Numerous researchers at UCSF are focusing their efforts on stem cell research, in the hopes that it will help generate insulin producing cells for islet transplantation.

UCSF Diabetes Center researcher Michael German, MD is seeking to understand the molecular mechanisms underlying the formation of beta cells and to apply this knowledge to growing beta cells for patients with type 1 diabetes.

Dr. German and his colleagues are convinced that the key to their research is stem cells.  Beta cells are formed from stem cells -- immature cells that have the capacity to mature into any of several different cell types during the development of the pancreas in the fetus.  The pathway from common stem cell to sophisticated beta cell is a step-wise progression involving the orderly activation and repression of specific genes.  Recently, a number of labs at UCSF have been successful in identifying many of these genes and the mechanisms that control their sequential activation.  Dr. German and his colleagues hope to identify which of these genes are involved in directing stem cells to start the process of beta cell differentiation, and to use these genes to force stem cells in the culture dish, or in the intact adult pancreas, to mature into beta cells.

There is strong evidence that this approach may work, as the team has recently shown in fetal mice that one class of genes, the pro-endocrine genes, can force stem cells to mature into alpha cells -- a type of islet cell.  The result is a pancreas made up entirely of these alpha cells.  However, to be successful in humans, the researchers must overcome two hurdles.  They must figure out how to direct the maturing stem cells to specifically become beta cells and not another type of islet cell, and they must have a reliable and safe source of human stem cells.

The team has designed experiments to answer these questions and to overcome possible stumbling blocks.  They believe that this approach will ultimately work if a reliable and safe source of human stem cells is made available, and that it will be possible to grow beta cells from stem cells...and ultimately cure people with type 1 diabetes.

UCSF Diabetes Center researcher Matthias Hebrok, PhD has also made significant contributions to our understanding of pancreas development, and has recently employed the use of a specialized gene-trap technology to screen for pancreatic genes.

In addition, Dr. Hebrok and his colleagues recently found strong evidence that a signaling pathway active in embryonic stem cell development may play a crucial role in both diabetes and pancreatic cancer.  Known as the Hedgehog Pathway, this cascade of chemical steps allows proteins to pass along a signal that ultimately leads to changes in gene activity.  Using human cancer cell lines, Dr. Hebrok and his collaborators have shown that the Hedgehog pathway maintains the extensive proliferation potential of pancreatic tumor cells.  Interestingly, Hedgehog signaling has been shown to maintain stem cell properties in other organs and Dr. Hebrok hopes to control the activity of the Hedgehog pathway to encourage the development of pancreatic beta cells.

Although much more work needs to be done to determine whether the research can be applied to clinical practice, Dr. Hebrok believes that identifying the role of this pathway underscores how studying organ development in embroyos can provide clues to curing diabetes, cancer and other serious diseases.

Because of the novel aspects of the research, the necessity for a network of investigators, and the high costs of the animal studies and human embryonic stem cell experiments, funding from the National Institutes of Health is not an option for many of these studies at UCSF.

In California, there is an effort underway to support stem cell research in California.  For more information, contact www.curesforcalifornia.com