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Transplanted cells may hold the key to curing hemophilia A, Einstein scientists report
Date:2/14/2008

splantation, to make room for the donated cells to engraft and proliferate, the researchers gave recipient mice a dose of the toxic chemical monocrotaline to deplete their native liver endothelial cells.

Three months after transplantation, when we examined the livers of recipient mice, we found that the transplanted cells had engrafted and increased in number, says Dr. Antonia Follenzi, an instructor in pathology at Einstein and the lead author of the study. Even more important, those mice with the most transplanted cells in their livers produced factor VIII in sufficient amounts to completely correct their hemophilia A.

Efforts up until now to cure hemophiliaranging from faith healing by the Russian monk Rasputin early in the 20th century to clinical trials in the U.S. using gene therapyhave had limited or no success. While the Einstein study marks a significant advance against hemophilia A, Dr. Gupta cautions that more work is necessary before liver-cell transplants can be attempted on people. An important need, he says, is for safer alternatives to monocrotaline, the chemical we gave to recipient mice to create space for healthy donor liver cells. Fortunately, several drugs already in clinical use hold promise in that regard.

The principle established by this studyselectively injuring native endothelial cells and replacing them with healthy donor endothelial cellsmight also help in treating hemophilia B (the less common form of the disorder) and, more broadly, aid in tissue engineering in the many other areas of the body where endothelial cells are found, says Dr. Gupta. For example, he notes that endothelial cells isolated from blood vessels and transplanted into the heart could help in treating cardiovascular disease. In addition, he says that it may be possible to deliver therapeutic substances into the liver and other organs by combining gene therapy with the cell-transplantation approach used in this study.


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Contact: Karen Gardner
kgardner@aecom.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

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