A Conflicted Sydney Scientist and a New Knee Arthritis Stem Cell Study

Published on Feb 23, 2023

Credit: Shutterstock

I’ve documented what I and others have called “fake” PRP studies. One of the key players involved in one of those studies was David Hunter, a rheumatologist at the University of Sydney. Now David has a new study, one where he’s using stem cells to treat arthritis. Is this another fake study or a real one? Let’s dig in.

Fake PRP Studies

What if you spent many millions of dollars performing a knee arthritis PRP study but never actually treated a single patient with anything approaching the definition of real PRP? Meaning the “PRP” you used was so poorly concentrated that it might as well be whole blood. You might think that if you were a college professor who was heavily involved in designing and supervising such a study, your career is over, right? After all, you wasted big bucks and IMHO embarrassed the university. You would be wrong.

We’ve seen several recent “PRP” studies that did just that. With the minimum definition of Platelet-Rich Plasma (PRP) being at least two times concentrated platelets, they used “PRP,” which didn’t meet that standard. One of those university professors was David Hunter of the University of Sydney. Instead of getting fired, he got this paper testing fake PRP into a prestigious medical journal, which, in turn, missed the salient details (hidden in obscure reference tables) that the study never tested PRP.

How did that happen? In my opinion, it all becomes clear when we look at the university professor who designed, collected data, supervised, and obtained funding for the fake PRP trial. That leads to the Jeopardy-style question, “Who is David Hunter?”

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David Hunter

We would all love to believe that the average university is an institution focused solely on science. However, pharma money has long controlled universities and select professors (7). If you want an example of that “conflict of interest,” let’s explore David Hunter.

David is a professor of rheumatology at the University of Sydney. A COI is a “conflict of Interest” in medicine. The concept is simple. If a physician receives lots of money from outside companies to perform research or for other reasons like being on an advisory board, then practicing physicians should take what he reports or tells us with a significant grain of salt. Medical conferences and medical journals often require these COI listings. However, when I looked up David at the University of Sydney, I saw nothing listed. Hence, I had to look up several papers to determine what he himself had reported elsewhere:

November 2021-“Dr Hunter reported receiving personal fees for scientific advisory board membership from Biobone, Novartis, Tissuegene, Pfizer, and Lilly. No other disclosures were reported.” (1)
-October 2021 (2): “D.J.H. provides consulting advice for Pfizer, Lilly, TLC bio and Merck Serono.”
November 2021 (3): “DJH reports personal fees from Pfizer, Lilly, TLCBio, Novartis, Tissuegene and Biobone outside the submitted work.”
-May 2021 (4): “DJH provides consulting advice on scientific advisory boards for Pfizer, Lilly, TLCBio, Novartis, Tissuegene, Biobone. CL has provided consulting advice for Merck Serono and Galapagos Pharmaceuticals, and receives research funding from numerous pharmaceutical companies (Fidia Farmaceutici, Inter-K Peptide Therapeutics Ltd, Taisho Pharmaceutical Co. Ltd, Concentric Analgesics Inc, Cynata Therapeutics, CEVA Animal Health, Regeneus) through specific services/testing contract research agreements between and managed by The University of Sydney or the NSLHD.”

That’s quite the COI list.

David’s Newest Research (or IMHO COI)

I was intrigued to find a recent radio news story from Australia about knee arthritis and stem cells (5). This featured David Hunter discussing his opinions on physicians using autologous cell therapies to treat knee arthritis. While he was not supportive of using the patient’s stem cells, he discussed conducting a new clinical trial called SCUlpTOR. In that new study, he said he was using stem cells to treat knee arthritis from a company called Cynata. So what’s the deal with that company and technology? In other words, what is David up to?

What is Cynata?

Cynata is a biotechnology company in Australia (6). They state that they have licensed an iPSC technology from the University of Wisconsin. Based on reviewing their website, they take a single blood donation and then cause blood nucleated cells to become induced mesenchymal stem cells that can be scaled from that one donor (8). It’s a nifty idea, other than the fact that there is now a bevy of research about the problems with induced pluripotent stem cells (9,10).

This is how they describe the trial:

“The clinical trial commenced in late 2020 and is entitled Stem Cells as a symptom- and strUcture-modifying Treatment for medial tibiofemoral OsteoaRthritis (SCUlpTOR): a randomised placebo-controlled trial.

The trial is a randomised, double-blind placebo-controlled trial, which will seek to enroll 440 patients with osteoarthritis of the knee. Participants will receive intra-articular injections of Cymerus MSCs or placebo on three occasions over a period of 1 year, and will be followed up for a total of two years from enrolment.”

Are there COIs with Cynata?

When I first read this radio interview transcript, knowing David’s huge number of COIs, I looked up Cynata and tried to determine if he was connected to this company. However, he was not listed on the website as an officer or advisor or listed on a simple Google search as being connected to this company. Nor is there any info that I can find about any COI on the University of Sydney website. However, I realized that this happened the last time as well, meaning that the University of Sydney doesn’t have an easy way to look up the reported COIs of its professors. I even sent an email to the University but never heard back. I then looked at his published papers in medical journals requiring COI statements. An astute reader will have caught that the answer is listed above:

-May 2021 (4): “DJH provides consulting advice on scientific advisory boards for Pfizer, Lilly, TLCBio, Novartis, Tissuegene, Biobone. CL has provided consulting advice for Merck Serono and Galapagos Pharmaceuticals, and receives research funding from numerous pharmaceutical companies (Fidia Farmaceutici, Inter-K Peptide Therapeutics Ltd, Taisho Pharmaceutical Co. Ltd, Concentric Analgesics Inc, Cynata Therapeutics, CEVA Animal Health, Regeneus) through specific services/testing contract research agreements between and managed by The University of Sydney or the NSLHD.”

