Smut Clyde would like to talk to you about Very Small Embryonic-Like (VSEL) Stem Cells, which once received the blessing from none other but the Pope himself. Spoiler: these VSEL are made up and do don’t exist. Yet this, like with every religion, is certainly not an impediment to making good money. And this is the bit Smut Clyde would like to focus on.
Before we begin, you must meet a Polish man whose VSEL discovery once impressed the Holy See so much. Mariusz Ratajczak is professor at the University of Louisville, Kentucky, USA. His VSEL papers (almost 30 of them) have been flagged on PubPeer as fraudulent. For example, here is a recycled and a very rude drawing one wouldn’t expect from a good Catholic Ratajczak pretends to be:
In 2011, the Vatican invested one million dollars into Ratajczak’s VSEL business. Two years later, these VSEL stem cells were exposed as a figment of a cheating looney’s inflamed imagination. Yet some believers, or rather greedy sods eager to cash it on fraud, stand by Ratajczak and his VSEL fantasy. In 2020, the University of Louisville educated Elisabeth Bik how to think correctly:
“The University of Louisville found there was no research misconduct. The institution followed its established, thorough, and robust process and made no Findings of research misconduct against Dr. Ratajczak associated with any of the allegations, including all the allegations that continue to persist publicly on the internet. Dr. Ratajczak remains a valued member of the University of Louisville community.”
Ratajczak remains a valued member in his home country Poland as well, he has a professorship and a huge lab at the Medical University of Warsaw, pumped full of money from the Polish state. In 2016, he was awarded the Gold Cross of Merit by then- (and current) president of Poland, Andrzej Duda. The far-right Polish nationalists and dogmatic Catholics love Ratajczak.
Here is an interview with him from a year ago, Google-translated:
“I know people in Poland who, a few years ago, argued that induced cells are the future of medicine and opposed our research. Meanwhile, when it turned out that these cells are dangerous to humans, the sense of this lobbying collapsed. However, if someone wanted to return to it, I appeal to him to simply inject these cells. It happened in medicine that the discoverer applied himself what he discovered, thus proving that his discovery was safe. Unfortunately, this is not the case for iPS cells at the current stage of research. And I am able to inject myself with VSEL cells at any time.“
The interview was made on the occasion of the 5th Baltic Stem Cell Meeting in Warsaw in October 2022, it opened with plenary lectures by Ratajczak’s VSEL collaborator from Louisville Donald Miller and someone from Bulgaria named Igor Resnick, then Ratajczak talking about VSEL, followed by one VSEL session, then another one. Also in non-VSEL sessions, VSEL were discussed as cure for lung injury, COVID-19 and testicular deficiency. One invited speaker was a French collaborator of Ratajczak’s, David Smadja, and he spoke not only of “VSEL: past, present and future“, but also of “Trust, Fake news and Covid-19: how public communication have build a new area“. Another speaker was Prof. Janina Ratajczak from University of Louisville (guess who she’s married to), who spoke of VSEL mystery populations in the bone marrow.
The conference ended with a VSEL workshop at the Laboratory of Regenerative Medicine at the Medical University of Warsaw. That lab is run by Ratajczak and his former postdoc turned VSEL acolyte Magdalena Kucia, who spoke at the conference of “Stem cells and Covid-19“, as well as of her patented “effective method of ex vivo propagation of VSELs cells in in vitro cultures and their differentiation into progeny cells of various tissues.” I trust she and Smadja can cure COVID-19 with VSEL. What we sure know: they all feel very safe, secure and supported by their employers. Look at this recent paper:
Alison Domingues , Elisa Rossi , Kamila Bujko , Grégoire Detriche , Ulysse Richez , Adeline Blandinieres , Magdalena Kucia , Janina Ratajczak , David M. Smadja , Mariusz Z. Ratajczak Human CD34 very small embryonic-like stem cells can give rise to endothelial colony-forming cells with a multistep differentiation strategy using UM171 and nicotinamide acid Leukemia (2022) doi: 10.1038/s41375-022-01517-0
Kucia holds many VSEL patents with Ratajczak, some of them quite amusingly list his Louisville colleague Roberto Bolli as co-inventor. Bolli is infamous as Piero Anversa‘s partner-in fraud, peddling non-existent heart stem cells until the hammer came down in 2018, so you see why Bolli was attracted to Ratajczak’s VSEL cult. Unsurprisingly, also Kucia, just like Ratajczak’s wife, has a professorship at University of Louisville.
