VSEL controversy: Ratajczak’s response to criticism

by Alexey Bersenev on September 21, 2013 · 2 comments

in consensus, other adult stem cells

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We’re tightly following the controversies surrounding VSEL cells. As you know, the recent series of papers put under question of VSEL cell existence and highlights the problems with reproducibility. We were waiting for response of Mariusz Ratajczak – a man, who discovered VSEL. But so far he commented only in mass media:

“Why didn’t Dr. Weissman’s people contact us three or four months ago when they were having trouble?” Ratajczak said. “And now he wants to collaborate?” And then in a less frustrated tone of voice: “Okay, he can come and see me any time.”

“We are right and you will see,” Ratajczak says. “The truth will prevail.”

Last week, we finally got a detailed report from Ratajczak’s group, which attempts to address every challenging comment from critics. Because you can freely download this report and read it, I’m not going all over it today. I’d encourage you to evaluate it and comment under this post!

Few things I’d like to mention here. First, emotional aspect of debate:

Interestingly we were recently confronted with a rather unprecedented brouhaha/bone of contention against very small embryonic/epiblast stem cells (VSELs).

Scientific writers fuelled this attack by mediating their personal views through highly respected journals [25,26]. Among their attacks and arguments we found many errors and a huge amount of inaccuracy. In support of their written text comments were recruited from a rather narrow group of investigators. In truth these investigators, we’re afraid, allegedly had vested financial interests in iPSCs and ESCs technology. In brief the small nucleus of attacking scientists declared that VSELs, like other stem cells isolated from adult tissues have no future in regenerative medicine, and in fact are artifacts. What is perverse in our minds is the claim that clinical trials based on VSELs were a fake, or at least were not justified. We cannot help thinking that this was a competitors vicious attack on a grant allotted to investigators working on VSELs through a peer-review system, by National Institute of Health and Department of Defense in USA.

I understand what scientist can feel after all this criticism, but, I think, it could be wise to not use such language in scientific journal. I don’t think all groups, which were not able to reproduce VSEL, have “vested financial interests in iPSCs and ESCs technology”. I myself have no any financial interest, but I think, clinical trials are not justified.

Ratajczak then comments on ties VSEL and Vatican:

The unprecedented furor that has been generated around this topic makes one wonder what is really going on? We are approaching delusion: think the recent VSELs stories also raised questions about whether the Vatican is using VSELs to try to control science [25,26]. In fact, yes, some of us are Catholic like many others and yes we have started this research through curiosity but I am not a scoundrel as some would like to portray me. I am a firm believer in science and I shall try once again to gather all the facts in our possession to bring to this editorial crucial evidence about the existence of VSELs.

The “furor” in mass media started after publication from Irv Weissman’s group. We should appreciate the fact that Weissman has a lot of authority and respect in stem cell research field. Well, taking in account commercialization (NeoStem), religion (Vatican), launched clinical trials, this “furor” was expected. Also, I’d like to point out that, unfortunately, scientists love to play “authority games” like in kinder garden. Instead of collaboration and resolving controversies, they like to poke each other. To me it looks very childish.

This editorial addresses a lot critical points with an emphasis on Weissman’s study. Because VSEL isolation totally rely on flow cytometry, significant part of report dedicated to gating strategies and FACS staining.

vsel_loss

I was glad to see the following:

We plan to highlight these methodological aspects in more detail in a separate paper focusing exclusively on flow cytometric pitfalls and techniques in rare stem cell characterization, including for VSELs.

It will be great if each group can publicly share flow cytometry files (for example on Cytobank) and everyone can play with back gating.

Because of the biggest impact of Weissman’s paper, this response is mainly focused on it. Very few comments about Alt’s and Dulak’s studies. Nothing about Madrigal’s study. The issue with pluripotency markers was not addressed. Admitting a lack of human VSEL characterization:

On the other hand, we have always emphasized that, in contrast to their murine counterparts, much work still needs to be done to better characterize human VSELs.

Ratajczak pretty much stopped to call VSEL “pluripotent stem cells”. In this editorial he called VSEL “multipotent cells”, but with emphasis:

…possess several in vitro features expected from pluripotential stem cells.

Finally, the authors wrote to “deniers”:

we frankly wonder why, faced with the difficulties of characterizing VSELs by a handful of other groups [27-29] these groups have not openly, as is usual in science, requested our help. You (scientists) are wholeheartedly welcome to address yourselves to us.

The truth is that it’s not usual in science. Many labs would not contact lab-originator and ask why they were not able to reproduce a protocol. And now it’s late. Would you imagine Weissman and Ratajczak now are calling each other, exchanging kind comments, setting up collaborations and sending people over to learn? I can’t imagine it. They are in the war right now.

I’d like to encourage you to read this editorial carefully and evaluate. I’d love to welcome you to comment. I have an opinion, but I’d rather take a neutral position and provide a platform for debate to advance a science. I’d love to hear both sides.

{ 2 comments… read them below or add one }

Ralph Jans September 30, 2013 at 8:41 am

Just my .02 cents:
1) not enough data for going into the clinic
2) technique not reproducible in top-class research labs such as Weissman’s lab at Stanford. odd.
2) Leukemia article contains language that doesn’t belong into a scientific paper. odd, again.

Reply

Diane Krause October 8, 2013 at 6:38 am

The editorial by Dr. Rataczjak states the primary facts and concerns in his debate. There is no need to attack him for also feeling defensive. You yourself called this a conflict (to call this a war is inflammatory and in accurate).

From a purely scientific point of view, the best way forward is for the groups to interact with respect. Healthy scepicism is a good quality in science. But, disrespect gets you nowhere.

I am one of the scientists who contacted Dr. Rataczjak when members of my lab could not reproduce their data. Now, we sometimes can purify VSELs and sometimes not. So, there is still definitely much to learn about these cells.

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