September 28, 2020

The Niche

Knoepfler lab stem cell blog

Transdifferentiation does not make iPS cells obsolete

Do we still need iPS cells if transdifferentiation is so cool?

Wait, how did we get to the point that people are asking me that extreme question?

When iPS cells were first introduced to the world by Shinya Yamanaka, who I think will win the Nobel Prize sometime in the next few years, some folks went off the deep end. For example, opponents of human embryonic stem cell research (hESC) pronounced the need for hESC to be gone.

Others like Dr. Oz, to put it lightly, did not understand the nuances of the stem cell field and made gross misstatements. Oz had his train wreck of an appearance on Oprah saying so wrongly “the stem cell debate is over” with hero Michael J. Fox present. It is painful to even think about that stupid stunt by Oz so I’m not even going to link to the video.

A half a dozen years later, we still need hESC even though iPS cells are a quite powerful technology.

Now some are questioning whether we even need iPS cells if transdifferentiation is so powerful.

These folks ask “why not eliminate the middle man (i.e. iPS cells) if we can directly make the differentiated cells we want from cells like fibroblasts?”

I’m hearing this question more in the last week what with a new, very neat paper in PNAS from Marius Wernig on transdifferentiating fibroblasts into neural progenitors.

Previously Wernig’s team had made neurons from fibroblasts. What makes this new paper quite interesting is that neural progenitors are likely to be far more useful for regenerative medicine than actual neurons because neurons made in a dish are unlikely to transplant and engraft well.

My colleague Amy Adams from CIRM has a nice piece on Wernig’s work on the CIRM Research Blog.

Transdifferentiation is without a doubt a very powerful approach to exploit in the future to make clinically relevant stem cell-based drugs for regenerative medicine. However, it is very new (making even iPS cells seem like a mature technology) and there are very few publications on it.

My own lab toyed with it a few years back with some interesting, but unpublished results.

The reason why I think transdifferentiation has not been published more is that it is a very tricky, inefficient technology right now. It is very possible that this will change, but it is still early days. For this reason alone, I think iPS cells are here to stay for a long time.

In addition, we also do not know how cells made from iPS cells and transdifferentiated cells really stack up head-to-head in a clinically relevant setting. iPS cell derivatives could prove superior. The jury is out.

So for now, we need hESC and iPS cells as we continue to learn more about transdifferentiation, a very exciting new technology. It is also important to point out that transdifferentiation was only something people tried after being inspired and instructed by Yamanaka’s iPS experiments!

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