Stem cell research: Is the US in danger of falling hopelessly behind?

Great Debates
61

It depends entirely on what the medical industry is able to do.

As I’ve said in my earlier posts we have already successfully treated people with stem cells, in fact we have been doing so for years, decades in fact. Allogenic and autologous stem cell treatment has been going on for a very long time.

If diabetes mellitus can be treated allogenically or autologously then ultimately it would be as simple as transplanting stem cells from a donor pancreas.

For example it is becoming more and more common that people with bone marrow cancer receive enough radiation to complete destroy the affected bone marrow. Then, they receive a translpant of bone marrow stem cells either from a donor or from themselves and it effectively restores the loss bone marrow, obviously without the cancerous growth.

Unfortunately that is probably never going to be a possibility with diabetes because there is more at play.

Type I diabetes is actually an autoimmune disorder. This means that for whatever reasons some time ago your body, for reasons unknown to anyone at this time, started attacking your pancreas. In short order the ability of your pancreas to produce insulin was destroyed almost completely or completely.

Luckily it appears that this autoimmune event is not a permanent one (to answer your first question, something triggered your immune system, and your pancreas was attacked, but it doesn’t appear this attack is constant and it hasn’t attacked the successfully transplanted pancreas’ of diabetes patients). Which means if you were to receive a pancreas transplant, you would no longer have diabetes and the autoimmune incident that ruined your old pancreas wouldn’t happen again, at least that is the case with all known pancreas transplants for the purpose of treating type I diabetes.

You’re probably thinking a pancreas transplant sounds bad, and it is, but probably even worse than you would expect.

Firstly, 20% of the people who receive them die within two years. Now, the only diabetics doctors even perform the operation on are people who have already been the victim of other very severe symptoms because of diabetes (kidney failure for example) so the risk had to be taken or survival would have been very difficult.

Unfortunately on top of that, 50% of all pancreas transplants are rejected, which means your body destroys the new pancreas thinking it is a foreign agent, and you have type I diabetes again.

And on top of THAT you have to take a lot of immunosuppressive medication to receive a transplant, and that is also a huge health risk.

So right now the only way that stem cells could help you is if there is a process developed which will allow a fully new pancreas to grow and be transplanted in you or if there was some way to repair the tissue damaged by the attack.

There is a problem, though.

The treatment would have the advantage that your pancreas was being “cloned” which means that there wouldn’t be nearly as much chance of rejection.

However, since the root cause of diabetes (type I and II) is unknown, it may very well be possible that something in your genetic makeup caused you to be born with a pancreas that set off your immune system. So a cloned pancreas may set off the immune system yet again, and you could not live on immunosuppressant therapy for the rest of your life. However, that is just speculation. Hopefully type I diabetes is caused by some unfortunate random incident that is unrelated to the genetics behind your pancreas.

Here’s why this treatment is so far off:

  1. Doctors have to find a medium to put organs on to grow them, this is a huge problem across the spectrum with stem cell research. Biologists are still looking for a “pallet” to grow organs on successfully, I’ve seen some research recently that showed a lot of promise.

But I’ve seen that in the past, so I won’t get your hopes up here without cause.

  1. Doctors have to figure out how to make your pancreatic stem cells grow into a new pancreas, we’re getting into areas I don’t know much about, but I’m not sure that this is possible using pancreatic cells. Growing a fully new pancreas may only be possible via totipotent stem cells only found in the embryonic stage of human life.

  2. If 2 is true, then doctors have not learned how to reliably trigger totipotent stem cells into growing into specifically what they want.

  3. All research so far that has involved stem cells growing into things has resulted in failure (AFAIK). Cells start reproducing, but ultimately something goes wrong along the way that messes it up. Maybe lab error, maybe something else, this is a huge hurdle.

As far as repairing damaged tissue, stem cells have had mixed results in this area. For example stem cells have repaired damaged heart cells, but the problem seems to only be fixed briefly then the whole thing quits working.

Anyways, diabetes is a serious disease. Roughly 200,000 people in the United States die every year due to diabetes complications.

However, unfortunately many of these people died because they were not religious enough or consistent enough in treating themselves. Treating diabetes requires a great deal of personal discipline, every day, all day, for the rest of your life.

