Like I notice there is a huge push for prevention, which is fantastic, but that kind of feels like taking all the people who are already suffering from intractable conditions and throwing them under the bus.

Like when are we gonna actually get lab grown kidneys, livers, tendons, and all that shit that would immediately help so many people? I remember at the beginning of this century stem cells were all the rage, but I haven't seen anything groundbreaking. Every "promising" study said that treatments (perhaps cures) were "5 to 10 years" away.

We can send a probe to the south pole of the moon but if you have back pain then it's basically "fuck you here's some pain meds but we're not gonna actually fix your issue... maybe try to do some physical therapy and get out of my office" kind of shit. Or "You got diabetes? too bad no cure here's some $8k insulin." And "Oh you tore your miniscus? Well just 'take it easy' and do some leg exercises and I'll do some surgery on it, but it'll never be back to 100% so get the fuck out of my office and here's a bill for $3k." Or "oh it seems you have carpal tunnel and some tendon/ligament damage... i guess you could do some surgey and some 'hand exercises' but it'll never be the same as it was before, oh btw here's a bill for $5k."

Even something not as critical like hair loss (which is psychologically damaging for men and especially so for women) still relies on the good old "go to Turkey to get a hair transplant. oh you want to actually grow your original hair back? too bad, even though we should have figured out that shit using stem cells by now."

That's not even mentioning the people suffering from things like chronic fatigue or long covid. They are basically tossed aside like a bad batch of vegetables. "oh yeah this batch is fucked, oh well maybe better luck with the next batch!"

I know I'm just venting here, but what's the fucking deal? Are we actually going to have legit regenerative medicine? Or will it always be "5 to 10 years away" for the rest of eternity?

  • appel@whiskers.bim.boats
    ·
    edit-2
    10 months ago

    I agree with what everyone else also said. Capitalism itself is definitely a huge issue. Making cures for things is not profitable (if the notion of a "cure" exists at all). For one of your examples, diabetes, this could be solved as you rightly imply with stem cell treatment. It would certainly be expensive, but a transplantation of pancreatic islet cells could theoretically cure type 1 diabetes by replacing the missing cells. There are several research groups working on exactly this, however there are some challenges. This paper (open access) provides a good overview of the current approaches.

    Firstly, the cause of type 1 diabetes is often due to auto-immunity, that is, the persons own immune system is attacking and destroying their cells that would have produced insulin (pancreatic islet cells). This is a problem, because even if you had managed to create a perfect pancreatic islet cell population (will explain later), when you implant it, their immune system will just destroy them again. Recent research is trying to use some kind of capsule to protect the cells from the immune system, but still allow insulin secretion. They are evaluating different capsule materials for longevity and biocompatibility. Secondly, producing the cells themselves is relatively difficult. in 2014, Pagliuca et al(open access) achieved this, fully in vitro (in glass; in the lab) from human induced pluripotent stem cells (iPSCs). Other approaches considered using embryonic stem cells (ethical no no for obvious reasons) or just taking cadaveric islets (islet cells from recently deceased). iPSCs have similar differentiation capability to embryonic stem cells, but can be made from the persons own cells. The process roughly looks like this:

    • take somatic (body) stem cells from patient
    • treat with Yamanaka factors to turn into iPSC
    • expand (grow) the cell population in vitro using cell culture techniques
    • treat with various transcription factors and other ingredients (vitamins, etc, full list in the Pagliuca paper) over a time period
    • voila, now you have insulin secreting cells derived from the patient themself, no risk of immune rejection (but they still need to be protected from the patient's autoimmune disorder which causes the diabetes in the first place).

    This process probably takes at least 3 months (Don't know exactly, I'm guessing from knowledge of other cell culture experience), and requires specialist knowledge and equipment. However, there do exist automated cell culture systems that could potentially achieve this, but I think they can only do plate-scale, which is still too small to create enough cells.

