Dec. 10, 2003 San Diego, Calif. (December 8, 2003) -- Millions of Americans are diagnosed with type I diabetes every year. The disease, which results from the body's failure to produce insulin, continues to be a mystery to the medical community, although both genetics and environmental factors appear to play a role in the cause. Type 1 diabetes is usually diagnosed in children or young adults and, if not properly treated, can lead to complications such as heart and kidney disease, stroke, amputations, blindness, and even death. Advancements in research continue to move steadily toward an eventual cure through the use of breakthroughs such as cellular therapy and bone marrow transplantation, as shown by several studies presented during the 45th Annual Meeting of the American Society of Hematology.
"As researchers seek out a possible cure for type 1 diabetes, stem cell therapy and bone marrow transplantation are important avenues of exploration," said Janis Abkowitz, M.D., Head of the Hematology Section, University of Washington Medical Center and Professor of Medicine, University of Washington, Seattle. "Although we have a long way to go, this field shows promise."
Derivation of Functional Insulin Producing Cells From Human Bone Marrow-Derived Stem Cells (Abstract 750)
Insulin dependent type 1 diabetes is an autoimmune disorder, meaning the body's own immune system attacks native cells and tissue because it recognizes the material as foreign matter. In the case of type 1 diabetes, insulin producing beta cells that are found in the pancreas are destroyed by the body's own T-cells, a natural immune response gone haywire. In an attempt to circumvent this troublesome immune response, potential cellular therapies, such as islet (endocrine) cell transplantation, have recently been explored through research. However, even these novel therapies are hampered by islet donor availability, immune rejection, and an inability to replicate the result in multiple animal models.
A study conducted by Lijun Yang, M.D., and researchers at University of Florida used bone marrow-derived stem cells to determine whether or not they could ultimately lead to insulin-producing cells through in vitro (in an artificial environment) trans-differentiation. Recent research has indicated that adult bone marrow is a potential source for cells with pluripotent differentiation capacity, or the ability to give rise to any number of differentiated cell lines.
"Human bone marrow is an ideal source for stem cells because it is readily available and easily secured with a relatively simple procedure," said Dr. Yang. "Also, bone marrow-derived stem cells may not have the same antigen as pancreatic beta cells, which would eliminate the potential for rejection or a negative immune response after cellular implantation."
Results from this study showed that human bone marrow-derived single stem cell lines demonstrated an ability to proliferate and differentiate in vitro. These cells were induced through in vitro culture conditions to differentiate into islet like cells that were capable of glucose-related insulin production, with confirmed expression through RT-PCR (reverse transcription-polymerase chain reaction) of multiple genes known to be related to pancreatic beta cell development and function. Researchers implanted these islet-like cells into the spleen and kidney capsule of an NOD-SCID (non-obese diabetic-streptozotocin-induced diabetic) mouse model with a blood sugar level of 400 mg/dL. They monitored the diabetic mouse's glucose level for up to 56 days and observed an apparent reduction in glucose levels after two weeks.
"Our findings show that human bone marrow-derived stem cells may serve as a potential autologous source for cell therapy in the treatment of patients with type 1 diabetes," said Dr. Yang. "This means that we may one day be able to use a person's own stem cells to reverse their diabetes."
Hematopoietic Stem Cell Transplantation Allows for Tolerance for Allogeneic Islets But Does Not Significantly Contribute to Organ Regeneration (Abstract 746)
Hematopoietic stem cell transplantation is known to cure many disorders such as leukemia and certain cancers, bone marrow failure syndromes, and genetic diseases. The body uses stem cells to replace cells that have been damaged or killed. Recent research examines this still burgeoning bone marrow transplant technology for potential application in the field of diabetes. A study led by Elizabeth Kang, M.D., and researchers at the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health sought to determine whether or not bone marrow transplantation and full donor hematopoietic engraftment could give rise to insulin-producing pancreatic islet cells. Results showed that the capacity of hematopoietic cells to regenerate the pancreas, without additional manipulation, was unsuccessful. However, results did show that implanted islet cells seemed well tolerated in mice receiving bone marrow transplants.
Using a NOD (non-obese diabetic) mouse model with naturally occurring autoimmune diabetes, researchers performed bone marrow transplants prior to, at the onset of, and two weeks beyond the development of diabetes. Expected age of diabetes onset in these mice is 12 to 16 weeks. Bone marrow recipients were then monitored for the onset or presence of diabetes. Of the eight mice that were fully engrafted prior to the onset of diabetes, all appeared symptom free beyond one year of follow-up. In contrast, mice that failed to achieve full engraftment of the bone marrow transplant developed or remained diabetic. Those mice that successfully engrafted at or after onset of diabetes also remained hyperglycemic.
To gauge whether or not tolerance to islet cell transplantation was achieved, mice that had undergone successful hematopoietic transplantation, characterized by full engraftment, were injected intraperitoneally (in the abdominal cavity) with a minimum of 300 islet cells obtained from the same allogeneic (of the same species, but genetically different) donor strain as the hematopoietic cells. Results showed two of four mice that had undergone hematopoietic transplantation followed by islet transplantation seemingly experienced a reversion of their diabetes, however the four controls that received islets without prior hematopoietic transplantation remained diabetic.
"The results of this study were negative in that we did not see regeneration of islet cells after bone marrow transplantation alone, but we did confirm tolerance to islet cell grafts," said Dr. Kang. "Without further manipulation, bone marrow transplantation in and of itself will not cure diabetes, but this method still holds promise and could potentially unlock doors leading to future progress in the field of cell therapy-derived cures for diabetes."
The American Society of Hematology is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
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