Diabetes stem cell trial offers hope of cure

Interview with James Shapiro, University of Alberta

Part of the show Diabetes cured with stem cells, and US bans Chinese tech

A woman with type 1 diabetes has started producing her own insulin three months after receiving a transplant of reprogrammed stem cells. The findings - which have been published in the journal Cell and are based on work done by a team in China - give us hope that type 1 diabetes can be reversed. James Shapiro, a transplant surgeon and researcher at the University of Alberta in Edmonton, Canada, where he’s been working on similar ways to manage diabetes, says the results are “stunning”. We asked him to take a look at the study for us…

James - This group in Tianjin took a patient with type 1 diabetes and they took some stem cells from the fat and they turned those stem cells into insulin producing cells, and they transplanted those cells that make insulin back into the muscle layers in the tummy wall. And after a period of time, it took about three months, the 25-year-old lady was able to come off insulin entirely because the cells were fully functioning.

Chris - How did they persuade fat cells to become insulin producing cells?

James - Well, it's a complex process and they describe it in great detail, of course, in their paper. But they've been testing this idea since 2021, making cells from a patient's fat. And then they basically coax the cells into what are called malleable cells. They've got a fancy name IPS cells or stem cells. And then once they've made these stem cells, they can then wind them forward in time pretending that they're inside the body, inside the pancreas in fact. And by adding different chemical growth factors at different time points, they can coax the cells out into being insulin producing cells.

Chris - Why did they start with fat?

James - Well, I don't know the answer to that. It's a very good question and it's very original. So in our own lab we've been working on blood and there's another group in Shanghai that also did the same thing, taking the stem cells from the blood and then turning them into islet cells. But this group chose fat and it seemed to work very well in their hands.

Chris - How well did it work? So if you look at this lady's diabetic problem, how big of an issue was it for her and how much control did this restore for her? Did did it completely divorce her from the need to have insulin, for example, once they'd done this for her,

James - She had difficult to control diabetes before the procedure. After the procedure, after about three months, she had everything in the green. So a spectacular function of those cells, completely normal at blood glucose, blood sugar profile. Really remarkable.

Chris - How long have they tested her for?

James - She's been followed out for a year, and that's what this report shows. And they've apparently done two other patients who they have not reported on yet. And this sort of follows on the coattails of a different group. This is in Tianjin, just south of Beijing in China. And there's a second group in Shanghai that has done something very similar to this. But they put their cells inside the liver rather than in the muscle layer.

Chris - One of the things leaping out at me about this is if one asks, well why does a person become a type 1 diabetic in the first place? Usually it's because the immune system has wiped out their ability to produce insulin. They develop an autoimmune disease for various reasons. Why doesn't that happen with these new insulin producing cells then?

James - Well, that's a really great question and it might. But this particular patient was an unusual patient because she's had two liver transplant surgeries and she takes powerful anti-rejection drugs to stop the liver from being rejected. And I suspect in this situation, the same drugs that are preventing the liver from being rejected are stopping that autoimmune process. So it has not come back in her to date.

Chris - So in other words, if a person listening to this is type one diabetic and thinks, well this is great, I could just go through this, there may well be a higher price to pay than just turning your fat cells into some new insulin producing cells.

James - I don't know about a higher price to pay. But I think there will be some additional tricks or tweaks that will be needed to stop those cells from being destroyed by the autoimmune process again. And it might be a lot easier to do that than it would be to stop the standard rejection process. The beautiful thing about these cells is because they're the patient's own cells, they're not going to get rejected by the body because of that.

Chris - Can you foresee any other risks of doing this kind of thing?

James - Well, there are potential risks. Because these are stem cell made, it's possible that they could develop into unwanted cells or what we might call off target cells. So they could make cysts or they could make unwanted cell products. This hasn't happened in this case. They've done some very, very detailed and beautiful studies of the muscle layers and shown that they're quite normal, but there is a potential risk. So as this kind of work moves forward, I think we need to be very cautious and make sure that there are no off-target risks to children and adult adults in future that receive these cells.

Chris - But overall, your view is very positive of this.

James - I'm exceedingly excited by this. We've been transplanting islet cells into the liver in 470 patients in Edmonton over the last 25 years, putting cells into the liver. And we've seen some excellent outcomes. But those patients have to take powerful anti rejection drugs to stop the cells from being destroyed by the immune system. If this approach works and if it's safe, this really could be a new frontier for patients with all forms of diabetes. I'm very excited about it.