Stem Cell Surprises

An unwanted immune response to induced pluripotent stem cells (iPSCs), reported in Nature,1 is being touted by LiveScience as near-utter failure for iPSCs.

Early stem cell research involved adult stem cells (ASC) and embryonic stem cells (ESC). But the 1995 Dickey-Wicker Amendment banned federal funding for research that destroys human embryos. (President Obama and NIH director Dr. Francis Collins2 wish to allow embryos already doomed to destruction to be experimented on with the government’s monetary blessing.)

Unlike ASCs harvested from the patient himself, ESCs tend to provoke immune rejections. ESCs also tend to produce cancers.

The popularity of ESCs has hinged on their potential to transform into any sort of needed cell. But unlike ASCs harvested from the patient himself, ESCs tend to provoke immune rejections. ESCs also tend to produce cancers. ESC clinical trials have been disappointing. ASCs, on the other hand, have already provided safe, effective medical treatments.

The 2007 discovery that ASCs could be reprogrammed to an embryonic-like state suggested new possibilities for stem cell research. It has been hoped that these induced pluripotent stem cells (iPSCs) could do all the things everyone hoped ESCs could do without destroying tiny human lives. As a bonus, if these iPSCs were harvested from the patient himself, they should not provoke immunologic rejection.

Dr. Yang Xu’s team tested the immune response of mice to ESCs and to iPSCs. Because ESCs tend to produce teratoma tumors in mice, the researchers knew that a mouse which did not develop a teratoma was having an undesirable immune response. (This appears a little backwards, but they’re testing for an immune reaction, not treating an illness. The test itself—an excellent way to test the immunogenicity of the stem cells—is a stark reminder that ESCs have a nasty habit of causing tumors!)

Unexpectedly, the mice did not reject the ESCs but did reject the iPSCs. The LiveScience writer uses emotionally charged language, saying the mice “violently rejected” the iPSCs but accepted the ESCs “with ease.” To paint a graphic picture, the mice which rejected iPSCs showed it by “violently” not getting tumors. The mice that accepted the ESCs did so by developing tumors “with ease.”

The LiveScience writer brands the test a failure for iPSCs. He makes his bias plain, stating “the intent of this conservative Christian-based law was to stop all research on human embryos — or more precisely, on a blastocyst, a collection of a few dozen undifferentiated cells — because a considerable percentage of Americans consider this human life with a soul.” He goes on to say, “Science, however, tells a different story, one in which humans evolved over the course millions of years [sic], with no clear distinction between the last ape ancestor and the first human with a soul.”3

Human beings are created in the image of God, distinctly different from animals. Therefore, we seek to protect unborn human beings.

LiveScience says, “From a scientific perspective, embryos bring the potential of life — whether that life is among the approximately 150 million babies born each year, or among the approximately 25 percent of all fertilized eggs lost in a natural miscarriage, or among the countless blastocysts thrown away daily at fertility clinics, or among the millions of patients who someday could be cured through stem cell research.” Thus the writer ignores the value of Dr. Xu’s findings, apparently to gain support for ESC funding, implying that since lots of embryos die on their own, killing them is no big deal.

Dr. Xu’s results do not doom iPSCs. First of all, there is more than one way to prepare iPSCs—Dr. Xu’s lab tried two ways and got varying results. No doubt more methods will be discovered. Furthermore, as Dr. Xu says, “Our immune response assay [the mouse-teratoma test] is a robust method for checking the immune tolerance, and therefore, the safety of iPSC that may be developed.”4 He adds, “This result doesn't suggest that iPSCs cannot be used clinically.” He believes only certain types of iPSCs will provoke immune rejection. In other words, Dr. Xu found out what didn’t work. And he developed a good test for stem cell safety.

Thomas Edison reportedly discovered 700 ways not to make a light bulb before finding one that worked. So let’s avoid dashing all hopes of iPSC’s potential just because we found out that they behave very much like the ESCs they are supposed to imitate.