Embryonic Stem Cell Cancer Issue Remains Unresolved

Scientists have been working on this for nearly a decade now on making ES cells capable of being used directly in therapies. They have been stymied by three primary problems; the potential for tissue rejection (which we will not get into in this post), the cells’ propensity to form tumors called teratomas, and the problem of some ES cells appearing to be pre cancerous, making them very risky to inject into a living patient. With regard to the latter issue, it turns out that the healthiest appearing ES cells may be the most dangerous. From a blog entry over at Nature:

Are ruddy cheeks a sign of health or a symptom of sickness? New work from Mickie Bhatia and colleagues at McMaster University suggests that, when it comes to embryonic stem cells, the very qualities researchers use to pick out a robust cell line may in fact be bestowed by precancerous transformations. “Current measurements are not capable of distinguishing the difference between great stem cells and cancer stem cells in vitro,” says Bhatia.

The problem, apparently, is that abnormalities are submicroscopic and can’t be determined before they transform into specific body tissues (differentiation). This could mean that the potential cancer threat—which is in addition to the teratoma tumor issue—may be very hard to solve:

“This paper shows that human ES lines with submicroscopic genetic abnormalities can display altered growth and differentiation properties suggestive of premalignant change,” says Martin Pera who studies embryonic stem cells at the University of Southern California in Los Angeles. “In other words, a normal karyotype is not necessarily a guarantee of a normal genetic makeup within a cell line.”...One of the “major challenges to the field” is developing techniques that can detect rare, abnormal cells, particularly if the transformations are not due to changes in gene sequence.

Also important, he says, is figuring out just how and when such cells might be dangerous. “Ultimately it may be difficult or impossible to rule out with certainty that a given culture is totally free of abnormal cells.”

If that is true, these cells may never be able to meet the potential scientists held out for therapies (which is to be distinguished from bench science use).

Note, this has nothing to do with the Bush policy or using older stem cell lines. It may be a consequence taking these cells out of their sphere of natural development in the living embryo.

What of the alternatives to ESCR? So far, IPSCs also have a teratoma problem—which is one of the signs of pluripotency—and a potential cancer problem caused by using viruses to affect the changes, although the virus issue appears well on its way to being solved. Umbilical cord blood stem cells can be tissue typed more readily than bone marrow and so far as I have seen, have no tumor issues. Adult stem cells do not exhibit tissue rejection (since they are the patient’s own cells), tumor formation, or cancer, and are in many early human trials for a variety of ailments, as we have often discussed here.