Stanford scientists have published a report in which they tried to decrease the tumor propensity of embryonic stem cells. One of the chief characteristics of embryonic stem cells is that they like to grow--and grow, and grow, often leading to tumors. Previous research has shown that as few as two growing embryonic stem cells among millions of injected cells can lead to tumors, even if the cells are supposedly pre-differentiated.
In trying to get around the inherent danger of embryonic stem cells, the scientists developed an antibody against a previously unidentified antigen (stage-specific embryonic antigen-5, or SSEA-5) that is highly and specifically expressed on all human pluripotent stem cells--embryonic stem cells which require destruction of young human life, and induced pluripotent stem cells (iPS cells) that are produced by adding genes to normal skin cells, without the use of embryos, eggs, or cloning.
Their hope was that the antibody could be used to identify and separate the lethal tumor-causing cells from a population of embryonic stem cells. The anit-SSEA-5 bound to embryonic stem cells, as well as to the inner cell mass of early human embryos, the group of cells from which embryonic stem cell lines are derived after destruction of the embryo. Their next step was to try to use the antibody to remove tumor-forming cells from cultures of embryonic stem cells. According to senior author Micha Drukker:
"Commonly used differentiation protocols for embryonic stem and iPS cells often give rise to mixed cultures of cells. Because even a single undifferentiated cell harbors the ability to become a teratoma, we sought to develop a way to remove these cells before transplantation."
When the scientists injected human embryonic stem cells recognized by the anti-SSEA-5 antibody into mice, rapidly-growing tumors formed in 7 out of 7 mice injected. When they injected cells that were not recognized by the anti-SSEA-5 antibody, tumors formed in 3 of 11 mice injected. Combining the anti-SSEA-5 antibody with two other commercial antibodies decreased tumor growth, although they did see some smaller, less-diverse tumorous growths. The authors also only measured the incidence of tumors detected after the relatively short time of 912 weeks; longer periods of time would be required to see all tumors that arise from the embryonic stem cells.
First author Chad Tang noted that this was a "proof of concept" study, and that different combinations of antibodies may be required for embryonic stem cell cultures developing into different types of cells. It's also unlikely that the antibody technique would remove cells that had ceased growing and were supposedly differentiated, but resumed growth later. Certainly these results from a single small study will need to be confirmed with published data from other labs.
Stanford University has filed for patent protection for the use of these monoclonal antibody-based protocols to remove tumor-forming pluripotent stem cells from a cell mixture.
Two companies have begun experiments with patients, injecting embryonic stem cell derivatives into eyes and into spinal cords. It's far too early to tell whether any tumor problems may develop, though at least one of the companies has promised to follow patients for 15 years because of the tumor concerns inherent with embryonic stem cells. The fact that neither ACT nor Geron provided definitive published proof that they can control tumor formation is a significant concern, even among proponents of embryonic stem cells.