Insulin cell transplant gives hope to diabetics

Related tags Immune system Insulin Diabetes mellitus

Living Cell Technologies (LCT) are set to put a major dent in the
market for diabetic treatments after they announced the retrieval
of live, insulin-producing cells, from a patient, in a transplant
that did not require the use of immunosuppressive drugs.

The transplant, in which the cells were retrieved after nine years, has startled the scientific community and could potentially provide a near-term solution for type 1 diabetes sufferers, which are expected to reach 24 million within 5 years.

In addition, the absence of immunosuppressive drugs to prevent rejection could make the devastating side effects associated with this therapy a thing of the past. The most popular group of immunosuppressive drugs, whilst effective, also leave an individual hopelessly susceptible to infection.

In potentially pioneering research, a 40-year-old man with Type 1 diabetes received a transplant of an early prototype of LCT's DiaBCell in 1996, as part of a clinical trial. Type 1 diabetics are not able to produce sufficient insulin of their own.

The pig islet transplants were intended to release insulin and restore control of blood glucose levels. The pig islets were encapsulated with a seaweed-derived coating alginate capsule to protect them from immune rejection and no immune suppressive drugs were needed for this transplant.

Paris Brooke, general manager of Living Cell Technologies told​: "The cells are coated with a proprietary formulation of a naturally occurring gel called alginate. Used for many decades as a food additive or surgical implant, alginate comes from seaweed and is what protects the cells of the seaweed from the harsh aquatic environment."

The final produce is comprised of the cells encapsulated in transparent microspheres the size of small grains of sand (approx. 400 microns) loaded into disease specific packaging. Made from alginate gel, the coating shows effective pore size is controlled with a passivating protein coating. The capsules enable long-term cell survival and function by protecting them form the recipient's immune system.

"The ability to control the effective pore size dictates the capsules permselectivity (what molecules are allowed to pass through the wall). This proprietary encapsulation technology enables the company to effectively transplant replacement cells, without the use of crippling immunosuppressive drugs,"​ he added.

"The alginate capsules act as a permeable barrier, that enables nutrients and factors to flow in and out of the cells/capsules, but the pore size does not allow antibodies and immune cells to enter the capsule or affect the living transplanted cells function,"​ said Brooke.

"The effective pore size is controlled with a passivating protein coating, the capsules enable long-term cell survival and function by protecting them from the recipient's immune system,"​ he added.

The research found that for about one year, the patient's insulin dosage was reduced by as much as 34 per cent and control of his diabetes improved. However, by two years the daily insulin requirement returned to the pre-transplant dose.

"The patient insisted that the site of the transplant (the abdominal cavity) be examined. We were pleasantly surprised to see a small number of intact capsules. The capsules contained live pig cells,"​ said Professor Bob Elliott, LCT medical director.

"A few were removed and produced a detectable amount of insulin in culture when stimulated with glucose. Analysis using microscopy further indicated that these few cells contained insulin,"​ he concluded.

Although the discovery was for one patient, the result has demonstrated that it is feasible that pig cells within capsules, when placed in the abdomen, can be protected for a long period of time and, continue to produce small amounts of insulin.

Current treatments for insulin dependent diabetes treat the symptoms and not the disease. Insulin injections are not capable of responding to varying blood sugar levels and these poorly controlled levels result in secondary problems.

Pig islet transplantation is of particular interest to medical practitioners and patients since implanted islets can replace the insulin-producing function of the pancreas, which is lost in individuals with type 1 diabetes. The extremely limited availability of suitable human islets for transplantation makes the therapeutic use of pig islets an important alternative, particularly because pig insulin is almost identical to human insulin and has been used clinically since the early part of last century.

LCT​ is currently focusing on two product lines in type 1 diabetes and huntington's disease. Brooke said that the well-characterised primary cells meant that the company is not dependant upon early stage, long-term research. Both the type 1 diabetes and huntington's products (DiabeCell and NeurotrophinCell) have finished pre-clinical trials, with the aim of obtaining US FDA regulatory approval to enter phase 1 clinical trials in 2006.

"A lot of research and development have gone into optimising viable age of the porcine cells, alginate parameters, timing of encapsulation etc. Considerations for the future will be the sufficient production of cells to meet market demand,"​ he said.

Related topics Preclinical Research

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