VSEL controversy: Dulak’s group response to Ratajczak

by Alexey Bersenev on March 11, 2014 · 1 comment

in other adult stem cells

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We’re continue to follow ongoing controversy, related to so-called Very Small Embryonic-Like Stem Cells (VSEL). In the last update, Mariusz Ratajczak’s group, which discovered VSEL cells, addressed some controversial issues and responded to criticism. Last week, Jozef Dulak’s group responded to Ratajczak in commentary, published online in Stem Cells and Development journal.

Dulak argues that simulation of their sorting strategy by Ratajczak is incorrect and “misleading”.

First, we have never performed gating in the way named by that Suszynska et al. refer to as “simulation of Szade et al. sorting strategy”. One can easily see that dot-plots presented in the “simulation” do not correspond to the dot-plots in our article [3].

In fact, Ratajczak “simulation” looks different from original Szade’s data. Next, they argue that VSEL were not missed in applied gating strategy and “classical” VSEL markers were used for sorting and analysis:

It must be emphasized that we sorted only the cells which fulfilled the criteria described for VSELs (phenotype: Lin-Sca-1+CD45-FSClow, with HSC/VSEL size ratio of 1.7 versus 1.8 described earlier). It is worth mentioning that the Weissman group obtained the same results as ours [5], strictly following the gating strategy described in earlier papers, recommended by Suszynska et al. [7].

and

iii) “employing some selection markers that are unproven as VSEL markers (e.g., c-kit)” [7].
We showed that c-kit and KDR expression defined three distinct subpopulations among Lin-Sca-1+CD45- phenotype that were proposed to identify VSELs [3]. However, we did not use c-kit and KDR to select VSELs in functional evaluations: Oct-4A expression and hematopoietic differentiation on OP9 cells [3]. For these assays we sorted events with general Lin-Sca-1+CD45-FSClow phenotype [3] as proposed by the group that initially claimed to isolate VSELs [1]. Therefore, this argument cannot be used to explain the negative results obtained in the functional tests.

Dulak addresses all Ratajczak comments point-by-point and, at the end, responds to “contacting lab-originator” issue:

vi) “most of these difficulties could have been eliminated or greatly minimized if these groups
had first contacted us” [7].

… most of the authors of the Szade et al. paper had the opportunity to work on the isolation of VSELs with the member of the team that initially had characterized this population, within one project that was carried out
in the same department. Nevertheless, the data were not reproducible.

As a representative of “VSEL deniers” (term, coined by Ratajczak) side of debate, Dulak’s concluded:

… we do not agree with objections raised by Suszynska et al. [7], and we maintain the conclusion that the hypothesis implying pluripotent features of VSELs in adult bone marrow has not been independently confirmed.

The bottom line:
The controversy still here! Seem like nothing has changed since Weissman’s grop “dropped anti-VSEL bomb” – a camp of VSEL proponents against of camp “VSEL deniers”. I’d like to post a few questions for discussion:

  • Did detailed VSEL protocols have any impact of the other camp?
  • How to tackle reproducibility issue, if at least 3 independent groups still can’t make it?
  • What is the best way to solve VSEL controversy?

I wonder if Alt’s and Weissman’s group will continue discussion? My dream is to see this discussion happening rapidly and efficiently online (blogs/ PubMed Commons/ PubPeer). But as of now, we have to wait months (!) to see every new comment in printed journals.

{ 1 comment… read it below or add one }

jose fontanals October 22, 2015 at 12:18 am

were are usig vsels to treat ilnes

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