Brigham and Women’s Hospital Researchers Reverse Type 1 Diabetes in Diabetic Mice

Brigham and Women’s Hospital (BWH) is a Harvard University-affiliated institution with a robust research program. In particular, several BWH are interested in mesenchymal stem cells and their ability to suppress inflammation and mediate healing in injured organs.

To that end, a research team led by Robert Sackstein from BWH’s Departments of Dermatology and of Medicine and Reza Abdi from BWH’s Department of Medicine and Transplantation Research Center, has published a stupendous report in the journal Stem Cells. In this paper, Sackstein and his coworkers used mesenchymal stem cells (MSCs) to successfully treat laboratory animals that suffered from type 1 diabetes.

Type 1 diabetes is, to a large extent, a disease of the immune system, since a large majority of type 1 diabetes patients have immune cells that recognize the insulin-secreting beta cells as foreign and these immune cells attack and obliterate them. MSCs are a type of adult stem cell that has shown potent immune-suppressing and anti-inflammatory effects in animal and human clinical studies. Previous preclinical trials with diabetic-prone mice have demonstrated that intravenous administration of MSCs can tamp down pancreatic injury and reduce the blood sugar levels without insulin administration. However, these effects were modest and temporary.

Sackstein and his team suggested that if more MSCs could be inserted into the pancreatic islets, then more islets would be spared from immune destruction. This would yield a more complete reversal of diabetes.

MSCs tend to lack a key cell surface adhesion molecule called HCELL. HCELL mediates the homing of cells in the bloodstream to inflammatory sites. Unfortunately, direct injection of MSCs directly into pancreatic islets is not clinically feasible because the pancreas is fragile and the damage caused by injection would cause the release of hydrolytic enzymes that would degrade the rest of the pancreas and other tissues as well. In order to move intravenously administered MSCs to the sites of the immune attack, Sackstein and others engineered MSCs that expressed the HCELL homing molecule. The presence of HCELL on the surfaces of these MSCs directed them to the inflamed pancreatic islets.

The BWH team found that administering these HCELL-bearing MSCs into diabetic mice caused the MSCs to lodge in the islets. These cells decreased inflammation in the pancreas and durably normalized blood sugar levels in the mice, which eliminated the need for insulin administration; in other words they caused a sustained reversal of diabetes

Sackstein concluded that while further studies of the effects of MSCs are warranted, 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.