A research team at the Robarts Research Institute in London Ontario Canada led by Dr Mickie Bhatia has successfully used bone marrow stem cells to regenerate damaged pancreases in diabetic mice to cure their diabetes.
The scientists injected bone marrow stem cells into diabetic mice, who were cured or back to normal within seven to 14 days.
But the "most amazing" finding, said Bhatia, is that the stem cells triggered the rodents' damaged pancreases to regenerate on their own.
Here's the surprising part: the stem cells did not integrate into the pancreases of these mice. Instead they somehow triggered the pancreatic cells to become insulin-producing cells. Bhatia's group is now searching for molecules that the bone marrow stem cells might have released to induce the pancreatic cells to repair the damage to the pancreas.
When the researchers injected stem cells into mice with pancreatic damage, the organs were stimulated to repair themselves within 17 days.
Type I diabetes takes literally decades off life expectancy. The greater range of swings in blood sugar that diabetics experience causes their bodies to develop degenerative diseases of old age more rapidly. A human version of this treatment would be very beneficial. If molecular signals are released by the stem cells and can be identified then just those chemicals could be used as therapeutic agents to cure diabetes.
Diamyd Medical's phase II trial was conducted on 47 diabetes patients with the GAD‑based vaccine at the UMAS hospital in Malmoe, Sweden, and St. Gorans Hospital in Stockholm, Sweden. The patients were randomly divided into four groups of approximately 12 patients per group. Each patient received one injection of the vaccine, followed by at least one boost injection four weeks later. Nine patients in every group received the active drug; three received placebo. The groups received different doses of the vaccine, ranging from 4 micrograms to 500 micrograms per dose.
All patients visited the hospitals 10 times during this six-month study. Detailed clinical, immunological and neurological investigations showed no safety concerns at the administered dose levels. The study results show that the diabetes vaccine could significantly protect the patient's ability to secrete insulin, both when fasting and after meals.
The GAD vaccine originated at UCLA from an unexpected convergence of studies in neurobiology and immunology. In the late 1980s, the laboratory of Dr. Allan Tobin, who now directs the UCLA Brain Research Institute, was involved in isolating genes that were thought to be important in brain development and neurological diseases.
Working with Tobin, graduate students Kaufman and Mark Erlander isolated the gene that makes a protein called "GAD," which creates an important neurotransmitter in the brain. At that time, it was known that although GAD was made primarily in the brain, it was also made in the pancreas in the cells that secreted insulin.
Several years later, Kaufman and Tobin realized that the autoimmune response that causes type I diabetes may be due to the immune system attacking the GAD protein in the insulin-producing cells in the pancreas. With this knowledge, they developed a GAD diagnostic test for identifying individuals who were developing type I diabetes based on antibodies in their blood that recognized GAD.
Kaufman, in his own laboratory at the UCLA Department of Molecular and Medical Pharmacology, along with Dr. Jide Tian, of the same department, searched for ways to help the immune system tolerate the GAD protein, which would circumvent or inhibit the autoimmune attack.
The team reported in the journal Nature in 1993 that when young, diabetes-prone mice were treated with a small amount of the GAD protein, their immune systems learned to tolerate the protein. The autoimmune response that leads to type I diabetes never developed in these mice as they grew older.
In another study published by Nature-Medicine in 1996, the UCLA team developed the GAD vaccine to inhibit the autoimmune response after it had already begun to attack the insulin‑producing cells. Kaufman and Tian showed that even after the type I diabetes disease process had started in diabetes-prone mice, its progression could be inhibited by the GAD vaccine.
According to Tian, the GAD vaccine activated T-cells (a type of white blood cell or immune defense cell) that recognized GAD. The T-cells traveled to the pancreas and, recognizing the GAD protein, released calming substances called "anti-inflammatory" cytokines, which suppressed the immune cells that were killing the insulin-producing cells.
"The beauty of this vaccine is that it just affected one small part of the immune system — without broadly inhibiting the function of the entire immune system," Tian said.
For people who already have type I (the kind that comes when one is young) diabetes this is probably a necessary treatment in addition to a treatment that will get the pancreas producing insulin again. Otherwise a pancreas that starts producing insulin will likely come under auto-immune attack again.
Update: Also see a January 2004 report that reports how infection of mice with lymphocytic choriomeningitis virus (LCMV) in the early stages of diabetes stops the autoimmune response.
Viruses can both cause and prevent autoimmune disease. In order to understand this dualism, Matthias von Herrath and colleagues from the La Jolla Institute for Allergy and Immunology in California exposed prediabetic mice to viral infections. In the January 2 issue of the Journal of Clinical Investigation the authors report that infection with lymphocytic choriomeningitis virus (LCMV) during the prediabetic period completely abolished the diabetic process in two distinct mouse models.
This protection against the development of type 1 diabetes correlated with a reduced number of autoaggressive CD8 T cells in pancreatic islets. Increased production of the chemokine CXCL-10 in pancreatic lymph nodes redirected cells of the immune response away from the b cells. Once in the pancreatic lymph node, CD8 lymphocytes underwent increased apoptosis, which was directly dependent on TNF-a and indirectly on IFN-g production. The data indicate that proinflammatory cytokines and chemokines induced by viral infection can influence ongoing autoaggressive processes beneficially at the preclinical stage if produced at the correct time, location, and level. Therefore viruses that do not directly destroy b cells may actually enhance the course of autoimmune diabetes.
|Share |||Randall Parker, 2003 June 23 07:56 PM Biotech Therapies|