Diabetes exacts its toll on many Americans, young and old. For years, researchers have painstakingly dissected this complicated disease caused by the destruction of insulin producing islet cells of the pancreas. Despite progress in understanding the underlying disease mechanisms for diabetes, there is still a paucity of effective therapies. For years investigators have been making slow, but steady, progress on experimental strategies for pancreatic transplantation and islet cell replacement. Now, researchers have turned their attention to adult stem cells that appear to be precursors to islet cells and embryonic stem cells that produce insulin.
Diabetes is actually a group of diseases characterized by abnormally high levels of the sugar glucose in the bloodstream. This excess glucose is responsible for most of the complications of diabetes, which include blindness, kidney failure, heart disease, stroke, neuropathy, and amputations. Type 1 diabetes, also known as juvenile-onset diabetes, typically affects children and young adults. Diabetes develops when the body’s immune system sees its own cells as foreign and attacks and destroys them. Type 1 diabetes accounts for 5 10% of diabetes cases. Type 2 diabetes, also called adult-onset diabetes, tends to affect older, sedentary, and overweight individuals with a family history of diabetes. Type 2 diabetes occurs when the body cannot use insulin effectively. This is called insulin resistance and the result is the same as with type 1 diabetes a build up of glucose in the blood.
pancreatic transplantation and islet cell replacement
There is currently no cure for diabetes. People with type 1 diabetes must take insulin several times a day. People with type 2 diabetes can often control their blood glucose concentrations through a combination of diet, exercise, and oral medication. The demand for transplantable pancreases outweighs their availability. To prevent the body from rejecting the transplanted pancreas, patients who receive whole-organ pancreas transplants must take powerful drugs that suppress the immune system for their entire lives, a regimen that makes them susceptible to a host of other diseases. The deleterious effect of steroids immunosuppressant therapy is greater for pancreatic islet cell transplants than for whole-organ transplants. More recently, James Shapiro and his colleagues in Edmonton, Alberta, Canada, have developed an experimental protocol (widely-known “Edmonton protocol”) for transplanting islet cells that involves using a much larger amount of islet cells and a different type of immunosuppressant therapy. If the success of the Edmonton protocol can be duplicated, many hurdles still remain in using this approach on a wide scale to treat diabetes. First, donor tissue is not readily available. Islet cells used in transplants are obtained from cadavers, and the procedure requires at least two cadavers per transplant. The islet cells must be immunologically compatible, and the tissue must be freshly obtained within eight hours of death. Further, islet cell transplant recipients face a lifetime of immunosuppressant therapy, which makes them susceptible to other serious infections and diseases. While these strategies continue to be improved, islet function declines relatively rapidly post-transplant.
Many researchers have focused on culturing islet cells from human adult cadavers for use in developing transplantable material. Although differentiated beta cells are difficult to proliferate and culture, some researchers have had success in engineering such cells to do this.
pancreatic stem cell and (stem) cell-based therapy
Many researchers maintain that some sort of islet stem cell can be found intermingled with ductal cells during fetal development and that these stem cells give rise to new endocrine cells as the fetus develops. Following birth and into adulthood, the source of new islet cells is not clear, and some controversy exists over whether adult stem cells exist in the pancreas. Some researchers believe that islet stem cell-like cells can be found in the pancreatic ducts and even in the islets themselves. In addition, several new promising studies indicate that insulin-producing cells can be cultivated from embryonic stem cell lines. Many researchers believe that it will be preferable to develop a system in which stem or precursor cell types can be cultured to produce all the cell types of the islet cluster in order to generate a population of cells that will be able to coordinate the release of the appropriate amount of insulin to the physiologically relevant concentrations of glucose in the blood.
Several groups of researchers are investigating the use of fetal tissue as a potential source of islet progenitor cells.
Another promising source of islet progenitor cells lies in the cells that line the pancreatic ducts. Some researchers believe that multipotent stem cells are intermingled with mature, differentiated duct cells, while others believe that the duct cells themselves can undergo a differentiation, or a reversal to a less mature type of cell, which can then differentiate into an insulin-producing islet cell.
In theory, embryonic stem cells could be cultivated and coaxed into developing into the insulin-producing islet cells of the pancreas. There is also some evidence that differentiated cells derived from embryonic stem cells might be less likely to cause immune rejection. Recent research has also provided more evidence that human embryonic cells can develop into cells that can and do produce insulin.
