Living pancreatic islet cell donation

A fascinating article and associated commentary posted today at Lancet (only for subscribers but see press account here). A Japanese woman with severe, brittle type I (insulin dependent) diabetes was treated by transplantation of pancreatic isletes (which contain the insulin producing beta-cells) harvested from her mother.

For non-experts, Type 1 diabetes (sometimes called insulin dependent) is due to inability to produce insulin, usually because the body's immune system has destroyed most or all of the beta cells in the pancreas whose job is insulin production. There are a few other rare causes, like recurrent pancreatitis (basicially, inflammation of the pancreas) that can cause it as well, as in this case (which is important as we'll see in a minute). Patients with Type 1 diabetes tend to be young and thin.

Type 2 diabetes is because of inability to produce enough insulin. It often happens in older, often obese patients. Some of these patients require insulin, but they can still make some insulin themselves. The insulin also doesn't seem to work as well as in other people, so it is said they are insulin resistant.

Treatment of Type 1 diabetes involves frequent measurements of blood sugars and injections of insulin several times per day. Even then patients are prone to complications from chronically elevated blood sugars such as kidney and heart problems, loss of vision and poor wound healing. Overagressive use of insulin can lead to episodes of hypoglycemia (low blood sugar) which can be fatal. Obviously better treatments are needed. Insulin pumps which are planted in the body can help some, but have some problems of their own.

The holy grail of Type I diabetes would be to give patients back pancreatic beta cells and therfore the ability to produce insulin. Beta cells have a complex sensing mechanism which integrates information such as blood sugar level, nutritional status etc and secretes just enough insulin. That is why most of us (w/o diabetes) never think twice about our blood sugar. Even checking blood sugar 4x/day and guessing about what one is going to eat is nowhere near as good as the beta-cell at optimizing insulin secretion. Not even close

Various methods of restoring beta-cell function have been tried including transplant of a pancreas from an organ donor (or part of a pancreas from a living donor) and infusing the insulin producing islet cells back into the body. More speculative at this point are using stem cells to grow new islet cells and put them back in.

One problem with these strategies is that the recipients immune system can destroy the new beta-cells as efficiently and ruthlessly as it did the original ones. In addition, with transplant of islets or the (islet containing) pancreas itself the immune system will recognize the tranplanted tissue as foreign and attack it. Therefore with all of these strategies, patients need to remain on powerful immune suppressive mechanisms with many side effects.

A group in Edmonton has recently had good success isolation islet cells (which include beta-cells) from cadavers and reinfusing them into the portal vein. The islets then lodge in the liver and start to function, excreting insulin when the blood sugar gets high. The results and their importance is controversial (not in a bad way). Multiple pancreases from different donors are required because the yield of islet cells is low, making widespread use impractical, at least for now. Because islets are harvested from dead people, a lot of them die before they can be harvested. In addition, processing to isolate the islet cells and keep the volume of cells lows leads to further loss of cells. Patients have become insulin independent (although now immune suppressive dependent) and how long the new islet cells will survive is unclear.

Now a Japanese group has reported successful islet transplantation using a living donor. The patient had difficult to control diabetes for a number of years from chronic pancreatitis. Her mother served as donor and had about 1/2 her pancreas removed. The donated pancrease was broken down into small chunks using enzymes, but because the volume was already low, complicated purification of islets was avoided. The patient did well after tranplantation and became insulin independent pretty quickly.

I think this is very cool, but am not sure how useful it will be.

Remember this patient did NOT have autoimmune destruction of islets, so survival of transplanted islets in her may be better than in typical type 1 diabetes patients. Also, it is unclear what the risk to the donor is. Earlier reports have shown increased risk of diabetes in pancreas donors, so only non-obese patients with no evidence of glucose intolerance (basically pre-diabetes type 2) and no evidence of islet cell immunity are considered potential donors (the donor in this case met all these criteria).

Eventually, I think stem cells will be the source of islet cells, hopefully stem cells derived from the patient themselves, but that is a ways off. For now, I think this is a big advance, but the whole field is really awaiting safer immunosuppressive drugs (or alternative methods of preventing immune destruction of transplanted beta-cells) so both cadaveric and live donation of islets can be used more widely. As the authors of the assoicated commentary note:

Recent publicity about the UK’s nascent programme of islet transplantation resulted in a stream of inquiries from parents and grandparents of children with
diabetes, desperate to offer their children relief from the urgent needs of living with insulin-deficient diabetes.

I know if my child had diabetes, I'd be happy to give part of my pancreas to cure them.