Rui Dai: Our Misunderstanding of Stem Cells

It’s always troubling to see a misunderstanding concerning a recent scientific discovery. The latest concerns an Israeli team of scientists, led by Lior Gepstein, that converted skin cells from two patients with heart attack into stem cells and then heart cells.

SourceFed, one of my favorite channels on YouTube, proclaimed that Gepstein’s study means that a cure for heart disease is “10, 15 years out.” Similar statements were also circulated by The Guardian, The Los Angeles Times, CBS News, and others.

However, the claims that SourceFed and other news outlets have made are not true. If anything, the field of heart regeneration is moving away from what the study did. If there is a cure for heart attack in 10 to 15 years, it will not be because of this study.

Generating stem cells from skin cells is relatively old news. This feat was first performed in 2006 for mice (2007 for humans) concurrently by two teams of scientists led by Shinya Yamanaka in Japan and James Thomson in the United States, respectively. Since then, the technology has evolved so fast that generating heart cells from stem cells is truly nothing new.

Stem cells often differentiate into heart cells, or cardiomyocytes, without much technical intervention. Even I, a mere undergraduate student, have generated beating heart cells several times without much trouble, from mice and rat skin cells. And I’m not even in the field of heart regeneration. I work with stem cells in neurobiology.

The technique to generate heart cells from skin-derived stem cells (or induced pluripotent stem cells) has existed for a long time. After a brief search on Google Scholar, I found a paper published in 2008 detailing how to generate heart cells from skin cells. This may not seem like a long time ago, but in the stem-cell world, that’s almost an eon.

So if we have been able to generate heart cells for such a long time, why has no one actually successfully transplanted heart cells into patients? One of the reasons is that there are so many different problems with not only transplanting heart cells onto a beating heart but also with the induced pluripotent stem cells that are derived from skin cells.

When a heart is damaged, scar tissues grow over the damaged part of the heart. The scar tissue does not function like regular heart cells. Instead of beating, the scar tissue just sits there, not doing anything and getting in the way of the beating heart. It’s just like a scab on your arm from a scrape. The only difference is that the scab eventually comes off, because your skin is constantly making new cells, but the scar on your heart doesn’t, because heart cells rarely regenerate, if at all.

Transplanting new heart cells without removing the scars is like putting a new layer of skin over the old scab and expecting the scab to go away. The old scab doesn’t go away. More likely, the transplanted tissue will just die off.

As a result, instead of trying to transplant new tissue, the field of heart regeneration is now trying to transform the cells in scar tissue into beating heart cells. Though there are also problems with this new direction, it opens up ways of solving a whole host of other problems that plague heart-cell transplantation.

Lior Gepstein, the leader of the newly published heart-cell transplantation paper, claims that the newly generated heart cells are “healthy and young — the equivalent to the stage his heart cells were in when [the patient] was just born.” Though Gepstein is not exactly wrong, he isn’t completely right, either. The problem is more complex.

Generating stem cells from skin cells has a whole separate set of problems. Contrary to what Gepstein claims, the newly generated stem cells from skin cells aren’t exactly the same as the patients’ cells and will most likely be rejected if ever transplanted.

It was thought, and I think Gepstein uses this logic, that if the cells are derived from a patient’s own cells, then the body won’t reject them. However, a study published last year by a team in University California San Diego suggests otherwise. The team injected stem cells derived from mouse skin cells into mice with identical genetic makeup. Most studies transplant cells into mice that have little to no immune system. This way, the cells can never be rejected. However, the study from UCSD transplanted the cells into mice that have a normal immune system. Surprisingly, within a month, there were barely any trace of the stem cells, or of any other cells that they could have generated. The mice’s immune system had rejected the induced pluripotent stem cells.

In this sense, induced pluripotent stem cells are not perfect. Your body can still reject them even if they came from your body. Note, however, that this one study does not condemn the entire induced-pluripotent-stem-cell field either. It does not mean that induced pluripotent stem cells will definitely be rejected if ever transplanted. It only indicates that there is a lot more complexity. Much more research needs to be done before anything can be concluded.

I love stem-cell science. That is what I plan to work on for my future career. However, our current understanding of stem cells is leading the public down the wrong path. The future cure for heart disease will not be found in 10 to 15 years by transplanting heart cells developed from skin cells.

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