Stem Cell Cure for Diabetic Mice, Suicide Genes, etc.

Lots of buzz last week about that exciting development in stem cell therapy: Novocell researchers in San Diego, CA, managed to control diabetes in mice using human embryonic stem cells. A first! Validating the concept that embryonic stem cells can be coaxed into becoming insulin-producing islet cells right inside a living organism — rather than simply in a petri dish.

Stem_cells_pancreas_2

So how far off are we, really, from making this happen in humans?

Yesterday I was privileged to have a long talk with Dr. Camillo Ricordi, director of the Diabetes Research Institute in Miami, FL, who’s quoted in the New York Times coverage. He was actually a bit exasperated that he’d spent such a chunk of his time on the phone with the NYT reporter, explaining all the workings of the science, only to find himself quoted in one single sentence: “For those who say there is not much evidence that embryonic stems cells can cure diabetes, there you go.”

Well, he got a chance to explain a whole lot more to me:

THE RISKS

As the NYT notes, the FDA may be hesitant to approve trying this therapy in humans because it involves injecting people with “early-stage” cells that have yet to “mature” in the body.

“Once you put these cells in vivo they can grow in any direction. In this study, there was also a tendency toward hypoglycemia. Maybe the cells will have ‘shutdown problems.’ Glucose levels in the 40s and 50s are of course not good,” Ricordi says.

There’s also that issue of developing tumors, which some of the mice did. Ricordi says the risk is 15%, which sounds far too high for most patients’ taste, I’d imagine.

ROADBLOCKS & ALTERNATIVES

Just a few days before Novocell’s announcement, Dr. Douglas Melton’s stem cell group at Harvard published a paper in which they were able to “map human embryonic stem cells for differentiation,” Ricordi says. This means they used screening tools to show that only a very few have the potential to become insulin-producing pancreatic cells.

This explains why others have not had success curing diabetes in mice using similar protocols; they simply weren’t using the right stem cell lines, according to Ricordi. But the right stem cell lines are going to be very hard to come by.

“With only 6,000 donors a year, and only half of those suitable for this use, you could cure a max of 3,000 patients a year at best. But who’s going to pay for this? Once this treatment became available without the need for lifelong immuno-suppressant drugs, it would become like the lottery — everybody would want it. We don’t want this to be some privilege restricted only to the wealthy.”

He also says that human islet transplantation will be widely available much earlier than stem cell therapy. Islet transplantation from a healthy pancreas source is already in Phase 3 trials for FDA approval, he says.

WORK-AROUNDS

The big issue with islet cell transplantation — and stem cell, too, when it’s ready — is the need for immuno-supressing drugs that keep the body from rejecting the implanted material. These drugs have proven toxic to the implanted cells. “They block the capability of the cells to replenish themselves, to regenerate… but we’ve changed the mix of drugs, using a different combo of drugs that have less effect on the cells ability to replenish themselves,” Ricordi says.

For stem cell treatment, Ricordi and the DRI are working on another option to eliminate the risk of the cells developing into tumors or other unwanted material in the body. They’re developing so-called “suicide genes.” They would use genetic engineering to pre-program genes to self-destruct in case they don’t develop in a certain way. Pretty neat! The genes that go bad would just automatically commit suicide. Sound far-fetched? Scientists have been working on it for cancer therapy for at least a decade.

BOTTOM LINE

In any case, the Novocell announcement is exciting to the science world, and therefore to us, at a very fundamental level. “Before, there was no evidence that stem cells can cure anything,” Ricordi says. “Hopefully the lessons we’ve learned from islet transplantations will help in this effort.”

Thank you, Dr. R, and a huge thanks to the DRI for the work you all do!

Advertisement

12 Responses

  1. Mark
    Mark February 27, 2008 at 8:32 am | | Reply

    A huge thanks to all in the science world wherever they are when it comes to trying to find a cure. Too bad politics and religion have to intervene.

  2. Rob
    Rob February 27, 2008 at 8:36 am | | Reply

    Ok – great, they might be able to treat a few patients but 15% of them are going to get cancer. Why is this newsworthy?

    Meanwhile, LCT in New Zealand is in Phase I/II testing on ACTUAL HUMAN PATIENTS with islet replacement therapy using encapsulated porcine islets. As far as I can tell from what they’re publishing, the patients are performing better than expected and are all off of insulin. This is without immunosuppression mind you.

    http://biz.yahoo.com/iw/080212/0361151.html

    Why is Novocell the one getting the press? This is just baffling.

  3. gina
    gina February 27, 2008 at 8:52 am | | Reply

    We are having Dr. Cherie Stabler from the Diabetes research institute chat on March 19 so if anyone has questions they can ask her!