There was a study conducted in the early 80s the Diabetic Control and Complications Trial (DCCT) was conducted. The trial ultimately showed that 75% of the complications that result from diabetes can be avoided if the patient strictly follows a treatment regimen.

62

If you want a time estimate 20 years is being generous. Probably 30 years.

Even if we found the treatment tomorrow it would be in clinical trial for 10 years before it was opened to the public.

63

[QUOTE=Martin Hyde]
It depends entirely on what the medical industry is able to do.

Type I diabetes is actually an autoimmune disorder. This means that for whatever reasons some time ago your body, for reasons unknown to anyone at this time, started attacking your pancreas. In short order the ability of your pancreas to produce insulin was destroyed almost completely or completely.*

Two things here:

  1. I’m one of those funky LADA diabetics so I have the advantage that it is significantly slower in its progression. For a typical child diagnosed with T1D (type 1 diabetes, but I don’t want to type it out 30 times) they go from onset to having no islet cells (our friends who make insulin) in about 6 months. People diagnosed over the age of 30 with T1D (not T2D – that’s important) can often maintain some insulin production for years. I was diagnosed almost 8 months ago and I’m still taking about 1/10th the amount of insulin required by the a typical “fully baked” T1D.

  2. My body ONLY started attacking one part of my pancreas. It started killing off the islet cells. The other functions of the pancreas (Hell, I don’t know much what they are since I don’t have to take over those jobs for it) are unaffected. The organ itself is fine. It’s missing islet cells (or, in my case missing a sufficient number of them) only.
    *Which means if you were to receive a pancreas transplant, you would no longer have diabetes and the autoimmune incident that ruined your old pancreas wouldn’t happen again, at least that is the case with all known pancreas transplants for the purpose of treating type I diabetes.

You’re probably thinking a pancreas transplant sounds bad, and it is, but probably even worse than you would expect.

<snip>

So right now the only way that stem cells could help you is if there is a process developed which will allow a fully new pancreas to grow and be transplanted in you or if there was some way to repair the tissue damaged by the attack.*

Indeed, it’s quite bad. But also <shrug>, over-kill. The more promising transplants these days are the ones being done in Canada where they transplant ONLY the islet cells. They have to harvest way more than the amount found in one donor pancreas and they’re still playing around with where to transplant them (maybe the pancreas, maybe the liver!). The downside is that you still have to take the anti-rejection drugs.

Which brings to mind the promise of stem cells, no? Why grow a whole new pancreas when I only really need a tablespoon or so off islet cells. One type of cell, not a whole organ.

*However, since the root cause of diabetes (type I and II) is unknown, it may very well be possible that something in your genetic makeup caused you to be born with a pancreas that set off your immune system. So a cloned pancreas may set off the immune system yet again, and you could not live on immunosuppressant therapy for the rest of your life. However, that is just speculation. *

Even if it’s good speculation, for someone like me with the LADA T1D, it could be the difference between taking 3 shots a day (to say nothing of 6-12 blood glucose tests) and going in once every 10 years to have a long needle proceedure that gives me a “refil” that my body can then start nibbling away on. Again, this would be much more of a drag for a 10 year old whose body gobbles islet cells every 6 months.

As far as repairing damaged tissue, stem cells have had mixed results in this area. For example stem cells have repaired damaged heart cells, but the problem seems to only be fixed briefly then the whole thing quits working.

What about taking some of my remaining islet cells and using them to “grow” new ones using the stem cells as . . . canvas? Or am I dreaming there?

However, unfortunately many of these people died because they were not religious enough or consistent enough in treating themselves. Treating diabetes requires a great deal of personal discipline, every day, all day, for the rest of your life.

