In Type 1 diabetes, the body's immune system turns against itself, destroying pancreatic beta cells. These cells produce insulin, a hormone that controls the amount of sugar in the blood stream. In Type 2 diabetes, caused by lifestyle factors such as obesity, the body's ability to respond to, or produce insulin is reduced. In both cases, without insulin, blood sugar can increase to toxic levels. While pharmaceutical insulin is commonly used to control diabetes, it does not sufficiently replace beta cells, and the adverse short- and long-term effects of diabetes remain.

The diabetes disease team has developed a strategy in which they prompt human embryonic stem cells to differentiate into islet progenitor cells in the lab and then transplant the cells into rodents, where they differentiate into mature, insulin-producing beta cells.

To prevent the immune system's reaction to the cells -- either the auto-immune attack that would continue to occur in Type 1 diabetics or the normal immune system rejection to foreign cells that occurs in any transplant setting - the team has explored two strategies. One involves administering the cells inside a simple device, implantable under the skin. The other involves using next-generation pharmaceuticals, some of which have been approved recently by the FDA, that enable transplantation between unmatched individuals without major side effects.

The work will include identifying the best means for introducing cells into patients.

Brain Tumor Disease Team grant

The brain tumor disease team will derive human adult and fetal neural stem cells and mesenchymal stem cell lines, each cell line having been proffered as therapeutic, but never having been compared head-to-head in treating tumors. Each cell line will be modified using two therapeutic genes. One of the genes expresses a protein known as TRAIL that specifically kills tumor cells, but does not harm normal cells and tissues. The other expresses cytosine deaminas, an enzyme that converts a non-toxic chemical into a toxic chemotherapeutic.

The goal is to identify the most effective neural stem cell and therapeutic gene combination to advance for clinical trial in patients with brain tumors.

"These studies are a vital opportunity to explore the behavior of stem cells in patients," says Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Source: University of California - San Francisco