Gene discovery limits tumor risk for stem cell therapy

Hebrew University researchers analyzed the genetic basis of tumor formation and identified a key gene involved in this unique tumorigenicity.

By JUDY SIEGEL-ITZKOVICH
fetus 88 (photo credit: )
fetus 88
(photo credit: )
A method to potentially eliminate the tumor-risk factor when using human embryonic stem cells (hESCs) - developed by researchers at the Hebrew University of Jerusalem - has paved the way for further progress in stem cell therapy. These stem cells, taken from human embryos not used for in-vitro fertilization, are theoretically capable of differentiation into all types of cells, and are thus defined as "pluripotent." This ability, along with remaining undifferentiated indefinitely in culture, make regenerative medicine using hESCs a potentially unprecedented tool for the treatment of various diseases, including diabetes, Parkinson's disease and heart failure. A major drawback to the use of stem cells, however, remains the demonstrated tendency of such cells to grow into a specific kind of tumor called teratoma when they are implanted in laboratory mice. It is assumed that this tumorigenic feature will occur when they are transplanted into humans as well. The development of tumors from embryonic stem cells is especially puzzling, given that these cells start out completely normal. A team of researchers at the stem cell unit in the Hebrew University's Silberman Institute of Life Sciences genetics department have been working on various approaches to deal with this problem. The researchers are headed by Prof. Nissim Benvenisty and doctoral student Barak Blum. In their latest project, the researchers analyzed the genetic basis of tumor formation from hESCs and identified a key gene involved in this unique tumorigenicity. This gene, called survivin, is expressed in most cancers and in early-stage embryos, but is almost completely absent from mature tissues. The survivin gene is very highly expressed in undifferentiated hESCs and in their derived tumors. By neutralizing the activity of survivin in the undifferentiated cells and the tumors, the researchers were able to initiate programmed cell death (apoptosis) in those cells. The inhibition of this gene just before or after transplantation of the cells could minimize the chances of tumor formation, but the researchers caution that a combination of strategies may be needed to address the safety concerns regarding tumor formation by human embryonic stem cells. A report on this latest HU project appeared in the online edition of Nature Biotechnology. Others working on the project are Ph.D. student Ori Bar-Nur and laboratory technician Tamar Golan-Lev.