The whole VSEL farce seems to be the Polish version of Laurentiu Popescu‘s Romanian telocytes. Those are also tiny, invisible, and non-existent pluripotent stem cells.
In Memoriam: Professor Laurentiu “Telocyte” Popescu (1944-2015)
“The idea to call the newly discovered cells telocytes came to me during a break at the Vienna State Opera” – Don Lorenzo aka Preda
Yet another invited speaker at the Baltic Stem Cell Meeting 2022 was a certain Prof. Deepa Bhartiya, and it she and her business partners, the Indian family named Tripathi, who Smut Clyde wants to tell you about. In fact, Ashish Tripathi was also there in Warsaw, photos show him in audience, and chatting with Smadja.
Stop trying to make VSEL happen! (Pixie Dust and Pathological Science)
By Smut Clyde
Dr Paul Knoepfler over at The Niche is not well-pleased with VSELs or “Very Small Embryonic-Like stem-cells”. He has been non-well-pleased for a while.
Writing at Science Integrity Digest, Dr Elisabeth Bik focused on image duplications and overlaps in VSEL-related papers. The executive summary for now is that no Museum of Pathological Science would be complete without an exhibit on VSELs, alongside telocytes (and N-Rays, Cold Fusion and the Canals of Mars).
Some explanation of VSELs is probably in order. But that would be too easy. Instead, I want to introduce you to Ashish Tripathi, merchant banker turned Stem Cell scientist. This allows me to repurpose two old Twiddle threads, and our host’s previous VSEL coverage in Friday Shorts.
Tripathi was co-author of two recent papers promoting a protein OCTA-4A as a blood-borne biomarker of VSEL activity. I’m not sure whether it is produced by the VSELs themselves or by the cells around them. Either way, it is an infallible indicator of cancers (which invariably originate as rogue VSELs). He goes further, promising not only that his blood-test for OCTA-4A can detect covert cancer years before it shows its presence, but can even indicate what kind of cancer. David Sinclair takes this flim-flam seriously so I’m convinced.
Tripathi’s claim also prompted uncurbed, uncritical enthusiasm from our other old friend, full-spectrum fraudster Deepak Chopra.
Guilty pleasures of meditating with Deepak Chopra
Smut Clyde will take you on a meditative Ayurvedic trip where the most respectable of research institutions and their world-renowned academics were caught dancing with the Guru Deepak Chopra himself. Famous cardiologist and medical writer Eric Topol and the Nobel Prize winner Elizabeth Blackburn were just two most prominent US academics listed on Chopra’s Panchakarma…
Chopra’s usual disdain for reductive, mechanistic, non-integrated medicine goes out the window when someone from India is doing the reducing and mechanising. Hence this Youtubular mutual-admiration society:
Tripathi’s churnalistic tabloid offensive began with stenographic ballyhoo in the New York Post on one side of the Atlantic and the Express on the other. “Being applied in hospitals across the United Kingdom” is a term of art best translated as “A UK gastroenterology oncologist, Sherif Raouf, is keen to begin a clinical trial”. I looked up “Ballyhoo”, and evidently it is not just a village in Ireland!
It turns out, though, that Tripathi is heavily invested in promoting VSEL / OCTA-4A tests, with companies Tzar Labs and Epigeneres Biotech founded to fill that gap in the market. How well the tests work is irrelevant from the perspective of sales and share prices. Also he has prior form for retractions and making stuff up. I copied the UK oncologist into a tweet to urge some caution but never heard back… alas, Tsar Labs had already recruited Dr Raouf to their Medical Advisory Board.
This carcinogenic villainy from VSELs is something of a heel-turn, as they say in Kayfabe. They were previously famous as the agents of regeneration, ready to rebuild and revitalise organs, needing only to be activated… much like every other monetarised kind of stem-cell. They are not my first choice of therapeutic injection if they also cause all cancers.
