Islet Cell Transplant Update

Q: What information do you have on the latest work being done on islet cell transplants for type I diabetics? When my 13-year-old daughter was diagnosed four and a half years ago, it seemed a cure was around the corner. Now it seems there are more obstacles than resolutions. Any hopeful information?

A: The hope cannot be expressed with a promised date, or even with a promised “breakthrough.” But, we can now identify with confidence the problems that must be overcome and better understood.

The world leaders in this field met at the International Pancreas and Islet Transplant Association conference in Milan in late September. The general feeling of the conference participants is that little progress has been made in the past few years.

Transplantation of islets into diabetic kidney transplant recipients is an established procedure that is now regarded as safe. It is often effective in reducing or eliminating a diabetic’s dependence on injected insulin. And the improved blood sugars are indeed associated with reduced vascular complications.

However, this procedure can never become routine for the mass of diabetics because only a few will ever have kidney transplants. Thus, a technology is needed that allows islets to function in the absence of the immune suppression drugs given during kidney transplantation. The requirements for such a technology are becoming clearer.

The most difficult requirement has turned out to be biocompatibility. There is great confusion about the term “biocompatibility” because device and transplantation people use the same term to mean different things. For a device, biocompatibility means that the material induces engraftment; the vascular graft is covered with a layer of collagen fibers permitting overgrowth of endothelial cells (flat cells that line the blood vessels). But such overgrowth will starve a cellular implant! For a cellular transplant, biocompatibility means lacking collagen fibers or any material that will promote cellular adhesion.

The difference is shown in the figure on page one. The body’s reaction to material appropriate for a vascular implant (and inappropriate for a bioartificial pancreas) is shown in the upper path; reaction to material appropriate for a bioartificial pancreas is shown in the lower path.

In both cases the initial interaction is between the material and immune system cells and fibroblasts (purple). For the vast majority of materials, the cells react to foreign bodies by laying down collagen fibers (green). The collagen fibers are then populated by endothelial cells (brown).

A bioartificial pancreas made of the material in the upper path would starve the cells inside because the collagen and endothelial cells prevent nutrients from reaching the cells inside.

The other great problem to be overcome is diffusion of oxygen. Islets must have oxygen to survive. If the device is too thick, it is impossible for enough oxygen to diffuse in and the islets cells die as a result. For example, the capsules used to cover islets in a well publicized human study a few years ago are too large, and the islets inside are known to die.

Some researchers are working on designs using materials that may overcome these problems. With the well-known history of unfulfilled promises, I will not predict how much longer it will take!

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