Embryonic Stem Cell-Derived Beta Cells Cure Diabetic Mice

Stem cell scientists in Canada have collaborated with biotechnology industries to successfully reverse diabetes mellitus in mice by means of stem cell treatments. This is certainly a medical breakthrough that might lead to treatments in human patients.

The lead researcher, Timothy Kieffer, who is a professor at the University of British Columbia, and scientist from the New Jersey-based company BetaLogics showed that stem cell transplants can restore insulin production and reverse diabetes mellitus in mice.

Beta cells reside in an organ called the pancreas, which is behind the stomach. The pancreas has an “exocrine” function, which means that it secretes materials such as digestive enzymes and bicarbonate ions into a duct, and an endocrine function, which means that it secretes hormones directly into the bloodstream. The exocrine function of the pancreas is accomplished by clusters of cells known as “acinar cells.” Acinar cells cluster around a tiny branch of the pancreatic duct, and they secrete digestive enzymes and bicarbonate ions into the pancreatic duct, which are released into the upper portion of the small intestine (duodenum). These enzymes degrade fats, proteins, nucleic acids, and carbohydrates in the small intestine, which prepares the complex molecules in food for digestion. The endocrine functions are carried out by islands of cells dispersed throughout the pancreas that are away from the pancreatic duct, but clustered around blood vessels. These “pancreatic islets” as they are called secrete hormones that regulate the metabolism of food-derived molecules in our bodies.

There are five types of cells in pancreatic islets: alpha cells, beta cells, delta cells, epsilon cells and PP cells. Alpha cells secrete a hormone called glucagon, which mobilizes store sugar stores in the body and releases them into the bloodstream, this raising blood sugar levels. Beta cells secrete insulin, which stimulates the uptake and metabolism of bloodstream sugar, thus lowering blood sugar levels. Delta cells secrete somatostatin, which regulates growth hormone release by the anterior pituitary, but also affects the release of many hormones in the digestive system and inhibits the release of glucagon and insulin. The epsilon cells secrete a hormone called ghrelin, which is a potent appetite stimulant. The PP cells secrete PP or pancreatic peptide, which helps the pancreas to self-regulate its secretory activities, both exocrine and endocrine.

Once glucose levels rise in the blood, the beta cells release insulin, and when glucose levels in the blood decrease, insulin secretion decreases. This “feedback loop” is essential for proper regulation of blood glucose levels, and beta cells that are immature do not properly respond to rises in blood glucose levels. In this study, however, the research effort completely recreated the insulin/sugar feedback loop that enables insulin levels to automatically rise or fall according to the blood glucose levels.

Damage to the beta cells results in insufficient insulin production and poor regulation of the blood sugar levels. Damage to the beta cells results in type 1 diabetes mellitus, and without the secretion of sufficient quantities in insulin after a meal, the cells do not receive the signal to take up sugar, and are starved from energy. Meanwhile, extremely high sugar levels in the blood react with molecules in the organs of the body, which causes long-term damage to the nervous system, eyes, kidneys, and peripheral tissues. Consequently, type 1 diabetics are at increased risk for amputations, blindness, heart attack, stroke, nerve damage and kidney failure.

Regular injections of insulin are the most common treatment for type 1 diabetes mellitus, but experimental transplants of healthy pancreatic cells from human donors have shown to be effective. Unfortunately, such a treatment is severely limited by the availability of donors.

In this experiment, human embryonic stem cells were differentiated into beta cells and implanted into the diabetic mice. After the stem cell transplant, the diabetic mice were weaned off insulin. Three to four months later, the mice were able to maintain healthy blood sugar levels even after being fed large quantities of sugar. Transplanted cells removed from the mice after several months had all the markings of normal insulin-producing pancreatic cells.

These experiments, however, have one very large caveat. In the words of Kiefer: “We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans. The studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells. We now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression.”

Type 1 diabetes usually results from the immune system of the diabetic patient attacking their own beta cells. Replacing the beta cells mere gives the immune system something that it already recognizes to attack. Therefore, replacing the beta cells with new beta cells from any other source is potentially problematic.

There is a possibility that the beta cells could be implanted inside a porous encasement that is not accessible to the immune system, but can still secrete insulin into the bloodstream in response to increase blood sugar levels. Such a strategy would circumvent the immune system problems.