Stem Cells and Diabetes

*I would like to start with a disclaimer. My laptop is broken (AGAIN), and until I invest in a new harddrive, I am going to have to write all the posts on this little netbook, Ruby, who, while intrepid, can't do JACK when it comes to images. Which means I'll have to add the images in the AM. My apologies.

Sci found this paper today and immediately had to run around showing it to people and saying "OMG isn't this COOL!!" At first, it was so cool that I thought I should save it for a special occasion, but dangit, I'm feeling celebratory. Anyway, I wanted to blog it NOW.

And since this is Sci's blog, what Sci wants, Sci gets.

And I love this paper. Alipio, et al. "Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic β-like cells" PNAS, 2010.

So first, let's talk a little about diabetes.

Sci has posted a bit about diabetes previously, but I'll recap here a little bit.

Basically, diabetes is a disorder where your body lacks insulin, which you probably already know. Insulin, which is a protein produced from the beta cells in the pancreas, is a molecule which allows your cells to take up glucose. Glucose, as you know, is a potent form of energy that we get from food, and your body is very hard put to survive without it. So you really need insulin to get your glucose into your cells, or your cells will literally begin to starve to death.

And now we get to diabetes:

Type I

What happens in Type I diabetes is that your body destroys and rejects the beta-cells which make your insulin in the pancreas. Without beta cells you produce no insulin, and so the only cure at the moment is to supplement insulin in diabetic patients on a daily basis. While Type I diabetes only affects about 3.5 percent of the total population, giving insulin in not a cure, and it has significant impacts on quality of life, as well as having a lot of side effects associated with it which can shorten the lifespan.

Type II

Some scientists are starting to think of type II diabetes as a precursor to type I, as many patients with type II will go on to develop type I and become insulin dependent. Type II diabetes is not an inability to make insulin, instead, it is either a condition of not making enough, or not being sensitive enough to what you DO make. Sometimes this can be managed with lifestyle (when some people gain too much weight they become insensitive to insulin) or with some drugs, but many patients with Type II diabetes will also end up having to dose with insulin. This type of diabetes is much more widespread, affecting up to 7% of the population.

So now we get to the issue of this paper, the issue of the beta cells.

Type I diabetes, as I mentioned up there, occurs because of the destruction of the beta cells which produce insulin. So the idea is, if you could get the body to REMAKE the beta cells, you could cure diabetes. Sounds simple right? Well, not really. Previous ideas to get this effect have been tried with pancreas transplants or trying to get beta cells reintroduced, but often the body will reject the donation. Other methods tried using beta cells that have been induced from bone marrow cells, but the cells coming from there don't differentiate into beta cells very well, and don't really produce a lot of insulin.

But what about pluripotent stem cells?

An induced pluripotent stem cell (called an iPS) is a stem cell (a cell that can become lots of different things) that is deliberately induced from an already-differentiated adult cell. You can do this by reprogramming the cells using viruses to transfer the DNA that you need. They are very similar to the embryonic stem cells of controversial fame, but are derived from adult cells that are already in your body. This is a good thing, because if it's a part of your body, you can't reject it.

In this case, the scientists took mice, and made two models of diabetes. The first one is a type II diabetes model, which shows low levels of insulin production. The second was a mouse given streptozotocin, which is a chemical that kills beta cells in the pancreas, giving the mouse type I diabetes.

They took skin cells from mice and made them into iPS cells using viruses. The cells were also labeled with GFP, so they knew what they were looking at by the glow. After treatment with the viruses, the former skin cells differentiated into muscle and gut and all sorts of other things. They then differentiated them into beta cells, and checked to see how they did with glucose.


You can see above the beta cells exposed to glucose. And they behaved just like beta cells should, pumping out insulin in response to the glucose.

But the question is, would it work in the mice? They injected the new beta cells into the livers of the diabetic mice and looked.


And it did. You can see up there four lines. The two top lines are the fasting glucose levels of untreated type 2 diabetic mice and mice treated with a fake injection of cells. The two bottom lines are a mouse with no diabetes and a mouse treated with the stem cells. You can see the stem cell treated mice look just like a normal mouse. What's happening here is that in the diabetic mice, there is no insulin to make the glucose in the blood go into the tissues, and so their blood glucose levels are HIGH. In the normal mice (and the stem cell treated mice) there is enough insulin being produced to get glucose from the blood to the tissues, and so glucose levels are LOW!


And here you can see mice that have type I diabetes, who have no beta cells at all. The top line are the controls, and the bottom line is the diabetic mice treated with iPS cells. You can see that the treated mice had a dramatic decrease in blood glucose, showing that the stem cells they received became beta cells and were pumping out insulin like they should.

While the treatment didn't work in all of the mice (two of the type 2 diabetic mice had high blood sugar levels soon after), this paper could be GREAT news to people with type I and type II diabetes. If we can induce human cells to produce iPS cells, we could put them back into the humans and potentially reduce their blood sugar levels. Not only that, the stem cells also produced alpha cells in addition to beta cells. Alpha cells produce glucagon, which is a very important part of the insulin response, and type I diabetes destroys both alpha and beta cells. So having them both back would be even better than having just one, as the two types could work in concert.

However, you have to keep in mind that we aren't there yet. This was in mice, and iPS cells aren't as well characterized in humans. Not only that, a lot of type I diabetes and later stages of type II diabetes has an IMMUNE COMPONENT. This means that the body will continue to try and make beta cells, and it will also reject and destroy them, even though they are normal cells and not an invasion. So it's possible that these cells could still be rejected.

But despite the caveats, this is a big step in the right direction, and it gives Sci hope that a cure for diabetes may come sooner rather than later.

Alipio Z, Liao W, Roemer EJ, Waner M, Fink LM, Ward DC, & Ma Y (2010). Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic {beta}-like cells. Proceedings of the National Academy of Sciences of the United States of America PMID: 20616080

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