New cell transplant for diabetes

21 January 2020

Interview with 

Professor Shareen Forbes, Edinburgh University

DIABETES

DIABETES, TYPE 1 DIABETES

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Diabetes - and a better way to manage the condition in some people. Diabetes comes in two forms; type 2 diabetes is usually associated with being overweight and it’s more common in older people. Type 1 diabetes, on the other hand, often begins in childhood and is caused by the immune system attacking the islet cells in the pancreas, meaning that patients can’t make any of the insulin they need to control blood glucose; instead they have to inject it. But despite this, for some people the condition can become extremely difficult to control. When this happens, doctors sometimes resort to a procedure called an “islet cell transplant” to replace the lost insulin-producing cells with donor cells. While this can control blood sugar, the downside is that patients need to take immune-suppressing drugs, and the benefits may only be short lived. Now, researchers in Edinburgh have discovered a way to boost the effectiveness of the transplanted cells: by adding alongside them stem cells collected from the umbilical cords of newborn babies. Chris Smith spoke to Shareen Forbes…

Shareen - So in an islet transplant, a pancreas is donated, the insulin producing cells are isolated, they're purified, and the vein to the liver is actually identified and the islets are actually infused. Just fire a needle into this vein!

Chris- And those cells presumably drift along and then lodge in the liver where they do the job they would do in the pancreas but they're doing it from within the liver?

Shareen - That's right. But there are major issues in that the islets go in without a blood vessel supply. Then blood vessels form within the first 48 hours to seven days. So they're very vulnerable to dying off in that period.

Chris- And when you do one of these transplants, how long does the effect or the benefit last for?

Shareen - That can be very variable. In many patients the graft function can deteriorate and it may last maybe 10 years.

Chris- And you have got a way of improving the prognosis, have you?

Shareen - We're hopeful that our experiments might lead to further experiments, in man, where we're hopeful that this might actually have improved effects. My colleagues at the Scottish National Blood Transfusion Service characterised and made something called stromal cells from umbilical cord. So this is umbilical cord that would normally be thrown away and these cells they found produced growth factors and also affect the immune system. And what we found when we co-transplanted these cells with the islets, blood glucose levels were improved for a longer period of time and the rejection of the insulin secreting cells was less, as compared to our parallel experiments where just islets alone were transfused into the mouse models.

Chris - So you did this in mice. Where did you put the insulin secreting cells, the islet cells, with these new umbilical cord derived cells? Where did you put them?

Shareen - So we put them both under the kidney capsule, which is an experimental route, which allows us to assess the vascularisation well, so the amount of blood vessel formation well. And with that route we showed that the amount of blood vessel formed was much greater in the mixture of the cells with the islets as compared to the islets alone. And we also transplanted them into the liver, so we emulated the clinical scenario in man and showed again that the effects on blood glucose control was much improved.

Chris - Do you think this is just attributable to the blood vessels behaving better when you've got these umbilical cord cells there or do you think that the umbilical cord cells are manipulating the immune response as well?

Shareen - I think that it's both factors which are important. The cells have a lot of anti-inflammatory properties and they also can modulate the immune response. So I think there's a protective effect there, as well as what you've mentioned, enabling the formation of blood vessels to form much more quickly and therefore protect the insulin producing cells.

Chris - And if you do a comparison of a mouse that doesn't get these new cells but does get the islet transplant and a mouse that gets the same islet transplant, but with some of these new cells, how much better off is the second situation?

Shareen - We show in our study that actually blood glucose levels are mainly cured. Mice that received the islets alone, their blood glucose levels would double versus, those that received the same number of islets plus these cells.

Chris - So do you think this is a realistic clinical prospect now, to take what we know works in these mice and translate that to people? Because we are using umbilical cord blood STEM cells in the clinic at the moment for other things, aren't we? So presumably there's already a tried and tested route for using these sorts of cells so it's not such a leap to now translate this?

Shareen - We need to go into larger animal models and then do safety studies before we go into man. But certainly it's a realistic step change in the field.

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