The Diabetes Center at the University of California, San Francisco (UCSF). has one mission: to advance the care and treatment of patients with type 1 and type 2 diabetes worldwide so that they may achieve the ultimate goal of bringing an end to the disease.
Their organization was born from the devastation of diabetes, the clinical and educational needs of patients, and the firm belief that scientific insights into the causes of diabetes will lead to a cure.
Center Director Matthias Hebrok, PhD, and fellow researcher Mark Anderson, MD, PhD, have created a highly productive partnership that resulted in the reengineering of a human thymus from embryonic stem cells. Defects in the function of the thymus are part of the explanation for autoimmune diseases such as type 1 diabetes.
The thymus is an important organ that instructs the immune system to be “tolerant” of transplanted tissues – and to know the difference between self and non-self. The goal of these studies is to test if transplanted cell rejection will be prevented -- if stem cells from the same donor are used to create both a thymus and specialized types of cells such as insulin-producing beta cells.
Thymus regeneration may have tremendous implications for future therapies that are aimed at treating or reversing type 1 diabetes and other autoimmune diseases.
UCSF has achieved many milestones on the way to its goal of bringing an end to the disease. Here are 3 important milestones where stem cells played a crucial role:
Generating Beta Cells from Human Embryonic Stem Cells
Michael German, MD and Matthias Hebrok, PhD have made significant contributions to the fields of beta cell development, pancreas development, and stem cell research. Dr. German is seeking to understand the molecular mechanisms underlying the formation of beta cells and to apply this knowledge to growing beta cells for individuals with type 1 diabetes. In particular, he hopes to identify the genes involved in directing stem cells to begin the process of beta cell differentiation.
By studying how beta cells develop in the embryonic pancreas, Dr. Hebrok is identifying new approaches to regenerating these cells. Dr. Hebrok is also developing new methods for coaxing embryonic stem cells to differentiate into fully functional beta cells. By replicating the signaling events during pancreas development in cell culture, he hopes to optimize the formation of definitive endoderm—the germ layer that gives rise to beta cells from embryonic stem cells—ultimately generating fully functional beta cells.
Through his work with one particular embryonic signaling pathway called Hedgehog, Dr. Hebrok was responsible for a breakthrough discovery in pancreatic cancer in 2003 —demonstrating the important research linkages between diabetes, cancer and other diseases.
Reprogramming Stem Cells to their Embryonic State
Embryonic stem cells reside in the early mammalian embryo and have the ability to give rise to all cell types in the body, hence they are called pluripotent. Miguel Ramalho-Santos, PhD is studying how the pluripotent nature of embryonic stem cells is genetically regulated, and how it might be possible to tailor the differentiation of these cells to particular cell types such as beta cells.
In 2007, Dr. Santos and his colleagues reported an improved technique for genetically reprogramming mouse cells to become embryonic stem cells. By over-expressing a combination of genes in mouse skin cells, the mouse cells began to lose their adult functions and function like they did in their embryonic state.
The next step— perfecting cell reprogramming in human cells—will help in the study of human disease development and may lead to the creation of patient-specific stem cell based therapies. Once patient-matched embryonic stem cells can be generated, the risk for rejection upon transplantation is much reduced.
The Role of Inflammation
Inflammation is a biological process driven by the immune system to help the body react to infection, irritation or other injury—and help the body to repair itself.
In 2000, Douglas Hanahan, PhD and his colleagues discovered that chronic tissue inflammation may paradoxically serve to fuel rather than reduce tumor growth in cancer. He believes MMP9, a protein secreted by inflammatory mast cells of the immune system, are actually driving the processes of cancer development.
By eliminating MMP9, the incidence of full- blown cancer is dramatically reduced, proving that the immune system is contributing to the development of cancer.
Dr. Hanahan continues to focus on the genetics of both cancer and autoimmunity. By studying the process of inflammation, he will better understand how this process plays a role in the autoimmune attack of the beta cells. Additionally, inflammation has been known to disrupt the body’s ability to process insulin, contributing to the onset of type 2 diabetes.
Learn more about how you can take advantage of these and future breakthroughs in diabetes research by saving your stem cells in a safe, effective manner: