Cell-based options for diabetes treatment

From "Diabetes Management: Products, Technologies, Markets and Opportunities Worldwide 2009-2018", Report #D510.

 

At the forefront of those technologies seeking to reverse diabetes or at least target the underlying disease are the cell-based options to restore normoregulated blood glucose levels. These include pancreas transplants, islet cell transplants and a number of stem cell transplant options.

Pancreas Transplants

Pancreas transplantation has been widely practiced for some years and has been successful in a majority of patients. It is not appropriate for all diabetics as it is, for example, too invasive for children, and cost is a major deterrent. Also, immune rejection of the transplanted organ is a constant threat which must be counteracted by daily immunosuppressant drugs. Another major problem is the shortage of available organs for transplantation compared with the much larger demand.

Pancreas-alone transplants are performed when there is normal or near-normal kidney function. This option may be recommended for patients who have frequent insulin reactions or poor blood glucose control despite best efforts to manage the disease. Most transplant recipients are 55 years or younger, have type 1 diabetes and are healthy enough to undergo the procedure. About 95% of pancreas transplantation are performed in patients with renal disease or who had a previous functioning kidney transplant. In the United States, roughly 1,200 people receive pancreas transplantations each year. If insulin treatment and monitoring strategies are working, a transplant is unlikely to be a better option. According to pancreas transplantation results reported to the Scientific Registry of Transplant Recipients of the United Network for Organ Sharing and the International Pancreas Transplant Registry, survival rates for recipients of a simultaneous pancreas-kidney (SPK, i.e., from the same donor) transplant were 85%–95%. Compared to diabetic patients receiving just a kidney, long-term patient and kidney graft survival improved for patients who also received a pancreas. Survival rates were 78%–83% for those patients who received only a pancreas or a pancreas some time after a kidney transplant.

As such, roughly 75% of all pancreas transplants are performed along with a kidney transplant (in an SPK procedure) in diabetic patients with renal failure. (About 15% of pancreas transplantation are performed after a previously successful kidney transplantation and 10% consist of pancreas alone in nonuremic patients with very labile and problematic diabetes.) The strategy is to give the patient a healthy kidney and pancreas that is unlikely to contribute to diabetes-related kidney damage in the future. This dual transplant appears to contribute to better survival rates for both organs. After five years, the survival rate for the pancreas in a simultaneous transplant is 70%, while the organ survival rate for other pancreas transplants is only 52%. 

Islet Cell Transplants

Islet cell transplantation (ICT) may eventually become an effective diabetes therapy by replacing whole pancreas transplantations, but at this point, it is experimental and not yet as efficient as pancreas transplantation. ICT involving just those parts of the pancreas, called islets, where insulin is produced. Theoretically, the process is based on the enzymatic isolation of the pancreatic islets from an organ procured from a cadaver donor. The islets obtained are injected into the liver in the recipient via percutaneous catheterization of the portal venous system. This procedure allows the selective transplantation of the insulin-producing cell population, thus avoiding open surgery as well as the transplantation of the exocrine pancreas with related morbidity.

Initial experience with ICT was only modestly promising. The immunosuppression regimen was similar to the one used in solid organ transplantation, based on high dose steroids and calcineurin inhibitors, both of which are agents with diabetogenic effects. Results improved markedly with improved manipulation of the islets and changes in immunosuppression strategy using sirolimus, tacrolimus and daclizumab. This protocol was initiated by investigators at the University of Alberta in Edmonton, Canada. Generally, their protocol requires two islet cell infusions in order to attain the critical cell mass necessary to achieve insulin-independency. The changes in treatment were adopted as the Edmonton Protocol, which is used now in several transplant centers worldwide.

Stem Cell Transplants

Stem cell research allows scientists to explore how to control and direct stem cells so they can grow into other cells, such as insulin-producing beta cells found in the pancreas. Creating new beta cells could lead to cure for type 1 diabetes as they would serve as a replenishable source of cells for islet cell transplantation. They could also provide an additional means for controlling type 2 diabetes.

The American Diabetes Association strongly supports all forms of stem cell research to find effective diabetes therapies, examples of which include embryonic stem cells, cord blood stem cells and adult stem cells.

Researchers have made several advances to demonstrate the potential of human embryonic stem cell (hESC) research and are beginning to understand how this research could benefit diabetes. Already, many of the genes involved in pancreatic development have been identified, and recent discoveries have allowed scientists to overcome the difficult task of getting stem cells to produce the necessary proteins in the correct sequence that will allow them to become insulin-producing islet cells.

Due to the ongoing ethical challenges raised by the use of embryos for stem cell therapies (despite the rescinded funding ban on federally funded embryonic stem cell research), alternatives that avoid these issue have been, and will continue to be investigated aggressively, including cord blood cells and adult stem cells.  Cord blood is obtained from the umbilical cord at childbirth after the cord has been detached from the newborn. This blood contains stem cells, including hematopoietic cells, which can be used in the research of many types of therapies, including diabetes. This includes such studies as the regeneration of islet cells.  Adult stem cells hold promise, particularly as autologously-derived cells that can be directed to differentiate into pancreatic islet cells that, due to their autologous sourcing, will avoid immunogenic response and its complications (and cost) in treatment.

Report #D510 details the status of programs and products in the development for cell-based therapies for diabetes.

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