I’ll (narrowly) resist getting pulled into that one. I hear from lots of folks how doable maintaining diabetes is. Most of those folks aren’t doing it. When I was diagnosed, I took it on the same way that I would have taken on a whole second job. I quit grad school so that I would have time to pour through book after book and troll the internet and go from one doctor to another reviewing and then working out gameplans for reversing the (in my case, all short-term) damage that the elevated sugars had already caused before I was even diagnosed. I learned to take a needle and stick it into my body even when it hurt or bled and even when I was crying and even on days when I really didn’t have it in me to do it. I didn’t eat when I was hungry, ate things I didn’t want other times and (believe me this was the one that made me the maddest) ate without tasting when I wasn’t hungry. I stopped exercising to be the strongest woman skater in my small town and changed my routines to be the ones that were the most pleasing to my diabetes.

My A1C is under 6.5, hell, it’s under 6.0 (gotta love the T1D “honeymoon phase”)but it’s more than just a little work.

I can understand why some people would decide that it’s not worth the pain.

Ok, looks like I didn’t resist the getting pulled into that one too well. Mea Culpa. What can I say, I’m a fussy newly-diagnosed diabetic :wink:

64

Alice,

**Martin ** does not know of which he speaks.

I actually do islet cell transplants for a living. Well not the transplant itself, that’s done by an Interventional Radiologist, I do all of the research and the cell isolation and release testing. There are dozens of centers around the US and Canada including mine that are currently doing human trials on cadaveric Human Islet Cells. The process should be approved later this year, or early next. DRI in Miami has very promising results with embryonic stem cell, and says they will be ready for human studies in five years.

Check out this site: www.insulin-free.com, or e-mail me at thielka1 at hotmail dot com for further information.

65

I didn’t speak about anything I didn’t know. That’s why I did not even mention islet transplantations, I’ve never heard of them.

I tried to keep my discussion strictly to stem cell treatment for diabetes. And I explained the problems with stem cell treatment and the problems found with other types of stem cell treatments when you start trying to grow things with them.

Your solution (islet transplantation) has nothing to do with stem cells, nor either do pancreas transplants.

But I can assure you everything I said was factual, although perhaps not complete.

66

[QUOTE=Alice M.]
*

That’s probably why I referred to it as, “a great deal of personal discipline, every day, all day, for the rest of your life.” And not a “little work.”

Probably 10 years ago I had an aunt diagnosed with type II diabetes, she was in her early 50s IIRC. She took her meds but that was about it, she ate just like she did before and was in and out of hospitals for 3-4 years and did some pretty serious damage to herself. Eventually she died.

It was a sad case of someone not taking care of themselves and not doing what was necessary to keep themselves alive.

No one is saying diabetes is easy or trying to say diabetics only become sick because they are lazy and don’t manage their condition properly.

Personally I’ve been on a strictly managed food plan for 10+ years, I eat roughly the same thing every day of my life. Now, I don’t do it because I have to, but I do it because I’m a serious body builder and one cannot sculpt their body without the proper nutriton.

It’s not the same thing as having a life threatening illness, but I do remember how hard it is to carefully monitor every morsel that you consume when you first start doing it.

67

Martin, may I ask what your academic/professional background is? You seem to have a lot of specialist knowledge in various subjects.

68

One of the most difficult periods of coming to cope with my son’s diabetes at his onset for my wife and I was when we listened to people who had no idea what they were talking about. One woman had us believing that we would essentially have to make most of his food from scratch, and that he would be living almost a boy in a bubble kind of existence. Speaking authoritatively on topics such as these without a knowledge base can be quite harmful.

69

Thank you for the link, light strand. I guess I’m still curious about the exact way that stem cells would be used for Type 1 Diabetics (I’m only leaving out Type 2 Diabetics becuase I don’t know enough about their disease). Would they need to have some of my islet cells and then “copy” them with the stem cells?

Could you please explain how it would work?

70

[QUOTE=Martin Hyde]
That’s probably why I referred to it as, “a great deal of personal discipline, every day, all day, for the rest of your life.” And not a “little work.” *

The emphasis on “a little work” was yours. I wasn’t quoting you, I was using understatement for emphasis. I’m from the south. We talk that way.

