Thursday, September 12, 2013

Creating embryonic-like stem cells in living mice a path to therapies? Not so fast

Flickr image: Rick eh?
The news cycle for the past day has been filled with articles about work in Spain in which the researchers reprogrammed adult cells in a living mouse to become like embryonic stem cells, and in some cases, even more primitive cells.

A few of the articles covering the work captured what the researchers actually showed. But far too many articles suggested that the work represented a breakthrough close to making a difference in the clinic.

One of the worst was the consumer web site Medical Daily, which wrote this headline: “Embryonic Stem Cells Produced Inside A Living Organism, Paving Way For Regenerative Medicine Within Your Own Body”. This work is a cross-country interstate away from “paving” a way for regenerative medicine in our bodies. There are several reasons:
  • No one wants embryonic-like stem cells in their body. They form tumors. In fact, it was the presence of tumors in the mice that told scientist they had succeeded in their goal. Scientists who are working with embryonic stem cells to create new therapies first turn those stem cells into a state where they don't form tumors before attempting to transplant them.
  • The mice the scientists used in the study were completely artificial and cannot be re-created in humans. The group started with mice that were genetically engineered to express the four genes classically used to reprogram adult cells into iPS stem cells in a lab dish. Only when the scientists prodded those artificially added genes to turn on did the cells reprogrammed into the embryonic-like state. 
  • In humans you would need to stop the reprogramming process at an intermediate state so that you don't create the tumor forming embryonic-like cells. This intermediate state progenitor cell would be safer but still able to form several types of cells. Figuring out how to do that and then how to mature those into the desired type of tissue, say heart muscle, is a huge-beyond-belief undertaking. However, the research team does write that this is their next challenge.
Eryn Brown wrote one of the most balanced stories in the Los Angeles Times. In it she quotes Andrew McMahon who holds a CIRM Research Leadership grant and directs the Broad Center for Regenerative Medicine and Stem Cell Research at the University of Southern California. McMahon says he was somewhat puzzled by the work and unsure what question the scientists hoped to answer.
“It was a way to survey and see if anything interesting would crop up.”
The work does raise the possibility of some interesting work down the road to advance the science of growing iPS cells in the lab. The reprogramming factors seemed to be more efficient when turned on in a live animal than when turned on in cells in a lab dish. If researchers can figure out why, the field of creating iPS cells could move more quickly. Also, the reprogramming went further back to a more primitive state in some cases. Embryonic stem cells cannot form the tissues need to create a placenta that would be needed for a functional embryo, but some of these new cells could. That is a big “why” calling out.

So, in the short term, in the best case this work is a tool that points to some potentially valuable follow-up research. But it could also turn out to be not much more than a laboratory novelty.

Don Gibbons

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