obviously 177 days is not evidence of a truly prolonged success, but I think, that in the NHPs over a short duration, they definitely succeeded!
And to be highlighted, these are NHP, not mice. All the testing on mice is basically just a giant tease to us all, as they create such high false hopes it isn’t even funny any more…

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That’s great news. Maybe this time it will BE “just 10 more years”. Or not.

This solves part of the problem. Next they need to get through human trials.
After that, there aren’t nearly enough human donor pancreatic islet cells for more than a few thousand subjects -without matching… Cloning/genetic engineering of individual candidate’s T-cells will be needed to produce enough, closely matched to that individual.

For that to happen, political/religious resistance will need to be overcome, with the USA being the toughest opposition. And if cloning is only done by specialty labs outside the USA, the cost of getting an implant won’t be affordable.

No one wants this to happen more than I do. I haven’t got 20 years. The only way I see it happening in 10, is if it’s shown within 5 in Europe to be significantly cheaper than the cost of maintenance.

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It wouldn’t need to be cheap honestly, if it worked as we expect a normal pancreas to work, then it would reduce hospitalizations and deaths significantly in the treatment arm, and would be able to pass the financial hurdles pretty easily. Diabetes is an expensive disease, so even if the treatment is expensive it would be hard to not show a huge favorable improvement, as long as patient selection was paid attention to.

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I didn’t say cheap. I said cheaper than maintenance. Maintenance is the cost of supporting a person with diabetes for their lifetime.

Insurance companies would be the determining factor for a relatively expensive ( in comparison to feeding family of four for a year) procedure.

Insurance companies,with very few exceptions,fo everything based on cost. If they can pay $5,000 a year for the average expected lifetime of a person with diabetes instead of paying $100,000 today they’ll pay the $5,000 per year.

Before you nitpick over this I know it costs more than $5,000 on average but the principal holds.

The value of money in hand today to an insurance company is worth 10 times it’s face value over 30 years because they make money lending their surplus money out. Also, few people stay with one medical insurance company for a lifetime.

Btw, this is also true of Medicare . The federal government borrows every year and pays interest on what it has to spend this year that it can’t cover. Currently Medicare is spending more than it’s taking in and in less than 10 years the shortfall will have to be made up one way or another. Since there’s a limited amount of money and taxpayers pockets if it gets taken out for Medicare it’s not available for other care.

If it weren’t for the high cost of end-of-life care it’s doubtful whether it would be so easy for some of us to get Medicare to pay for insulin pumps.

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I understand what you are saying, the maintenance is just the tip of the iceberg in the costs. The actual additional care a diabetic gets, pales in comparison to the maintenance of the insulins, and the CGMs etc. The increased risk of cardiovascular disease, the amputations, the kidney transplants, etc would all be added into the maintenance. It really is quite a high number and well above the cost of just keeping a diabetic going.

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You don’t understand . You’re looking at it from an individual standpoint. I’m explaining actual costs to others which I’m very well aware of.

All the things that you list that actually happen are part of the health care cost of maintaining the life of a person due to diabetes.

Some of those costs are paid by others.

The figures that you’re most familiar with are prices, not costs. The skyrocketing figures that are trumpeted in the news media are prices. No insurer pays list prices. No insurer pays for everything. Every insurer pays for as little as they can.

In the US both private and public coverage have lifetime caps. The cost of facilities and staff for health care are fixed costs. They don’t vary with the number of customers. What varies is revenue and how much profit they make per dollar of fixed cost.

I hate it but from their cost perspective it would be better if we simply died sooner and suffered the same personal consequences for fewer years.

The list prices that are charged to uninsured people for services vary from 2 to 10 times what insurance companies pay, with Medicare in many cases paying the lowest for those services.

What is not part of their costs is lost years of productivity. There are more people than necessary to provide all the goods and services for those people. That’s why governments encourage their citizens not to conserve but to consume.

It’s only with things like pandemics when the cost of providing prevention temporarily becomes more important (but not cheaper than care ) because healthcare capacity is exceeded and everyone starts complaining.

Covid was a windfall for profit based hospitals. A hospital is most most profitable when it’s facilities are used close to capacity.

Doctors whose schedules are so full that they can only see patients every 4 to 6 months are more profitable than when they are able to see them every 3.

As I originally stated in words that you did not understand , only if the cost to others of providing transplants for all with diabetes is less than the cost to others of keeping us alive during the same length of timr with other treatments will there be a financial incentive for those insurers to provide an alternative treatment.

I fully understood what you said, I just disagree. I have been part of a team gaining insurance coverage for a very expensive treatment, that wasn’t covered prior to putting our product on the market. If you have favorable cost per life year saved data, you can get insurers to cover a treatment even if it costs more than the maintenance. Especially if it improves the quality of life scores of the patients in the study, which this treatment certainly would.

edit - also the pricing strategy the company undertook would absolutely take insurance coverage (by country) into account when they roll the product out.

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I understand what you are saying. I wish I could agree.

I’d like this to reach the market with encouragement instead of opposition every step of the way, but I’ve too much experience to think that will happen. I also know that there is no way that I can convince an optimist to change his feelings with words. Nor do I want to. We need optimists. I need them more than ever before.

I can’t agree or disagree with a viewpoint based on generalizing from a specific or using a non-objective metrics like quality of life in a discussion of economics. I don’t think that way; I’m a realist… I only know that the only way for any force to prevail is if it is powerful enough to overcome inertia and opposing forces.I understand that there are many powerful opposing forces at work here. Economics is the last one I mentioned, but it is the best organized and will have a direct effect on religion and politics. People as whole aren’t altrustic or sane. They are selfish and emotional, vote with their wallets for their personal interests. Progress is made by the atypical, fanatics, mad-people with missions.

I need optimists to focus on the goals- a cure and prevention- and continue to apply pressure where it will be the most effective as my ability to do so from desperate stubbornness diminishes. I don’t expect this to benefit me, but maybe my descendents.

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