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Tumors caused by pluripotent stem cells can be tackled with radiation, say Stanford researchers

In the pantheon of weird human tumors, a teratoma has to take the cake. Typically arising from relatively unspecialized cells, these tumors are a Frankenstein's monster amalgamation of tissues that can include hair, teeth and bone. They can be the butt of jokes by weary cancer biology graduate students (and even some extremely adventurous knitting projects), but in reality they are no laughing matter. In particular, they are a very real concern for scientists and physicians working to bring stem cell therapies to the clinic. In some cases, injecting stem cells into an animal or human can form, you guessed it, a teratoma.

Recently several scientific and newspaper reports have detailed the formation of tumors in so-called "stem cell tourists" who have traveled out of the country to receive putative stem cell therapies unapproved for use in the United States. (To learn more about this phenomena, and what experts think of it, check out my 2011 article in Stanford Medicine magazine.) More recently, we reported that three women who participated in an unproven, experimental therapy in Florida touted as a clinical trial were blinded when stem cells from fat were injected into their eyes.

Now cardiologists Joseph Wu, MD, PhD, Patricia Nguyen, MD, and medical student Andrew Lee, PhD, have found that, at least in mice, it's possible to halt or reverse the growth of human teratoma cells arising from the injection of pluripotent stem cells with radiation. This is a surprise because naturally occurring teratomas are relatively resistant to the treatment.

They've recently published their results in Stem Cells.  I spoke to the trio to learn more about what their research might mean to future human stem cell therapies.

As Nguyen explained:

As clinicians, our goal is to inject differentiated cells obtained from stem cells to repair damage, however it is very difficult to ensure a cell product that is 100 percent pure. So at very high donor cell numbers there may be residual undifferentiated cells, and thus a risk of teratoma formation. We found that, although naturally occurring teratomas are resistant to radiation treatment, those formed in laboratory mice from undifferentiated stem cells shrunk dramatically after radiation exposure. We also didn't see any significant damage to surrounding tissue.

Lee continued:

When we isolated cells from the irradiated tumors and reinjected them into mice, we found that it took far more cells — three orders of magnitude greater — to cause teratomas in the new animals, even though they are in the same microenvironment as they were in the original animals. This is the first time that this treatment, known as external beam radiation therapy, which is the standard-of-care for many solid tumors in humans, has been shown to be effective against tumors formed by pluripotent stem cells.

The researchers believe that the pluripotent-stem-cell-derived tumors are more sensitive to radiation than naturally occurring teratomas because they have a higher proportion of undifferentiated, rapidly dividing cells. Zapping these types of tumors with radiation could possibly be an effective way to combat those that occur in anatomically sensitive areas such as the eye, brain or spine, the researchers believe. It might circumvent the previously suggested strategy of including a genetic "kill switch" in the transplanted cells to be activated if tumor formation is observed. Although this approach has promise, it may be more difficult to obtain Food and Drug Administration approval for the use of these types of genetically modified cells in humans.

Wu summarized:

We've been working with induced pluripotent stem cells for over ten years now. The primary questions have always been: A) What type of immune response might await these cells after transplantation? and B) Are these cells going to form tumors? Last year we published a report showing a combination of MRI technology and serum biomarkers offers the highest sensitivity for detecting very small stem-cell-derived teratomas in mice. Now, we're learning it might be possible to slow or eradicate the growth of these tumors with the use of external beam radiation. This could be an important treatment strategy for victims of stem-cell tourism, and may reassure physicians and regulatory agencies working to bring stem cell-based therapies into the clinic.

Previously: A stem cell "kill switch" may make therapies safer, say Stanford researchers, A good 'coach' and the right environment keeps stem cells in check, say Stanford researchers and "One of the most promising minds of his generation": Joseph Wu takes stem cells to heart
Image by Pixabay

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