  4. Katie
    Katie February 27, 2008 at 8:53 am | | Reply

    I will never be able to understand why stem cell transplants get all the press– isn’t it true that no one has been able to rid T1′s of the autoimmune tendency that kills islets, regardless of whether the islets are from your own body, from stem cells, from human donors, etc.? Only Dr. Denise Faustman has made some progress with turning off this autoimmune attack, but only with mice. Why do stem cells get all the attention? Because no one wants to think about the fact that the immune system will destroy those new cells at some point and the “cured” person will have T1 all over again? I don’t get it.

  5. Merrill
    Merrill February 27, 2008 at 7:50 pm | | Reply

    So now in another article I see a drug cocktail when mixed with an anti-inflammatory enzyme will actually kick start the pancreas again into working. After time, enough islet cells will produce insulin in sufficient quantities again. Sounds like the magic bullet indeed.

    My question posed to my email to novacell was this. Scientists are now able to produce embryo like stem cells coaxed from skin cells. If the patients own skin cells were used to produce embryonic stem cells and then those cells are used to produce islet beta cells, would there be an autoimmune problem? As I see it there are two immunity problems, the first is the autoimmune problem caused by certain enzymes in the pancreas that cause the white blood cells to attack the islet cells. Apparently as the direct result of a particular gene in the patients body. The other is the immunity one has to cells introduced from other sources such as cadavers or pigs. My question was in regards to the outside sources and the body’s response to this. I’m uncertain about the ability to hide the new islet cells with the use of seaweed or algae and still have them function properly. While algae sounds good, has it actually been proven in tests? If not, has novacell even looked at this potential option of using skin cells as a direct source. Additionally, if lab generated islet cells from skin cells in sufficient quantity can be produced, they could possibly take the place of the current external sources and thus decreasing or leaving out entirely the use of anti rejection medicine. I do like to see scientists attacking the issue from all directions. Its getting close don’t you think? Tell me what you think.

  6. MoHo
    MoHo February 27, 2008 at 8:24 pm | | Reply

    I’m with Rob here, what about Microislet (in San Diego, CA) and LCT?! From what I have read they have been very successful with treating humans in Russia and NZ, specifically LCT. Microislets’ founder is a T1, too.

  7. Doug
    Doug February 28, 2008 at 10:02 pm | | Reply

    Hi Katie. You had a question as to whether scientists have proven that the alginate capsule protects the pig islet cells inside from the T1 patients immune system. Apparently the capsule is porous allowing the free exchange of glucose, insulin and all essential nutrients between the host and cells. However, the pores in the alginate capsules are small enough to exclude cells, keeping the pig islet cells in and the host immune cells out. Therefore, the islet cells are effectively hidden and the patient doesn’t need to have immunosuppresive drugs. They have injected these into patients in Russia and there have been no adverse events after nearly 9 months (immunoreactions etc).
    Apparently a clinical trial is planned for the Barbara Davis Centre for Childhood Diabetes in Denver, CO, starting 2009. In the press release i just read dated Feb 27, Prof Eisenbarth from the Barbara Davis Centre is quoted as saying “The lack of adverse effects and the encouraging early clinical results from LCTs first Diabacell(R) trial have prompted us to do a trial here in Denver.” Sounds like he has reasonable confidence that the alginate capsules work.

  8. Merrill
    Merrill March 1, 2008 at 9:48 am | | Reply

    Thanks Doug,

    That is so very exciting. Do you know of a way to become involved in the Denver tests? We live about 5 hours away in SE Idaho.

    Merrill

  9. MoHo
    MoHo March 1, 2008 at 9:24 pm | | Reply

    I wonder if the coated pig islets have a recurrent “low” problem like the stem cells. Amy, can you get the scoop? Please…

  10. Remi
    Remi July 19, 2008 at 12:32 am | | Reply

    The cells were then injected into a mouse model of muscular dystrophy. The injected cells contributed up to 94% of muscle fibers, providing therapeutic value by restoring muscle structure and function in the mice. The added adult stem cells also formed a reservoir of new satellite cells (repair stem cells) in the muscle, and could participate in further repair if there was subsequent injury to the muscle.

  11. LUIS
    LUIS September 2, 2008 at 6:28 pm | | Reply

    We have being trying with humans in Mexico (Juarez Chihuahua)8 months ago ,we have implanted 190 cells in 190 patients , 57 of them are diabetics [54 type 2 and 3 type 1] but the cells we use are from their own body they are called Adult stem cells.Obtained from the pacient bone marrow with out any possible side efect , so far the results have being good on 80% of the patients and the other 20% have responded slowly.

    One big problem is the follow up of the treatment ,because the tretament requires at least 3 months to see results plus the following therapy .

    We are doing know also the harvest of the stem cells that way the patients can see results sooner . Like I said before we barely started 8 months ago and so far it’s been good . We are getting more patients that have diabetes type 2 every month , I will keep you all posted with the results.

    Thank you Luis M.

  12. Diabetes research news - Diabetes Daily Voices

    [...] Tenderich has posted on her blog about Novocell and their success in using human stem cells to generate insulin in mice. [...]

Leave a Reply