What the research says...
As we move well into the 21st Century, research continues to show that stem cells can be considered an effective alternative treatment for Diabetes. Recent research from the Harvard Stem Cell Institute in Massachusetts has got the world talking about the effectiveness of this alternative diabetes treatment compared to more ineffective traditional practices. Before we get to this lets give a brief overview of Type 1 and 2 Diabetes.
Type 1 diabetes is a chronic illness as a result of the body’s inability to produce insulin due to the autoimmune destruction of the beta (islet) cells in the pancreas. The pancreas has two major types of cells; exocrine for the production of enzymes to digest food and endocrine for the production of insulin in the beta cells. Specifically, Type 1 DM is the end result of lymphocytic (white blood cells) infiltration and destruction of insulin-secreting beta cells of the islets of Langerhans in the pancreas.
Approximately 85% of type 1 DM patients have circulating islet cell antibodies, and the majority also have detectable anti-insulin antibodies.The most commonly found islet cell antibodies are those directed against glutamic acid decarboxylase (GAD), an enzyme found within pancreatic beta cells.
As beta-cell mass declines with destruction of the cells, insulin secretion decreases until the level of available insulin is no longer adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycemia develops leading to type 1 diabetes. Patients need injectable insulin to reverse the excess blood glucose to prevent the complications such as ketosis, decrease excess glucagon secretion from the liver, and normalize lipid and protein metabolism.
The absence of insulin is life-threatening and requires diabetic patients to take daily hormone (insulin) injections. However, insulin injections do not adequately mimic beta cell function. This results in the development of diabetic complications such as neuropathy, nephropathy, retinopathy, and diverse cardiovascular disorders.
Unlike type 1 DM, type 2 DM is the result of insulin resistance, inadequate insulin secretion, and excessive or inappropriate glucagon secretion; all of which result in elevated blood glucose levels. The condition is the result of genetics and from a variety of lifestyle choices such as excessive caloric intake, inadequate caloric expenditure, obesity, and lack of exercise. The management options include dietary changes, exercise, and weight loss. Avoiding simple sugars and carbohydrates is key, and always pairing a protein with a complex carbohydrate to maintain steady blood glucose levels are key. The most important long-term maintenance strategy is weight loss and regaining the ideal BMI. Insulin sensitizers, such as metformin, may be needed to maintain normal blood glucose levels. Rarely, insulin is needed in type 2 DM.
Protocols have been developed that promote the formation of pancreatic endocrine cells from human pluripotent Stem Cells, encompassing both embryonic stem cells and induced pluripotent Stem Cells.
This new method for generating hundreds of millions of insulin-producing pancreatic beta cells from human pluripotent stem cells is considered a major step toward a diabetes cure.
A paper was published in the October 9 issue of Cell by a group of researchers from the Harvard Stem Cell Institute in Massachusetts and led by department co-chair Dr. Douglas A Melton, the Xander University Professor at Harvard.
The results suggested that stem-cell-derived beta cells present an opportunity for cell therapy to treat the disease. Because of the limited supplies of donated cadaveric islet cells and the very small amount of human beta-cell replication achieved in vitro, the supplies of human beta-cell supplies are limited.
Now, a generation of an unlimited supply of human beta cells could extend this therapy to millions of new patients and could be an important test case for translating stem-cell biology into the clinic.
Using a human embryonic stem-cell line and two human-induced pluripotent stem-cell lines, the team applied a novel 4- to 5-week scalable differentiation protocol to generate hundreds of millions of glucose-responsive beta cells in vitro that lowered glucose levels when transplanted into diabetic mice.
Some of the stem-cell-derived beta-cell batches secreted as much insulin as cadaveric islets. Dr. Melton’s team is now "starting experiments on monkeys, but they do not anticipate human trials for at least three years.
Dr. Robert E Ratner, chief scientific and medical officer for the American Diabetes Association, explains that the results are important because the team was able to use both human pluripotent stem cells and embryonic stem cells to generate a large volume of beta cells that can be used for testing.
He said that the beta-cell volume generated per batch is about 300 million and may still not be high enough for one human transplant, which requires about 500 million, but he says that it is the highest levels done to date.
Also, it's not known how long the cells will last after transplantation. It could be a week, a month, no one knows. And there needs to be a method for protecting the cells from rejection due to the autoimmunity issue. The injected cells may need protection by immunosuppression, encapsulation, or masking the harmful proteins on the cells that cause rejection, known as antigens, prior to injection.
Dr. Melton and his team are currently investigating two ways of protecting the beta cells from immune attack. They are collaborating with scientists at the Massachusetts Institute of Technology to develop microcapsules to protect the clusters of cells. To treat one human, hundreds of thousands of these microcapsules will be required.
"The other 'device' uses a large membrane into which millions of cells are placed before injection into the body.
Besides embryonic stem cells, adult stem cells offer an advantage because they are immune compatible and do not risk rejection by the recipient.
In addition to the pancreas as a source of islet cells, the liver is derived from embryonic endoderm, and it may represent a viable source of Adult Stem Cells (ASCs) capable of generating insulin-producing cells. Likewise, liver stem cells, such as oval hepatic cells, can be thought of as another possible source for insulin-producing cells.
Altogether, studies suggest the potential use of autologous liver biopsies as a source of ASCs to generate functional islet-like structures for insulin-producing cell replacement in diabetes.
Mesoderm-derived bone marrow is another important reservoir of ASCs in adults, and it may represent an alternative source of ASCs that can circumvent many of the problems associated with hepatic cells in the production of insulin-producing cells.
These cells, called MAPCs (multipotent adult progenitor cells), can be expanded in vitro and differentiated to cells positive for ectodermal, mesodermal, and endodermal lines.
However, the isolation of insulin-containing cells from MAPCs has not yet been reported.
Alternatively, one report showed the possibility of using highly purified bone marrow stem cells for pancreas repopulation.
Monocytes from peripheral blood also may represent an alternative source. Monocytes appear not to be committed to becoming terminally differentiated cells of the bone marrow but can be reprogrammed to insulin-containing cells.
Several studies have documented the potential of pancreatic duct epithelium (lining of the ducts) to differentiate in vitro into islet-like structures, suggesting that this is a candidate location for islet progenitors in the adult pancreas.
Most studies on beta-cell differentiation from adult stem cells are based on mesenchymal stem cells (MSCs), which were originally identified in the bone marrow and considered multipotent, and can be easily derived from virtually any organ or tissue in the body, perhaps except for peripheral blood.
Embryonic Stem Cells and Adult Stem Cells for pancreatic differentiation focuses on the utilization of embryonic and adult stem cell types for the procurement of transplantable insulin-producing cells. The ASCs will include sections on bone marrow cells, umbilical cord blood stem cells, ductal cells, and mesenchymal stem cells. Another process to develop insulin-producing cells is called trans-differentiation, which is an intriguing phenomenon by which terminally differentiated cells from other tissues might be induced to alter their function to become islet-like cells.
At one point, it was thought that mesenchymal cells could be as pluripotent as their embryonic counterparts. The general view, being that they are mesodermal in origin, these cells might require more than simple protocols to force their differentiation into endodermal and ectodermal lineages needed for insulin-producing beta cells.
Clearly these are exciting times for sufferers looking for an alternative treatment for diabetes that has been shown to be effective and goes a long way to explaining why so many are seeking Stem Cell Treatment to tackle this debilitating affliction. Contact the Stemaid Institute Europe today for more information on stem cell treatment for diabetes.
Ungefroren H, Fändrich F.Adv Exp Med Biol. 2010; 654:667-82.