*Probably 10 years ago I had an aunt diagnosed with type II diabetes, she was in her early 50s IIRC. She took her meds but that was about it, she ate just like she did before and was in and out of hospitals for 3-4 years and did some pretty serious damage to herself. Eventually she died. *

That sort of thing is very frightening for me. You’d be surprised how many folks have stories like that (and, believe me they all came out of the woodwork wanting to tell them when I was diagnosed with diabetes). But, at the same time I have to consider the other side. Do I want to never eat the foods that I used to enjoy so much. Or only eat them as medicine of sorts (using them as a treatment when I have an insulin reaction – I assure you, these are not times when I can really enjoy what I eat)? For that matter, do I want Diabetes to be the most imortant thing I do every day. Basically, I know the answer is, “No.” I’m starting grad school back up in a few weeks. I need purpose and, for me anyway, focusing every day on keeping the wolf away from the door isn’t energizing the way that moving towards something is.

*No one is saying diabetes is easy or trying to say diabetics only become sick because they are lazy and don’t manage their condition properly. *

Actually, lots of folks say precisely this. But they mostly say it with regards to Type 2 Diabetics. I hear it all the time. People feel free to open up with both barrels around me because I didn’t, “do it to myself”. From what I’ve seen, the genetic component of Type 2 is very hard to avoid. Every Type 2 I know had it running in their family. Type 1 is sneakier (obviously, still genetic) and I’m the first one I know of in my family on either side.

  • It’s not the same thing as having a life threatening illness, but I do remember how hard it is to carefully monitor every morsel that you consume when you first start doing it.*

Some people, lots and lots of them, don’t have this in them. I’m an athlete too so I already knew how to tune my body to a certain degree (man, have I learned a lot in these last 8 months!). But if I had not already been athletic it would have been very difficult to start an exercise program while I already felt ill. Even beyond that, food discipline is simply beyond what some can do. We know that because of the rates of obesity that aren’t affected by one diet craze after another. <shrug>

Discipline may be an answer, but it also might not be one that is accessible to most.

71

Yes, Hentor. I met those people in droves. As one friend of mine who is Type 1 Diabetic said, “When you’re diabetic, everyone thinks they’re your mother.” I think this is especially difficult to deal with as an adult coming down with the child’s disease (what were the odds? damn slim). And, you hear the same misinformation over and over again (“It’s because you’re vegetarian” “Gosh, that shouldn’t have happened to you, you’re so THIN” “Oh, that’s reversible with this diet I heard about . . .”). But, annoying as that has been, I’ve also been absolutely heart-broken by the kindness that people have poured upon me since my diagnosis. I’ve never experienced anything in my life like that, and I feel . . . fortunate.

72

Howard Hughes has a research institute that, among other things, is into stem cell research.

The US may, as a matter of policy, be behind the times, but I doubt there would be any problem with US scientists working with foreign scientists. There’s no olympic medal for discovering a way to make paraplegics walk again. It would be nice if mankind could win it for mankind (although there’s bound to be some schmuck, like in the AIDS research, that’s looking for glory).

73

Ah Mr. Hyde, so many errorrs, so little time.

I’m not sure how you’ve divined this. If this is what he thought he was doing then he’s even dumber than I’d believed him to be. If he wanted to ban the use of fetal stem cells, than he should have just banned fetal cell use. However, since this is not what he did, than I have to believe that he is against the use of stem cells from IVF.

Manufacturers rarely do pure research. Almost every biopharmaceutical had its beginnings in a university, and thus federally funded. Every major breakthrough in Biology, and I would hazard a guess to say in science in general, can find its beginning in academia.

This is why we are very much in danger of falling behind

In addition with (the commonly quoted number) 400,000 embryos from IFV currently waiting to be destroyed the use of aborted fetuses will be limited.

Um, no. The most promising are embryonic stem cells, that’s the crux of the entire debate.

I’m going to ask for a cite on this. There had been some results in getting adult cells to differentiate between related cell types, but noting even close to a skin cell becoming a neural cell.

Most of these procedures are complex. For crying out loud, you should have run a PCR ten years ago. There were about eleventy million steps, it cost a fortune, and there were about fifteen thousand way to screw it up. Now it’s a kit. There can be no advancement, without a beginning.

