Stem Cells, Stressed Cells, Healing, and the Lure of Rejuvenation

A recent study in Nature, entitled “Stimulus-triggered fate conversion of somatic cells into pluripotency“, suggests that subjecting cells to dangerous but non-lethal conditions (such as a bath in acid, or a mechanical squeeze) can turn them into stem cells. Unsurprisingly, this publication set off a bit of a media blitz, and then it turned out that there were numerous problems with the data. As a result, the paper is now being ‘investigated‘. It might all be fluff. It might still be real. It almost certainly isn’t as exciting as it was initially presented. Whatever ends up being the truth of the science, however, it will have been a fascinating example of how science deals with — or doesn’t deal with — topics that aren’t simply interesting due to their scientific merit.

A Fountain of Youth in a Cell Culture Hood

Stem cells capture our interest more because of their philosophical ramifications than their actual medical value. Part of that is that their potential value (as measured by the medical technologies they could facilitate in the future) far outstrips their actual value (as measured by what we can do with them today). And part of that is because it’s just a really good story. Cells that can turn into anything and everything, rebuilding our bodies and unmasking the potential we had when we were still young and healthy and healed easily.

Induced pluripotent stem cells — iPS cells — have even more metaphorical bang for the buck. Certainly, they are a more promising technology in certain ways: more readily available and less ethically fraught because we can derive them from tissue samples freely given by an informed adult without any hint of ‘potential fetal lives’; less likely to be rejected by the host they are implanted into because they are that host’s native cells. Moreover, they are, as literally as possible, cells in which the clock of aging has been wound back: adult cells which have been thrown back into a childish state. When we talk about iPS cells, when we talk about “how to turn a cell into a stem cell”, we are talking about a chemical, molecular fountain of youth in a very literal way.

That Which Does Not Kill You

I think it’s that metaphorical significance, and that metaphorical resonance, that really made this paper take off the way it did. Because we have a saying for it already: that which does not kill us makes us stronger. In this case, chemical and physical changes that hurt a cell but don’t kill it will instead give it super powers — turn it into an iPS cell.

Really, we might as well be setting radioactive spiders on our culture dishes, for all that this story fits with our zeitgeist.

But there’s an obvious reason why this HAS to be very rare in nature, or of limited benefit, at least in human cells. And that’s because the phrase “That which does not kill you makes you stronger”, while it might have a good deal of emotional resonance with many of us, isn’t literally true. We do not come back from injuries stronger than before; more often we are barely able to get back to our starting point. Life is a continual process of gaining scars and making accommodations for our injuries. And if you crush your leg beneath a falling wall, you’re going to lose the leg, not get a bunch of stem cells and regrow the muscle so it’s better than it ever was.

After all, what causes pH changes in your blood, or mechanical stress on your cells, more than an injury?

Healing and Regenerating

There are absolutely organisms which, when faced with a wound response (something like a rapid pH change or a mechanical stress) DO make lots of stem cells, and DO regrow. Probably the best examples of these are planarians, which can regrow from something as small as 1/32 of their original body size. They are fascinating, and a huge amount of interesting research into how to heal people from wounds and diseases is taking place, using planarians and other regenerating-animals as model systems.

And that’s the final part of why this paper was so interesting, and so tempting, and is causing so much doubt. Because we know that human cells don’t work that way. We know that those pathways, in fact, have been inactivated in mammalian wound response — and that disabling a certain gene in mice means they can regenerate their hearts after a heart attack, for example.

Is it possible that this does happen, but at a rate that is low enough or situations that are specific enough that they do not meaningfully contribute to wound responses? Yes. Is it likely that bathing cells in acid is going to be the next big way to generate new livers for transplant patients? No.

But man, wound that be a good story.