Could Reversing Inflammation Cure Diabetes?

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Scientists have successfully reversed type 1 diabetes in mice by using adult stem cells and cell surface molecular engineering to reduce the destruction of insulin-producing islet cells.

The key to the breakthrough was introducing adult stem cells, called mesenchymal stem cells, or MSCs, into pancreatic islet cells and reversing the process of inflammation that destroys islet cells and causes type 1 diabetes, according to Dr. Robert Sackstein, Professor of Medicine and co-author of the study conducted at the Harvard-affiliated Brigham and Women’s Hospital, in Massachusetts.

Dr. Robert Sackstein
Dr. Robert Sackstein

“The hypothesis is that the inflammation that destroys islet cells can be controlled by colonizing the pancreas with anti-inflammatory stem cells such as MSCs,” Sackstein said. That realization, however, was only the first step in a complicated process that ended with essentially curing mice of type 1 diabetes.

MSCs are adult stem cells. Similar to embryonic stem cells, MSCs are cells that have yet to develop into a specific type of cell. Because of this trait, they can be differentiated into a variety of cell types. But, even without differentiating into specific cell types, MSCs aid in tissue repair, have immune suppressing qualities, and are anti-inflammatory. MSCs are typically found in a person’s bone marrow, which is how Sackstein, a bone marrow transplant expert, came to turn his attention to use of these cells for treating diabetes.

“We were drawn to the possibility that MSCs placed within islets could inhibit the inflammation incited by the immune response that destroys islet cells and causes diabetes,” Sackstein said.

However, introducing MSCs into islets by direct injection can cause the pancreas to release toxic enzymes that can further damage the islets or, worse yet, can cause profound, life-threatening pancreatic inflammation, Sackstein said. That meant he and his team had to find another way to get MSCs into affected islets.

Their solution was to engineer the surface of the MSC to express a molecule, called HCELL. HCELL is specialized sugar-coated form of a molecule called CD44, and it is the sugar coat itself that directs migration of cells to sites of tissue injury. As such, Sackstein and his team reasoned that sugar-engineering CD44 to create the HCELL molecule on the MSC surface would steer the MSCs toward inflamed islets at the onset of diabetes.

Once the team enforced HCELL expression on the MSCs, they injected the MSC intravenously into diabetic mice. Sackstein and his team observed that the MSCs entered islets without causing any apparent damage. Over time, blood sugar levels in the treated mice were normalized without the use of insulin over a substantial period of time.

“The effect lasted 90 days,” Sackstein said, adding that mice have a lifespan of two years. He also said that it appears at this stage that the HCELL-expressing MSCs could be administered as “many times as necessary.”

While results of the research are certainly encouraging, Sackstein said there are some potential downsides.

“We need to find out whether or not administering a person’s own stem cells can have a deleterious effect on their health,” Sackstein said. “For example, could it support the growth of a cancer? We’re not completely sure at this point.”

He said that once the team has gathered proper safety data on HCELL-expressing MSCs a clinical trial in human beings would be feasible.

“If one were going to perform a clinical trial in type 1 diabetes, it would probably be in in a person who has new-onset type 1 diabetes and is between young adult age and middle age,” he said.

Although Sackstein describes himself as “a bone marrow transplanter”, he actually brings multiple layers of expertise to the field of stem cell research. According to his biography on the website for Sackstein Labs, “[Sackstein] is a basic science immunologist/biochemist/molecular biologist with clinical expertise in internal medicine/hematology/immunology and, in particular, in hematopoietic stem cell transplantation (HSCT).”

Additionally, Sackstein and his team have put in decades of effort to get to a point where MSCs can be clinically tested in humans. Sackstein started working in the field of hematopoietic stem cell transplantation in the 1980s. It was research by his group that first revealed that HCELL molecules could function as a sort of homing mechanism for MSCs.

The anti-inflammatory properties of MSCs not only have potential for treating type 1 diabetes, Sackstein said, but also for treating other acute and chronic autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Sackstein said that in the near future he would be launching a clinical trial on osteoporosis patients in Spain to see how effective MSC treatment might be for that condition. Meanwhile, work on the initial success in reversing type 1 diabetes in mice will continue.

“I’m a scientist so I tend to be conservatively optimistic, to watch my enthusiasm based on observations in animal models,” Sackstein said. “It is ironic that we are exploiting a special sugar modification of the MSC surface (to force HCELL expression) to treat a condition where sugar needs to be regulated. But, to the extent this effect of MSCs is robust and has never been observed before, it’s fantastic. It makes me hopeful that this approach can contribute to a clinical breakthrough in diabetes.”

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Erin May
Erin May

I would love to be the guinea pig

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