None the less, here’s Deepa Bhartiya, explaining to Dr Bik that the best evidence for the existence of VSELs is the dismal failure of all the other much-vaunted stem-cell therapies to deliver on their promises.* Since it is axiomatic that some stem-cell therapy must work, the successful cell-types must be the ones that haven’t been tried yet, which leaves VSELs. I hear her comment in the voice of Bullwinkle assuring Rocky that this time the trick will work for sure.
Deepa Bhartiya’s interest in the topic comes from her specialty in reproductive biology, and more specifically in restoring fertility (e.g. in ovaries damaged by chemotherapy).¹ She seems to have left academia now to become Research Director at Epigeneres Biotech and at Tzar Labs.
Then PubPeer nuisance and occasional For Better Science contributor ‘Cheshire’ turned his easily-distracted attention to Bhartiya’s oeuvre.
One paper has been retracted, after its illustrations turned out to have been pillaged from elsewhere OOPS SORRY “The authors have been unable to locate the original images“. That was a collaboration with Tripathi that was essentially an advertisement for a fertility-restoring nano-formulation of resveratrol. Manufactured by Epigeneres Biotech Pvt. Ltd. (Director: Ashish Tripathi; CEO: his brother Anish; CSO: their father V. K. Tripathi)**.
A second retraction. In PubPeer comments, Dr Bhartiya regretted that software assistance such as ImageTwin had not been available in 2011 to alert the authors to the fact that they had manipulated and duplicated images.
For a third paper, the authors have asked the journal to correct the Supplementary Figures.
Another request for a Correction! PRO-TIP: Even if you feel that it’s legitimate to sew a lot of image fragments into a single composite (to make up for the scarcity and invisibility of the microscopy artifact cell type that you’re studying), duplicating those details does not improve the overall effect.
Some might wonder why the journal editors would settle for a correction rather than retracting the paper after discovering such epic image manipulation / creation. Wonder no more – for as with Stem Cell Reviews & Reports, the editors of Journal of Ovarian Research include one Deepa Bhartiya, who edits / contributes to a number of journals in this cross-over intersection between stem-cell biology and human fertility.
In the case of two other papers, some patient persuasion was required before Dr Bhartiya accepted that they used the same image (modulo a 180° flip). Ultimately she conceded Actinopolyspora biskrensis‘s point and replaced one of the copies in a Correction. However, Condylocarpon amazonicum (another regular PubPeer contributor) still has unresolved issues about Fig 3 from the same paper.
I will spare you the details of the Correction for Figs 3 and 7 from “Further characterization of adult sheep ovarian stem cells and their involvement in neo-oogenesis and follicle assembly” (Patel et al 2018).
For a survey and summary, readers may benefit from “Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead” (Bhartiya et al 2016). Here “critical review” is used with the special meaning of “critical of VSEL skeptics”. Dr Bhartiya begins with the observation that VSELs and iPS cells were both reported in 2006, but only the latter discovery resulted in a Nobel Prize chiz chiz.
That unsung un-Laureated discoverer of VSELs was Mariusz Ratajczak – a giant in the field, judging from the number of honours and editorial roles heaped upon him. His research output was the focus of that 2020 Science Integrity Digest post, which is another honour, of a kind. Not to forget the honour of regular attention from Friday Shorts. A retraction ensued, and a correction and Editorial Expression of Concern, but in general the PubPeer critiques were ignored.
Those critiques came as a surprise to the Corresponding Author of “Characterization of Human CD8(+)TCR(-) Facilitating Cells In Vitro and In Vivo in a NOD/SCID/IL2rγ(null) Mouse Model” (Huang et al 2016), who lamented that if only the emailed notifications had reached them at the time, they might still have had high-resolution originals of the problematic panels. Dr Ildstat stood by the unaltered authenticity of Figure 1C (“The photographs were taken directly from the microscope and have not been modified“) while reminding readers that they were the responsibility of the first author.
That is where we started, and it is time at last to explain the topic of this post. The theory goes that VSELs retain their embryonic state of pluripotency – Protean and undifferentiated, capable of specialising in any area of cellular expertise – much like me opinionating in PubPeer. We know that because they lack the distinguishing protein markers of differentiated tissues.
