November 25, 2020

The Niche

Knoepfler lab stem cell blog

Ian Wilmut, Dolly’s dad, says dump hESC? What does this mean?

Sometimes a top scientist makes news with a quote on research and that happened with Ian Wilmut recently on stem cells.

Ian Wilmut
Professor Ian Wilmut.

Move away from research on human ES cells (hESC) in favor of very new and still largely unclear trans-differentiation technology?

I say, no way.

But, Bradley Fikes of the North County Times has reported that Ian Wilmut, who cloned the first mammal Dolly the sheep, argued for a shift from ES cell research and toward trans-differentiation at the Stem Cell Meeting on the Mesa in La Jolla, CA.

Reportedly, Wilmut expressed his enthusiasm for trans-differentiation and said it was preferable to ES cell research. He is quoted as saying the government will be very unlikely to fund ES cell research if trans-differentiation becomes more common. That is a big “if” and one that may not come to reality any time soon.

Trans-differentiation is a remarkably exciting, emerging technology, but it remains relatively unstudied…or at least there are relatively few published studies most likely because transdifferentiation is an extremely difficult feat to achieve.

I myself predicted at the beginning of 2011 in my post on stem cell predictions for 2011 the following:

Transdifferentiation competes with iPS cells in terms of translational promise. Quite a few more transdifferentiation papers are published and transdifferentiated cells are found to be conclusively safer than differentiated iPS cells. More safety concerns about iPS cells are raised too. This all raises the question of whether transdifferentiation is a better approach for the clinic than using differentiated iPS cells, but transdifferentiation may not work for some cell types giving iPS cells a possible advantage. ES cells continue to be the gold standard.

However, my prediction was sadly far too optimistic.

There has not been much of any progress on transdifferentiation this year and I do not believe it is for lack of people trying. From what I hear, transdifferentiation is far less efficient “in the field” than iPS cell formation for example. I was right though that ES cells would continue in 2011 to be the gold standard and I predict that hES cells will remain the gold standard in 2012 as well.

Thus, it is surprising that Wilmut (assuming he was quoted accurately) would have been so quick to dismiss ES cells when trans-differentiation is so new and challenging with only a couple studies. Perhaps, as we hope, transdifferentiation will indeed prove the best, safest method for cell therapies, but I believe that reality is not as close as we had hoped. In the mean time, why abandon ES cell research? With all respect to Wilmut, I think this would be counterproductive.

It is also important to note that Fikes’ article contains an as yet uncorrected error saying that Geron was the only company with hESC in clinical trials, when in fact Advanced Cell Technology has not one, but two hESC-based combined PhaseI/II clinical trials underway and that so far have produced no negative outcomes.

I was unable to attend the mesa stem cell meeting due to conflicts so I can’t say first hand what Ian Wilmut said, but I believe that hESC still remain the most advanced pluripotent stem cell with potential for therapies. The NIH continues to fund substantial hESC research and there is not sign of a decrease in interest.

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