A new turn in VSEL controversy

by Alexey Bersenev on July 24, 2013 · 1 comment

in open science, other adult stem cells

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The VSEL cell controversy got much hotter today with a new study by Irv Weissman’s group, published in Stem Cell Reports. The study, basically refutes the claims about pluripotency, hematopoietic potential and even existence of mouse bone marrow VSEL cells. I’ve read it today and it looks very solid to me. Weissman’s paper, with previous 3 studies that we covered before, form a solid opposition to VSEL cell proponents. The discussion is getting hotter and hotter.

Nature posted today a great piece on VSEL controversy and Weissman’s study. I think, Nature demonstrates a good scientific journalism by collecting all voices from both sided of the story. Importantly, it credits all previous three PLoS ONE publications, which built a foundation for scrutiny and criticism of VSEL:

“Weissman’s evidence is a clincher — it is the end of the road for VSELs,” believes Rüdiger Alt, head of research at Vita 34, a private bank for umbilical cord blood in Leipzig, Germany, who last year published the first failure to replicate claims for the cells.

Stem Cell Reports posted rather emotional editorial by Henry Nicholls, where VSEL called an ideology. Nicholls widely cites a prominent stem cell researcher George Daley:

Daley would like to see a rapid resolution to this stalemate. “The folks who are making negative claims should be encouraged to contact the original lab to refine the isolation protocols,” he says. But, he adds, “it should be incumbent upon Ratajczak to share the protocol in a way that’s robust and reproducible. It doesn’t do the field any good if only one lab has the right hocus pocus to make a technique work.”

Even though, VSEL cell were isolated and characterized by few independent labs now, I completely agree with Daley on necessity of reproducibility initiative.

The explanation of VSEL proponents is that “other labs can not catch them during the processing”. As an example, I’d recommend you to read Deepa Bhartiya’s comment. What a tricky protocol! In this sense, Ratajczak’s reply to Nature looks rather weird to me:

Ratajczak thinks that all the published criticisms come down to investigators lacking the technical skill to harvest the correct cells. “Weissman has never visited my lab to witness exactly how we carry out the method,” he says.

Dr. Ratajczak, are you proposing a new standard for reproducibility, where everyone has to come to the original lab to learn? Was it done with iPS or ES cells? As a response to that, Weissman discusses in his paper:

… (2) the experiment as published must be repeatable in many independent laboratories; and (3) the phenomenon described should be so robust that other experimental methods must reveal it.

Yet another respected stem cell scientist – Diane Krause, whose recent paper was cited by Weissman, took Ratajczak’s side:

Diane Krause, who has published evidence that VSELs from mouse bone marrow can differentiate into lung epithelial cells6, agrees. “I can only say that we manage to see these cells,” she says. “One of our postdocs went to the Ratajczak lab and learnt the technique properly.”

I’d say, it would be ok as “scientific exercise”, but it’s not the way to go for translation. High reproducibility and robustness are two essential criteria for translation research into clinic!

Besides some research group, on a side of VSEL proponents those who are about to run clinical trials – Russell Taichman (bone regeneration) and Wojciech Wojakowski (cardiac repair). Apparently, clinicians don’t believe that controversy should be solved before start of clinical trials. What make this story even uglier is a huge cash flow, commercialization and Vatican involvement (Hello NeoStem!) – not good friends of sober scientific debate.

As we can see, the VSEL controversy is reaching a tipping point. A demand for reproducibility initiative and independent validation is very high. There could be a few ways to resolve it – inter-laboratory collaborative effort or expert’s meeting with official statement and consensus. But because of involvement of patents, big money, commercialization, glory/ reputation and church(!), I’d stay pessimistic about clear resolution of VSEL controversy in very near time.

Also read: Are VSELs the Sasquatch of the Stem Cell Field?

{ 1 comment… read it below or add one }

Jozef Dulak July 27, 2013 at 10:18 am

In relation to the request of Dr. Ratajczak that the opponents should come to his lab to learn the proper techniques, I want to inform that we had for two years even better opportunity. Dr. Ewa Zuba-Surma, a co-author of all initial papers on VSELs, and still publishing with Dr. Ratajczak, has been working in our department from May 2009 to June 2011. Hence, we became familiar with the original VSELs methodology and detailed laboratory protocols.

However, I fully support the view that it is crucial that any hypothesis, methodology and results have to be clear and robust enough to be verified in other, independent laboratories. This is mandatory for a scientific finding to be accepted.
Jozef Dulak


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