They are also biologically quiescent until needed; very rare; and very small. The usual laboratory exercises of concentrating and isolating them don’t work… Ratajczak’s special sauce and deft hand are required. And when other researchers fail to find them, or conclude that they’re microscopy artefacts, that simply provides more evidence that VSELs are real because they display those attributes of rarity, molecular anonymity, smallness and quiescence. Perhaps a better acronym would be “PD”, Pixie Dust.
Theologians had been bedazzled by the prospect of embryo-free stem-cell research and in 2011 the Vatican invested $$$ in a company “NeoStem Inc“, set up to commercialise VSELs, with Ratajczak as its board member. But the clerical endorsement was outweighed in the court of scientific opinion by Irving Weissman‘s 2013 failure to replicate Ratajczak’s claims… hence the lack of Nobel Prizes and indeed of canonisations.
Nature wrote in 2013:
“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.”
One of NeoStem’s consultants, back in those heady days, had been Chris Centeno, a leading stem-cell practitioner quack. An erstwhile pain-medicine specialist who founded the Regenexx chain of stem-cell clinics (including branches in the Cayman Islands for procedures that aren’t legal in the US). In his blog, Dr Centeno reckoned that Weissman’s negative findings were driven by Conflicts of Interest, though he didn’t bother spelling out what those were:
“If Dr. Ratajczak at the University of Louisville was the rebel alliance, then Irv Weissman at Stanford would be the Empire […] Irv is very much the stem cell establishment and Ratajczak is very much the upstart wanting to reorganize the way the establishment sees how stem cells work.”
This left Centeno free to ignore the evidence and opine that VSELs probably exist, though he questioned the practicality of any therapeutic applications. Which is to say, he wants to discourage VSEL competition without dismissing the concept entirely in case he wants to add it to his repertoire at some future date. See, I bring you both sides of the debate!
C. amazonicum argued in a PubPeer comment that a human spermatozoon is essentially a collapsed haploid nucleus with an outboard motor. The cargo of haploid chromatin is packed up tightly and marked “Not Wanted on Voyage”, unavailable for transcription into mRNA. While VSELs are even smaller – leaving little room for the rest of the machinery of cellular metabolism. So how do they function? They are comparable in volume to red blood corpuscles, which downsized by jettisoning their nuclei and becoming cell-shaped zombies. Thus (Condy concluded) VSELs are not plausible as actual viable cells, however quiescent. Ultracentrifuge detritus? Probably we’ll never know.
* Is it possible to vaunt too much? We really need Official Health Guidelines about the recommended amount of vaunting per day.
** A third brother, Amish Tripathi, is a celebrated writer. His role in Tzar Labs is as Director / Advisor. I hasten to add that the company is not just authors and merchant bankers and Masters-of-Business-Studies; they have scientific and medical expertise on board too. As well as Dr Bhartiya, we find Dr Amit Dilip Bhatt, Director and Senior Medical Oncologist from the Avinash Cancer Clinic. Dr Bhatt is a a true believer, credited with contributing design advice and patients to Tripathi’s 2021 “Quest for Pan-Cancer Diagnosis/Prognosis” paper.
“This is an example of Indian scientists and an Indian startup creating a novel breakthrough which will have a lasting impact on cancer treatment,” say Dr A D Bhatt and Dr Anantbhushan Ranade, respected oncologists and directors of Avinash Cancer Clinic.
Swarajya magazine (2021)
While Deepa Joshi – once Head of Clinical Research at the Avinash Clinic – now fills the same role at Epigeneres.
Has anyone informed the UK NHS that they’re in a Key Partnership with Tzar Labs?
Note by LS:
Neither Smut Clyde nor myself found any financial connection between Ratajczak’s gang and the Tripathi VSEL businesses. Yet it is utterly unlikely the Tripathi family would cheat the patent-holding for Epigeneres / Tzar Labs scams with VSEL. Otherwise there would be lawsuits and Ratajczak certainly wouldn’t be hosting Bhartiya and Tripathi at his Warsaw conference last year. Maybe they brought Ratajczak his cash in a suitcase, for tax reasons?
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