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BWH Stem Cells

Steering Stem Cell Trafficking Into Pancreas Reverses Type 1 Diabetes

BWH Stem CellsResearchers develop ‘GPS’ method to guide mesenchymal stem cells to inflammatory sites.

Researchers at Harvard-affiliated Brigham and Women’s Hospital (BWH) studying mesenchymal stem cells (MSCs) — a cell type useful in treating immune-related diseases — have uncovered a way to enhance and prolong the cells’ therapeutic effects in a preclinical model of type 1 diabetes.

The research team, led by Harvard Medical School (HMS) Professor Robert Sackstein of BWH’s Departments of Dermatology and of Medicine and HMS Associate Professor Reza Abdi of BWH’s 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, where insulin is produced. MSCs are a type of adult stem cell with potent immune-suppressing and anti-inflammatory effects. In preclinical trials using diabetic-prone mice (non-obese diabetic mice), researchers had previously found that intravenous administration of MSCs could dampen pancreatic injury by reducing the levels of sugar in the mice’s bloodstreams without insulin administration, but these effects were modest and temporary.

Sackstein and his team hypothesized that if more MSCs could be forced to populate inside 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, which mediates the 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. To get intravenously administered MSCs to the sites of the immune attack, the research team engineered the HCELL homing molecule to steer them toward the inflamed pancreatic islets.

The team found that administering HCELL-bearing MSCs into diabetic mice caused the MSCs to lodge in the islets. The result was durable normalization of blood sugar levels, eliminating the need for insulin administration — a sustained reversal of diabetes

Sackstein, co-corresponding author of the study, concluded that while further studies of the effects of MSCs are warranted, the 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.

 

from the Harvard Gazette

http://news.harvard.edu/gazette/story/2015/01/steering-stem-cell-traffic…

 

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Role of the integrated stress response in type 1 diabetes pathogenesis
In individuals with type 1 diabetes (T1D), the insulin-producing beta cells are spontaneously destroyed by their own immune system. The trigger that provokes the immune system to destroy the beta cells is unknown. However, accumulating evidence suggest that signals are perhaps first sent out by the stressed beta cells that eventually attracts the immune cells. Stressed cells adapt different stress mitigation systems as an adaptive response. However, when these adaptive responses go awry, it results in cell death. One of the stress response mechanisms, namely the integrated stress response (ISR) is activated under a variety of stressful stimuli to promote cell survival. However, when ISR is chronically activated, it can be damaging to the cells and can lead to cell death. The role of the ISR in the context of T1D is unknown. Therefore, in this DRC funded study, we propose to study the ISR in the beta cells to determine its role in propagating T1D.
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