15 January 2015

Self-guided stem cells against diabetes

"GPS navigation" for stem cells

NanoNewsNet based on materials from Harvard University: Steering stem cell trafficking into pancreas reverses type 1 diabetes

Scientists from Brigham and Women's Hospital, the clinical base of Harvard University, studying mesenchymal stem cells (MSCs), a type of cells potentially suitable for use in the treatment of autoimmune diseases, have found a way to enhance and prolong the therapeutic effect of these cells in a preclinical model for the treatment of type 1 diabetes mellitus.

In type 1 diabetes, the immune cells of the body destroy the pancreatic islets, the cells of which produce insulin. Mesenchymal stem cells are a type of adult stem cells that have a powerful immunosuppressive and anti-inflammatory effect. Previously, in preclinical experiments on mice predisposed to diabetes, researchers found that intravenous administration of MSCs can mitigate damage to the pancreas by lowering blood sugar levels without insulin, but these effects were insignificant and temporary.

The head of the study is a professor at Harvard Medical School Robert Sackstein, MD, PhD, and his colleagues suggested that if the pancreatic islets are populated with a large number of MSCs, immune destruction will affect a smaller number of islets, which will provide a more pronounced retreat of the disease.

Normally, MSCs do not carry on their surface a key adhesion molecule called HCELL, which mediates the homing of cells in the blood into areas of tissue inflammation. The introduction of MSCs directly into the pancreatic islets is not possible, because the pancreas is extremely fragile and releases highly toxic enzymes with any manipulation. In order to direct intravenously injected MSCs to sites that had been subjected to an immune attack, in this case to inflamed pancreatic islets, the researchers "forced" these cells to express the HCELL homing molecule.

Mesenchymal stem cells (green) colonize the pancreatic islet.
The blue dots are the nuclei of the islet's own cells. (Photo: Robert Sackstein)

Experiments on mice with an autoimmune diabetes model have shown that the expression of HCELL molecules on the MSCs surface led to a more efficient colonization of islets. The result was a steady normalization of blood sugar levels, eliminating the need for insulin administration, in other words, a prolonged retreat of diabetes.

According to Professor Saxtein and his colleagues, although the effects of MSCs require further study, this preclinical study represents an important step in the potential use of mesenchymal stem cells in the treatment of type 1 diabetes mellitus and other immune-related diseases.

The original article was published in the journal Stem Cells: Abdi et al., HCELL Expression on Murine MSC Licenses Pancreatotropism and Conferences Durable Reversal of Autoimmune Diabetes in NOD Mice.

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