I also eventually found a statement from the company about Dr. Hunter’s involvement.

Is the University of Sydney a Partner or a Disinterested Third Party Performing the Study?

From Cynata’s website:

“Cynata’s CYP-004 MSC product is the subject of a Phase 3 clinical trial being sponsored by the University of Sydney and funded by an Australian Government National Health and Medical Research Council (NHMRC) competitive Project Grant in addition to in-kind contributions from participating institutions. Cynata will supply Cymerus MSCs for use in the trial and will not be required to contribute any cash to fund the project.”

The University of Sydney, through David Hunter, who is listed as the lead on this study, is a “participating institution.” In addition, note that to the company, this study requires no cash. IMHO, this begs the question of whether the University and Hunter are “partners” in this clinical trial or disinterested third parties.

A Google search revealed that the University of Sydney had previously partnered with Cynata on a heart disease trial using a similar induced stem cell product in 2015 (11). Does the University or anyone at the university own shares in Cynata? I cannot find any regulatory filings to answer these sorts of questions about the company.

Why iPSCs?

Pharma doesn’t like autologous orthobiologic therapies like PRP, BMC, and MFat. Why? They can’t easily be turned into scalable drugs. Even allogenic cells are a problem as they have to be tied to a lot number and specific donors, making things more complex if you’re a big pharmaceutical company. However, a single donor product that can be placed in an unlimited number of vials? That’s got big pharma’s name written all over it.

Summary

This iPSC knee arthritis trial seems to be real and not the same kind of fake PRP study already published by Hunter’s group. What I found creates more questions than answers. For example, is the University a shareholder in Cynata? Is David Hunter a shareholder? Is the university a disinterested third party conducting yet another study, or does it have a financial interest? Why does Cynata state that the university is providing an “in-kind contribution”?

The upshot? Thankfully our favorite Australian conflicted scientist is not performing a fake stem cell study like his infamous PRP study. However, this investigation generated many questions about the relationship between Cynata and the University of Sydney and those running this knee arthritis clinical trial.

_______________________________________________________

After this blog was published, the University of Sydney responded with the email below. Apparently they have no requirements regarding COI disclosures on their university website:

“Dear Dr Centeno,

Thank you for your email.

The University of Sydney does not publicly list the external interests (or any resulting conflicts of interest) of its staff or affiliates. Consistent with the Australian Code for the Responsible Conduct of Research, the University’s External Interests Policy 2010 requires staff members or affiliates whose external interests actually/potentially impact or might be perceived to impact upon the objectivity of any academic presentation or publication in which the staff member or affiliate is involved to ensure that the presentation or publication is accompanied by a public declaration of the relevant interest. It would appear the publications you have listed reflect compliance with this policy requirement.

Please let me know if you have any further questions.

Kind regards,

Matthew

Matthew Wynn (he/him) | Research Integrity Officer
The University of Sydney
Research Integrity, Research Portfolio”

_______________________________________________________

References:

(1) Bennell KL, Paterson KL, Metcalf BR, et al. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA. 2021;326(20):2021–2030. doi:10.1001/jama.2021.19415

(2) Thomas A Perry, Xia Wang, Michael Nevitt, Christina Abdelshaheed, Nigel Arden, David J Hunter, Association between current medication use and progression of radiographic knee osteoarthritis: data from the osteoarthritis initiative, Rheumatology, Volume 60, Issue 10, October 2021, Pages 4624–4632, https://doi.org/10.1093/rheumatology/keab059

(3) Bandak E, Christensen R, Overgaard A, et al. Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trialAnnals of the Rheumatic Diseases Published Online First: 29 November 2021. doi: 10.1136/annrheumdis-2021-221129

(4) Oo WM, Little C, Duong V, Hunter DJ. The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date. Drug Des Devel Ther. 2021;15:2921-2945
https://doi.org/10.2147/DDDT.S295224

(5) ABC Radio Network. What’s the deal with stem cells and knee arthritis? Broadcast Mon 13 Feb 2023 at 12:00am https://www.abc.net.au/radionational/programs/healthreport/whats-the-deal-with-stem-cells-and-knee-arthritis/101965082 Accessed 2/22/23

(6) Cynata Therapeutics. https://www.cynata.com/ Accessed 2/22/23

(7) Harvard University. Edmond $ Lily Safra Center for Ethics. Drug Companies and Medicine: What Money Can Buy. https://ethics.harvard.edu/event/drug-companies-and-medicine-what-money-can-buy Accessed 2/23/23.

(8) Shi Y, Inoue H, Wu JC, Yamanaka S. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov. 2017;16(2):115-130. doi:10.1038/nrd.2016.245

(9) Medvedev SP, Shevchenko AI, Zakian SM. Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine. Acta Naturae. 2010;2(2):18-28.

(10) Young MA, Larson DE, Sun CW, et al. Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell. 2012;10(5):570-582. doi:10.1016/j.stem.2012.03.002

(11) ASX Announcement. Cytnata Therapeutics. Cynata Collaborates with University of Sydney to Evaluate Cymerus™ MSCs for Heart Disease. 30 July 2015. https://files.cynata.com/180/83e12.15.07.30.CynatainHeart.pdf Accessed 2/23/23