Dr. Yong Zhao: Stem Cell for Diabetes Study

People who have type 1 diabetes have dysfunctional immune systems that attack and destroy beta cells in the pancreas that create insulin. The body’s cells use insulin as a chemical switch to control glucose levels, like a “valve” that switches on or off to allow or stop glucose from entering cells.

Without insulin, people with type 1 diabetes are forced to ride a dangerous blood sugar rollercoaster, with high blood sugar levels making them feel fatigued and low levels bringing blackouts and seizures.

To guard against this, people with type 1 diabetes depend on a daily insulin injection or an insulin pump. Without either, their blood sugar levels would fluctuate uncontrollably and they would risk organ failure and death.

Thus, any treatment that hopes to cure or reverse type 1 diabetes hinges on halting the autoimmune attack on the pancreas, say researchers from the University of Illinois. The researchers claim to have developed a cord-blood stem-cell treatment that does just that.

“The inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes,” the researchers, led by Dr. Yong Zhao, write in a paper published in the Jan. 9 issue of the open-access journal BMC Medicine. Dr. Zhao is an assistant professor at the University of Illinois’s endocrinology, diabetes and metabolism departments. He also specializes in endocrinology, stem cells and immunology.

The University of Illinois team says their new, experimental stem cell treatment for people with type 1 diabetes involves “teaching” impaired immune system cells to stop attacking the insulin-producing cells in the pancreas. This allows the organ to start producing insulin again.

Calling it the “Stem Cell Educator therapy,” the team said the therapy offers the promise of a new approach to overcome the autoimmunity underlying type 1 diabetes.

Stem Cell Educator therapy involves treating a type 1 diabetic’s T-cells with stem cells taken from human cord blood to help jumpstart pancreatic insulin production. Stem cells are derived from cord blood, or the excess blood taken from the umbilical cord or placenta of a newborn baby.

In the therapy, a patient’s immune system cells are combined with the cord blood stem cells (CB-SCs), and researchers found that the CB-SCs seem to “re-educate” the patients’ T-cells to stop attacking the pancreas cells.

In their paper, the researches write: “We developed a procedure for Stem Cell Educator therapy in which a patient’s blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient’s circulation.”

“Initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of islet beta cells,” they added.

Dr. Zhao’s team was surprised to find that the treatment worked even in people with long-standing diabetes who were believed to have no insulin-producing ability.

15 participants, 4 exams, 3 factors
The study involved 15 patients from China’s General Hospital of Jinan Military Command in Shandong. Study participants were between 15 to 41 years old and had been living with type 1 diabetes for an average of nine years. Twelve of the participants were given the treatment, while the three were made up the control group.

Blood was extracted from the 12 participants, the T-cells were separated and pumped into a device the researchers call a “stem cell educator” where T-cells were exposed to cord blood stem cells for three hours. The T-cells were then pumped back into the participants’ blood.

The patients were examined four times after the treatment: at four weeks after, at 12, at 24 and at 40 weeks later.

During exams, researchers measured C-peptide (a protein fragment that’s a byproduct of insulin production), beta cell function and A1C levels.

Their findings?

C-peptide: The educator therapy group had improved levels of C-peptide at 12 weeks, and this continued to improve until 24 weeks and remained stable through the follow-up at 40 weeks. Participants in the control group showed no changes in C-peptide.

Beta cell function: The average daily dose of insulin dropped nearly 39 percent after 12 weeks for participants in the group with some beta cell function; by 25 percent among participants without beta cell function.

A1C levels: A1C levels indicate average blood sugar levels over two to three months, and doctors advice people with type 1 diabetes to maintain A1C levels below seven percent. Even a drop of just one percent in A1C levels can reduce the risk of health complications. The average hemoglobin A1C level dropped 1.06 percent for those with residual beta cell function; it dropped 1.68 percent for those without beta cell function.

“Evidence that human cord blood-derived multipotent stem cells (CB-SCs) can control autoimmune responses by altering regulatory T-cells (Tregs) and human islet beta cell-specific T-cell clones offers promise for a new approach to overcome the autoimmunity underlying type 1 diabetes,” the researchers write in their paper.

“Stem Cell Educator therapy is safe, and in individuals with moderate or severe type 1 diabetes, a single treatment produces lasting improvement in metabolic control.”

“Our study brings a new hope for people with type 1 diabetes. If we can control the autoimmunity, we may reverse the disease. We showed that the islets [cells] can start to work again,” says Dr. Yong Zhao,

Noting the raging controversy over the use of human embryonic stem cells (hESCs), the team writes: “Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases—without the safety and ethical concerns associated with conventional stem cell-based approaches.”

Currently, many other autoimmune diseases like lupus and rheumatoid arthritis have no treatment.

Dr. Zhao’s plans?
Meanwhile, Zhao plans to do another study with patients having multiple treatments to see if it’s possible to reverse the loss of insulin production function fully.

He’s also pursuing some clinical trials on type 2 diabetes patients—the more common type that affects 154 million people worldwide, and costs countries millions of dollars yearly on healthcare and lost productivity. In this type, the pancreatic islet can make insulin but the liver is resistant to it and not picking it up.

This kind of insulin resistance is associated with immune dysfunction, Dr. Zhao said. “You can use the Stem Cell Educator therapy to crack their immune dysfunction and overcome the insulin resistance.”

Dr. Zhao is currently conducting a trial on 25 patients. The results are “exciting,” but the study has not yet concluded. “This will open a new research field for both Type 1 and Type 2 diabetes,” Dr. Zhao said.

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