    You can see from the academic papers, looking at the other papers they cite, that the time between these publications is quite long, often 5 years or so. Some of the papers cited are pre-2000s. Each of these papers requires a lot of work and time from these research groups, and each publication probably takes around 5 years. Biology is a pretty slow moving science, it is necessarily highly experimental and manual, experiments have low chances of success, take a long time, ethical approval takes a long time etc. etc.

    Of course, if big pharma wanted to make a stem cell therapy happen for diabetes they absolutely could, they probably could have sorted it out a few years ago. It would require an automated cell culturing system to create the islet cells, fed with the right reagents, which themselves would have to be produced by precision fermentation (another advanced and expensive process). This would probably be a huge box that hospitals or treatment centers would have to buy, and then they would take patient samples, grow up the cells, and then reimplant the cells into the patient after a few months. The patient would probably be insulin independent for a very long time ( I don't know what the current expected longevity of the treatment is, but at least a few years). If they wanted to, they could overcome all of these challenges with their enormous funding. They could make this work much faster than the various academic groups around the world can. They already have experience of biological supply chains, building machines and regulatory approval. But how much would this project cost them? probably in the order of 10s of billions (antibiotics, which are comparatively simple, take around 2 billion usd to develop). That is a lot of capital expenditure for a cure, where instead, they could just keep charging you an arbitrary amount of money for regular insulin, which is a process that has been perfected ages ago. And this is why we are in this situation. It is simply not economical for big pharma to pursue "cures" because of the high initial cost, and it cuts off a potential revenue stream of a patient who has to keep coming back for more insulin, drugs, whatever.

    The second thing I want to talk about is the idea of whole (internal) organ transplants (skin is relatively easy iirc), made by stem cells. This is exceedingly difficult to achieve, and any news article that says they are just 5 years away is lying. The main reason this is so difficult is because we have to effectively try and replicate the conditions inside the womb. We have to know exactly which chemical signals are supplied to the developing organ at exactly which time, by the myriad of different cells that also exist next to that organ. Organs do not develop in isolation, the animal foetus is an extremely complex signalling system where almost all of the different components are in some way related and influence each other's development. There is some progress with different approaches like 3d-printed scaffolds Of course there is the "easy" option, which is growing human-like organs in other animals, most likely pigs. Personally this doesn't sit right with me, to create human-pig chimaeric animals and then slaughter them, just so that we can live a bit longer.

    In conclusion, it's down to the following reasons:

    • Media is always overblown
    • this is very difficult science, and it is generally only carried out by academics, and does not receive much industry funding because:
    • big pharma doesn't want to cure you, they just want to keep selling you profitable subscription treatments.
    • all because of capitalism.
      • appel@whiskers.bim.boats
        ·
        10 months ago

        Unfortunately you can't genetically engineer the patients immune system when they are older than an embryo. You would have to take out and modify every cell in the body that is involved in immune function, which is not feasible. If this was possible, you wouldn't need the new pancreas in the first place.

        Yep, 3d printed scaffolds for certain organs might work, most likely the morphologically simpler organs like the pancreas and the liver (basically just blobs), but the challenge is still how to grow blood vessels in there and how to make sure they have the right tubes. Creating a scaffold for something like the heart, and correctly seeding all of the different tissues is more difficult.

          • appel@whiskers.bim.boats
            ·
            10 months ago

            That involves taking the cells out of the patients body, then modifying them, growing more of them, and then reimplanting them. (autologous CAR T Cell therapy) Only these cells that have been reimplanted will be modified. This is ok for adding a target, like the cancer cells, but for removing a target, it doesn't really work. The immune cells in the rest of the body ( they are very distributed) would then still attack the target, which is why it doesn't really work for treating diabetes. It does make me wonder though, if you could remove and edit all of the stem cell populations that feed the immune cells, then every future immune cell would be modified. However this would probably require many surgeries all over your body. "Immune cells" as I have referred to them also do not really exist, the immune system is made up of many different types of cells, all developing in different parts of the body.