A research team studying mesenchymal stem cells (MSCs) – a cell type useful for the treatment of immune-related diseases — have uncovered a way to enhance and prolong the therapeutic effects of these cells in a preclinical model of type 1 diabetes. The team, led by Robert Sackstein, MD, PhD, of BWH’s Departments of Dermatology and of Medicine, and Reza Abdi, MD, of the BWH Department of Medicine and Transplantation Research Center, reports its results this week in the journal Stem Cells.
In type 1 diabetes, the body’s immune cells obliterate pancreatic islets, the sites of insulin production. Mesenchymal stem cells (MSCs) are a type of adult stem cell that have potent immune-suppressing and anti-inflammatory effects. In pre-clinical trials using diabetic-prone mice (non-obese diabetic [NOD] mice), researchers had previously found that intravenous administration of MSCs can dampen pancreatic injury, reducing the levels of sugar in the bloodstream of the diabetic mice and avoiding insulin administration, but these effects were modest and temporary. Sackstein and his team hypothesized that if more MSCs could be forced to populate within the pancreatic islets, more islets could be spared from immune destruction, yielding a more complete reversal of diabetes.
MSCs normally lack a key cell surface adhesion molecule called “HCELL” that mediates homing of cells in the bloodstream to sites of tissue inflammation. The injection of MSCs directly into pancreatic islets is not feasible because the pancreas is fragile and releases highly toxic enzymes when manipulated. The research team thus needed to devise a way to drive the navigation of intravenously administered MSCs to the sites of the immune attack. To do so, they engineered the display of the HCELL homing molecule to steer them toward the inflamed pancreatic islets.
The team found that administration of the HCELL-bearing MSCs into diabetic mice caused the MSCs to lodge in the islets, leading to a sustained reversal of diabetes: there was durable normalization of blood sugar levels, eliminating the need for insulin administration.
“This preclinical study represents an important step in the potential use of mesenchymal stem cells in the treatment of type 1 diabetes and other immune-related diseases,” said Sackstein, co-corresponding author of the study. “While further studies of the effects of MSCs are warranted, the results are extremely promising in providing a strategy to enhance the utility and effectiveness of MSC-based therapy for clinical use in a wide variety of inflammatory conditions.”