STAP cell deja vu? 28 VSEL papers flagged by Bik

The stem cell field has puzzled on and off for years over a constellation of papers on purported stem cells including so-called VSEL and MUSE cells. Many of us haven’t been convinced that these are real stem cells. I see VSEL and MUSE fitting into a larger pattern of dubious stem cell claims including the STAP cell debacle.

Now the whole idea of VSEL, which stands for very small embryonic-like stem cells, has taken a big and perhaps final blow. The primary VSEL proponents, the University of Louisville team of Dr. Mariusz Ratajczak, have just had more than two dozen papers flagged by Dr. Elisabeth Bik for various irregularities. Dr. Bik is arguably the top scientist in the biomedical sphere at identifying problems with research papers.

VSEL & MUSE cell puzzles

What are VSELs supposed to be?

The proponents of both VSEL and MUSE cells claim in each case that these are adult stem cells that have unusual properties including potency (the ability to make a variety of differentiated cells) far beyond that of typical adult stem cells.

For me as a cell biologist, many things about VSEL didn’t add up and still don’t. As far back as seven years ago I posted in a skeptical way about VSELs.I wondered whether they might be akin to Sasquatches (aka Big Foot, Yetis, etc.)

Much of my skepticism initially came from the radical notion that us adults would have such potent, perhaps even pluripotent, stem cells in our bodies.

Wouldn’t that pose a great risk of teratoma, the unique tumor that can be spawned by pluripotent cells, or cause other problems?

Later, when STAP cells first came onto the scene with those two Nature papers, I felt certain reverberations between some of the STAP cell paper claims and those we sometimes heard about MUSE and VSELs. STAP cells supposedly were the pluripotent product of reprogramming adult non-stem cells using stress such as low pH, but the whole thing turned out to be fake.

So what’s going on now with VSELs and what’s their history?

VSEL already debunked?

While STAP cells were relatively quickly debunked and that was by a collective global effort aided right here on The Niche, in contrast VSEL and MUSE cell research continued on despite in my view there being little evidence VSEL are real.

Even to this day to my knowledge only a small handful of labs claim to be able to readily isolate and study VSEL based on the published protocols. This kind of situation makes it harder for the community to be sure what the real deal is with these purported stem cells and it certainly raises doubts.

Some of you may remember that stem cell pioneer Irv Weissman published a VSEL refutation of a sort in Stem Cell Reports back in 2013. Their paper was the main impetus for my “Sasquatch” post here on The Niche about VSELs that same year that I linked to earlier in today’s post.

To me the Weissman paper essentially sealed the issue, but even so VSEL papers, grants, and even biotech investments (e.g. by a firm formerly called Neostem) continued popping up.

Notably, these kinds of supposed “special” adult stem cells have drawn the attention and support of the Vatican including big funding. If VSEL could truly act like human ES cells then for religious reasons that would make them more appealing in some sectors.

Bik flags more than 2 dozen Ratajczak team papers

Now, Dr. Bik has flagged a slew of papers of the team of the primary VSEL proponent Mariusz Ratajczak for irregularities.

She notes what look to be instances of data reuse in separate independent papers by this team without the authors seeming to note the reuse. There are also instances of text reuse in some papers.

Potentially most troubling, some figure images from Ratajczak team papers have some very puzzling elements.

For example, take a look at the composite picture above of annotated images from figures of 2 different Ratajczak team papers, including on the left what may be the very first VSEL paper, published in 2006. The figure panels from the 2 different papers seem to have the same cell in them, but rotated and/or with the background looking different. Follow the black arrows and see what you think. Same cell?

In addition, look at the surrounding context for that cell in the 2006 paper image on the left (the red rectangle above it). It has another cell right above it but in the image of what seems to likely be the same cell image over in the 2007/2008 paper, the roughly equivalent area is generally blank (see its associated red rectangle). Isn’t that odd?

Returning just to the image from the 2006 Leukemia paper, there seem to be 2 versions of another single cell (see black boxes) just in Fig. 1b. Compare the image material in the 2 black rectangles. Same cell?

However,  if you look more closely at these 2 possible “twin” cells specifically where I have pointed the blue arrows, you can see that the cells do have some differences like a cellular protrusion in one case but not the other. What’s the deal with that?

I also again recommend checking out Dr. Bik’s post as well for instances of other seeming irregularities. The number of potential issues or pubs involved could grow as well since Dr. Bik has raised these red flags on PubPeer here, drawing more attention to them.

End of the VSEL line?

I see what Bik has identified as a big hit to the rigor of the overall VSEL literature.

Is this the final nail in the coffin for the whole idea of VSELs or will they live on? I wouldn’t be surprised if we continue to see more VSEL papers in 2021 and on, but I hope not. In my view this kind of stuff is harmful to the stem cell field.