In the emerging field of regenerative medicine, some of the most promising developments revolve around so called "pluripotent cells" — cells like embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC) that can develop into just about any type of cell in your body.
Unfortunately, the differentiating potential that makes pluripotent cells like these so promising can also render them lethal. Now a team of research scientists has found a way to keep the potentially deadly side effects of stem cell therapy in check.
Pluripotent cells, when placed in the right environment, can be "told" by scientists to differentiate into any number of tissues. Why is this useful? Let's say a burn victim is in need of a skin graft, but the burn is so serious that he lacks the donor tissue necessary for such a procedure. Stem cells can be coaxed into developing into skin cells that can be transplanted to treat the victim's burns. But there is also an inherent risk to this procedure.
If any of the stem cells remain undifferentiated — i.e. any of the stem cells fail to develop into skin cells prior to transplantation — they can turn into dangerous tumors known as teratomas instead.
"Commonly used differentiation protocols for embryonic stem and iPS cells often give rise to mixed cultures of cells," said Dr. Micha Drukker, senior author of the research team's paper, published in this week's issue of Nature. "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."
Until recently, there was little that could be done to identify these undifferentiated stem cells prior to transplantation, but now Drukker's team of Stanford researchers has developed an antibody that is capable of doing just that.
As a cell differentiates, the landscape of its surface changes with it. When an embryonic stem cell develops into another cell type, for example, specific "landmarks" on its exterior will emerge, while other landmarks will cease to exist. By growing a number of antibodies targeted against undifferentiated stem cells, the researchers were able to identify not just which antibodies were the best at seeking out the undifferentiated stem cells, but which of the cells' "landmarks" the antibodies were actually being attracted to. The researchers called these stem cell—specific landmarks "pluripotency surface markers," or PSMs.
One of the antibodies produced allowed the researchers to identify a PSM that they named the "H type-1 glycan." The glycan was found on the majority of stem cells investigated, but only those that had yet to differentiate. The researchers named the antibody that was attracted to the glycan PSM "anti-stage-specific embryonic antigen 5," or anti-SSEA-5, for short.
While other PSMs and their corresponding antibodies were also identified, none were as effective at identifying undifferentiated stem cells as anti-SSEA-5. However, by targeting the stem cells with anti-SSEA-5 along with two other anti-PSMs, the researchers were able to completely separate the undifferentiated cells from the differentiated ones.
In other words, scientists would now appear to have the ability to not only identify but eliminate all non-differentiated (and therefore dangerous) stem cells from a batch of otherwise very useful cells. In doing so, they've overcome one of stem cell therapy's biggest hurdles, and paved the way for the future implementation of groundbreaking stem cell treatments.