TAU's Insulin-cell Discovery Offers New Hope for Diabetics

Investigators at Tel Aviv University have announced the discovery of a new way to generate human insulin-producing cells in tissue culture, which will provide an abundant source of cells for transplanting to juvenile diabetes sufferers.

The findings of Prof. Shimon Efrat of TAU and his American collaborators are reported this week in the Proceedings of the National Academy of Sciences. It says if ways can be found to prevent the cells from being rejected by the immune system, they can be used in humans within a few years.

The team used stem cells from human fetal liver, which can be easily propagated in tissue culture, and modified the cells by introducing a gene responsible for the embryonic development of insulin-producing cells.

The engineered cells produce about a third of the insulin made by insulin-producing cells in the pancreas. When transplanted into diabetic mice, the cells were able to reduce the elevated blood sugar levels and maintain a normal level for a period of several months.

Some 5 percent of the world suffers from diabetes, making it a major public health concern. Complications from diabetes include heart disease, strokes, kidney failure, blindness, and limb amputation. Type 1, juvenile diabetes, which is responsible for 10 percent of the cases, is caused by an auto-immune destruction of insulin-producing beta cells.

Type 2, adult onset diabetes, representing some 90 percent of the cases, afflicts mostly people aged 45 and older. It results from the body's inability to respond to insulin, and is associated with obesity and a sedentary lifestyle, which explain its increased incidence in modern society.

In the U.S. treating diabetes costs about $100 billion a year, with the main treatment being insulin injections. But as the disease progresses, many patients need ever increasing amounts of the hormone, and the injection becomes less effective. The discovery of a more effective treatment cold significantly improve the quality of life of the patients - and bring riches to the developers of the new treatment.

Treatment of type 1 diabetes by insulin administration cannot avoid long-term complications, due to the difficulty to determine the exact insulin dosage required in changing physiological conditions. The optimal treatment for type 1 diabetes is likely to be the replacement of the damaged beta cells with intact beta cells through transplantation, such as those developed in the latest research.

This therapy may also eventually be applicable to type 2 diabetes. In its early stages this form of the disease is managed through a combination of drugs that increase insulin secretion, and lifestyle changes in diet and exercise. However, 40 percent of type 2 diabetes patients eventually require injections of large doses of insulin.

Pancreas and islet transplantation have been severely limited by the shortage of donors and by the destruction of transplanted beta cells due to recurring autoimmunity. The laboratory of Prof. Shimon Efrat focuses on the development of new sources of beta cells for transplantation and on ways to protect them from immune attacks.

Beta cells do not multiply in tissue culture. In recent years investigators have attempted to generate beta cells from stem cells. Embryonic stem cells, derived from embryos a few days old, can replicate well in tissue culture and were shown to give rise to a variety of cell types. Fetal and embryonic tissues contain tissue stem cells, which are responsible for tissue maintenance throughout life. They too were recently shown to be capable of developing into other cell types. Prof. Efrat is using genes known to play a role in pancreas development, as well as various inductive tissue culture conditions, to instruct stem cells to develop into insulin-producing cells in tissue culture.

The cells described in the new publication may be used for transplantation if a way can be fond to protect them from immune destruction. This will open the way for cell therapy of type 1 diabetes that will not depend on scarce tissue donations.