How are you getting this? First of all, although it is autoimmune, it doesn’t attack the pancreas, it attacks the islet cells. Type 1 is genetic, permanent, there’s no telling what would happen in a pancreas transplant alone (PTA)

Your numbers are off. The success depends on if you get a Pancreas alone, or a pancreas with a kidney, either after (PAK) or simultaneous (SPK). Without going into crazy detail, the most recent data suggests that technical failure rate is approximately 8% for KP, 13 % for PAK, and 11% for PTA. Graft thrombosis (mainly venous) occurs in 2-14% of cases resulting in early graft loss. For PTA, the rejection rate is about 30% with 10% graft loss. Graft survival nationwide, as recorded by UNOS, is 88.5% at 3 months, 80% at one year, 52.9% at 3 years and 40.7% at 5 years. Results are better with kidney-pancreas transplants (87.7%, 83.8%, 77.2% and 67.5%, respectively). During a ten-year period (1991-2000), the annual death rate range was 36.3 to 82.3 per 1000 patients for pancreas transplants and 31.1 to 63.2 per 1000 patients with kidney-pancreas transplants.

Islet cells grow in a relatively standard culture medium (with modification) Since they aren’t “tissue” in the strictest sense we don’t have too much problem growing in a standard T-175 culture flask in a CO[sub]2[/sub] incubator.

Nope. Whole organ isn’t the goal. Replacing dead cells with live one derived from stem cells is the goal. Stem cells to other cells is relatively academic. Getting those cells to do what you want them to do, when you want them to do it is the hard part.

it’s already done.

Nope. Lots of labs are doing this.

This is utter bullshit.

This is wrong. DCCT was testing between two types of treatment, not a treatment and a control. From the DCCT website: ” The study compared the effects of two treatment regimens–standard therapy and intensive control–on the complications of diabetes. Volunteers were randomly assigned to each treatment group.”

I would estimate 5 for development, less than 5 for trials. But that’s just me, and I know what I’m talking about

I can assure you, that very little of what you said was factual, or complete.

74

Alice,
What we are doing currently is; we get a pancreas from a cadaver. However, we are low priority, because whole organ gets first pick, so often the organs offered arena’t suitable. But if they are, we start to isolate the islets.

Basically we mash up the organ first chemically, by digestion, and then mechanically. After a while we get an islet/pancreatic (acinar) tissue mush. Then we purify the islets, and remove the acinar tissue.

Then, if our yield is good, we transplant the islets into the liver of a living recipient via the portal vein.

We are immediately losing 50% of infused islets through recipient immune response, despite heavy doses of immunosupression. Eventually we lose all of the islets, and in two years the recipient needs another transplant.

The promise of stem cells for islet cells is first: a constant source of cells. Currently a successful Islet cell transplant is taking two cadaveric organs. This number is quickly coming down, and we have quite a few centers who can do it in one, after culturing the islets.

The other big problem is the eventual loss of cells to immune response. My lab is currently trying to figure out what the immune system is attacking. We think we may have a good idea. If we can get this nailed down, we could genetically induce the Stem cells, not to produce this protein (it’s not require for insulin production) and therefore, you could hopefully go without the immunosupressants, because the cells also wouldn’t be type specific.

If these two things happen, and it is my belief they will, stem sells will “cure” diabetes mellitus type 1.

75

[QUOTE=light strand]
Alice,
We are immediately losing 50% of infused islets through recipient immune response, despite heavy doses of immunosupression. Eventually we lose all of the islets, and in two years the recipient needs another transplant. *

Is this the same immune response that was causing the diabetes in the first place or the response from the fact that the cells came from a foreign pancreas?

Since the initial destruction of native islet cells is so much slower with LADAs, might (assuming the former above) the time between islet loading and islet depletion be longer for them? This would, of course, depend heavily upon the people who are being selected for the studies, I suppose.

The other big problem is the eventual loss of cells to immune response. My lab is currently trying to figure out what the immune system is attacking. We think we may have a good idea. If we can get this nailed down, we could genetically induce the Stem cells, not to produce this protein (it’s not require for insulin production) and therefore, you could hopefully go without the immunosupressants, because the cells also wouldn’t be type specific.

What is the time frame for the stem cell “fix”? You said about 10 years for the islet transplants to be approved, how much longer for stem cell transplants (infusions?)?