The bone marrow transplant is a stem cell success story. That procedure, in which blood stem cells from a donor form the beginnings of a new immune system for patients with leukemia or lymphoma, has saved countless lives — including thousands at City of Hope.
Hsun Teresa Ku, Ph.D., a new assistant professor in the Department of Diabetes, Endocrinology & Metabolism, thinks that stem cell approaches similar to those developed to manipulate blood stem cells, called hematopoietic stem cells, could be used to replace a different damaged tissue: pancreatic cells lost in type 1 diabetes.
Ku brings the expertise she gained working with blood stem cells as a graduate student to this task. “In doing these experiments we are trying to emulate approaches taken with these cells 40 years ago,” she said.
In type 1 diabetes, an autoimmune disease most common in children, the body destroys its own insulin-producing cells in the islets of the pancreas. Insulin is a hormone that allows cells to use glucose for energy. Since people with type 1 diabetes cannot produce their own insulin, they must inject insulin and regularly monitor their blood glucose levels. Today, type 1 diabetes has no cure, and patients follow this regime for a lifetime.
About one in every 400 to 600 children and adolescents has type 1 diabetes, according to the Centers for Disesase Control and Prevention.
One investigational treatment, the transplantation of islet cells from a donor, is already performed at City of Hope, which has been designated one of 14 islet cell transplant centers in the United States by the Juvenile Diabetes Research Foundation.
For that promising transplantation procedure, insulin-producing islet cells are removed from a cadaver and infused into a patient, restoring some insulin production.
However, two problems remain: lack of available islet cells from deceased donors and the limited lifespan of transplanted islet cells, leaving some patients to need repeated transplants. Creating islet cells from stem cells could solve both challenges.
As a research assistant professor at Mt. Sinai School of Medicine prior to joining City of Hope in June, Ku reported a promising strategy in the journal Diabetes to do just that. She cultured mouse embryonic stem cells with the right cocktail of factors so they became islet-like cells that express insulin. Similarly engineered human stem cells could potentially be used for transplantation.
And since the transplanted cells would contain stem cells, which undergo continuous cell division and perpetuate themselves, transplants based on stem cells might last longer. “You would want to select a population of cells that is self-renewing, so you can avoid repeated transplantation,” said Ku, who conducts her research in the Leslie and Susan Gonda (Goldschmied) Diabetes and Genetic Research Center.
At City of Hope, Ku will first adapt methods she developed for mouse embryonic stem cells to human cells. “That is not so easy,” said Ku, whose research is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases. “Human embryonic stem cells are pickier and take longer to complete the differentiation program than mouse cells.”
Ku also will look for stem cells capable of maturing, or differentiating, into islet cells in adults, similar to how neurobiologists searched for — and found — neural stem cells capable of generating new nerve cells in the adult brain. “If they did exist,” she said, “you would have a source of islet cells that would be better than embryonic stem cells.”