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Embryonic Stem Cells Treated With Growth Factor Reverse Hemophilia In Mice: UNC Researchers

"putative endoderm precursors," or PEPs. Endoderm refers to the inner layer of early embryonic cells that develops into the digestive and respiratory systems.

"Not only do ES cells differentiate into PEPs, they also engraft, persist, differentiate further and then function following injection, resulting in the persistent production of factor IX protein that can only come from a hepatocyte (liver cell) and hemophilia reversal," said study lead author Dr. Jeffrey H. Fair, associate professor of surgery and division chief of abdominal transplant surgery.

Moreover, he said, the PEP cells robustly engraft within the liver and were not recognized by the immune system as foreign.

"Within a few weeks, PEPs became hepatocytes," Fair added. "They went from something that is a very early grandparent of the hepatocyte to becoming hepatocytes. After 115 days, nearly four months after injection, mice still produced factor IX without immune suppression. This occurred even in mice that were a complete immunologic tissue mismatch to the PEPs. In addition, the incidence of teratomas was low."

The researchers believe this study demonstrates the power of multidisciplinary collaboration, said co-lead author Dr. Bruce A. Cairns, assistant professor of surgery and director of research in the N.C. Jaycee Burn Center. "This approach may not only be beneficial, but required in order to solve complex problems such as these in medicine."

Although a number of questions need to be answered, this work has great potential for future applications, not only as a novel therapeutic possibility for hemophilia but also for other genetic or acquired diseases of the liver, said senior co-author Dr. Jeffery A. Frelinger, Kenan professor and chairman of microbiology and immunology.

"The data published in this study shows that embryonic stem cells partially differentiated, are able to remain in the liver and be functional without apparent immunological rejectio
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Source:University Of North Carolina At Chapel Hill


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