A close look at new stem cells for COVID trial pub

I’ve been following the stem cells for COVID arena for more than two years. During this time researchers have launched scores of trials. A few have been published including a new one.

It’s been a wild ride that at times has included politics and an odd cast of characters. There was Rick Perry and also Rudy Guiliani getting in on it.

stem cells for covid, kim knoepfler 2021
Map of geographic distribution of COVID-19 cell therapy trials. The top number is the total number of
trials in each country and the number underneath reflects the anticipated most impactful trials in that country.  Kim and Knoepfler, 2021, Regenerative Medicine.

Clinical trials of stem cells for COVID-19

On the science side, so far nothing clinical trial-wise ever seems to get clarity. However, at the same time many small, uncontrolled studies are touted as encouraging in publications. My former student Mina Kim and I found that most cell therapy trials for COVID-19 at that time earlier in the pandemic were too small and not properly controlled and designed to yield conclusive results.

It’s tempting to get caught up in the over-exuberance. I’ve even thought a few of the better-designed or relatively not-so-small studies were encouraging at first, but as you dig into them there are always limitations and potential other issues.

What we need are large, controlled, blinded clinical trial data. That’s not what we’ve gotten so far though.

Stem cells for COVID
Trial testing stem cells for COVID. Fig. 2. Gregoire, et al. Frontiers Immunology. Two notable limitations to this study are the controls were unmatched ones selected later and the MSC group is only N=8.  In addition to not being controlled, the study was not blinded. The controls select later were older than the MSC group as well.

New study highlights challenges

The new small trial published in Frontiers in Immunology is another example of a study that is very limited. The paper, entitled Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial, seems encouraging on the surface.

Somehow, 100% of the MSC infusion group survived, which seems almost too good to be right.

There were no matched controls in the study from the beginning. So how do we know what meaning to give the results? The team selected unrelated controls retrospectively from other data, which is not a strong approach.

The MSC recipients also received standard COVID care including steroids. These drugs are thought to work by a similar mechanism to help COVID as the one proposed for MSCs. For that reason, it would be notable if MSCs gave a benefit above and beyond steroids.

Another limitation to the study is that the retrospective control groups were older (control matched) and much older (whole cohort) than the MSC group.

Overall, the design, small size, and other issues make making conclusions very difficult despite the seemingly encouraging results.

I’m hoping we’ll see some large, well-controlled, blinded studies soon to clarify whether MSCs have much promise here. I’m still skeptical. Also see this STAT News piece: For now, stem cells for Covid-19 are still mostly a shot in the dark.

6 thoughts on “A close look at new stem cells for COVID trial pub”

  1. Dr. Knoepfler you wrote about this one remember, a placebo controlled phase 2 trial for covid-19 using umbilical cord mesenchymal stem cells (MSCs)

    Therapeutic Solutions International is the company that bought the rights to the umbilical cord MSCs that were used during this phase 2 trial, and they’ve already started the phase 3 trial. Well I’m assuming you’ve never heard about Therapeutic Solutions International, stock symbol TSOI. This is a small biotech company being run by Tim Dixon and Dr. Thomas Ichim. Are you familiar with Thomas Ichim?

    I own stock in TSOI, I think the phase 3 trial will turn out to be very successful. If the phase 3 trial turns out to be a smashing success, then the FDA will most likely give them approval, which would make them the first company to ever gain approval from the FDA for umbilical cord MSCs. Do you hear what I’m saying? I think TSOI might just be the first company to ever gain approval from the FDA for the use of umbilcal cord MSCs.

    Here’s the link to the phase 3 trial https://therapeuticsolutionsint.com/therapeutic-solutions-international-announces-launching-of-phase-iii-clinical-trial-for-treating-covid-19-lung-damage-using-its-jadicell-universal-donor-stem-cell-drug/

    I first learned about mesenchymal stem cells thanks to Joe Rogan. And I’ve been researching the stuff for years now. I am convinced that umbilical cord MSCs are NOT snake oil, I think umbilical cord MSCs will revolutionize modern medicine as we know it!!!! I mean I saw how excited you were about the recent trial at UC Davis where they gave placenta derived MSCs to babies, and it appears to have cured their spina bifida. I’m telling you placenta/umbilical cord MSCs are revolutionary!!!! I want to mention exosomes as well, it appears MSC derived exosomes are revolutionary as well.

    So what say you Paul?

    1. @Scott,
      The bottom line is if you have an idea that MSCs can help a specific condition, you’ve got to prove it with really good data.

      Too often those promoting MSCs have little-to-no good data but they nonetheless hype the cells. Hundreds of people are already selling supposed MSC therapies to make profits.

      If Therapeutic Solutions International’s Phase III is successful then I’ll be very happy. Same goes for any other effort involving MSCs. But you need top-notch data.

      I really don’t care which types of cells help people as long as it’s proven actually safe and effective.

      We have to hold other possible therapies using different stem cell types to rigorous standards too including iPS cell-related clinical work. For example, I’ve posted before about iPS cell experimental efforts that had issues like mutations or a tumor in one case. Fortunately, those have been very rare.

      It’s exciting to see the work here on spina bifida move forward and seem encouraging so far. There’s still a lot more the team needs to do.

  2. @LLBaker Placebo controlled double-blinded studies are essential for stem cell treatments but not so much for COVID “vaccines” (they’re not) or other pretty-much-untested drugs liks Remdesivir or Paxlovid.

  3. I’m sure you have seen this, but an important update in this space for MSCs for COVID:
    Kirkham AM, Bailey AJM, Monaghan M, Shorr R, Lalu MM, Fergusson DA, Allan DS. Updated Living Systematic Review and Meta-analysis of Controlled Trials of Mesenchymal Stromal Cells to Treat COVID-19: A Framework for Accelerated Synthesis of Trial Evidence for Rapid Approval-FASTER Approval. Stem Cells Transl Med. 2022 Jun 27:szac038. doi: 10.1093/stcltm/szac038. Epub ahead of print. PMID: 35758400.
    Will be keeping an eye on this as more data is added

  4. It would be nice if you would focus on the successes rather than making yourself a self appointed master of double blind studies….pure bs

  5. Dear Admin:

    If Niche readers want to learn about a recent meta-analyses of the results of a large number of clinical trials with variably sourced MSCs for treatment of COVID-19-associated Acute Respiratory Distress Syndrome (ARDS), they should check out Asymmetrex’s “A Stem Cell Count Would Have Made It Better” forum #19, posted on July 6, 2022:

    James @ Asymmetrex®

Leave a Reply