Embryonic stem cells treated with growth factor reverse hemophilia in mice

CHAPEL HILL -- University of North Carolina at Chapel Hill researchers have made a discovery that may have implications for the treatment of liver-based genetic defects such as hemophilia A and B in humans.

Mouse embryonic stem cells treated in culture with a growth factor and then injected into the liver reverse a form of hemophilia in mice analogous to hemophilia B in humans, the new study shows. A report of the study appears in the journal Proceedings of the National Academy of Sciences today (Feb. 15).

The genetically altered mice lack the clotting substance factor IX, which in humans results in the hereditary bleeding disorder known as hemophilia B. This disease, much less common than hemophilia A, affects roughly one of every 35,000 people, primarily males.

Although embryonic stem, or ES, cells can differentiate into most cell types in the body, numerous problems have arisen in translating their potential into therapeutic strategies, the UNC School of Medicine study authors reported.

These problems include poor engraftment, limited function, rejection of engrafted cells by the immune system and teratomas, tumors involving a mixture of tissue not normally found at that site.

The new study used a line of mouse ES cells developed in the laboratory of senior co-author Dr. Oliver Smithies, Excellence professor of pathology and laboratory medicine at UNC.

A member of the National Academy of Sciences, Smithies has won many honors for gene targeting, a technique he pioneered. This technique allows for the development of mice with specific genetic mutations that mimic human illnesses such as hemophilia. In 2001, Smithies received the Albert Lasker Award for Basic Medical Research, often called "America's Nobel."

In the study, ES cells were treated with fibroblast growth factor for seven days prior to injection. As expected, this resulted in ES cells differentiating into early endoderm like precursors, which the researchers name

Contact: Leslie H. Lang
University of North Carolina School of Medicine

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