COVID-19 stem cell trials pile up during novel coronavirus outbreak

2019-nCoV-CDC-23313 COVID 19
Diagram of 2019-nCoV virus that causes COVID 19. Image source US CDC.

Could stem cells help patients with the novel coronavirus disease COVID-19?

It’s hard to say at this point. Is it worth doing trials during the outbreak to find out?

Three new clinical studies have popped up on Clinicaltrials.gov investigating the potential of stem cells to help patients infected with the new coronavirus 2019-nCoV. Update, the number of trials on Clinicaltrials.gov is now five as of March 1, 2020.

These stem cell COVID-19 studies are part of a tally of 80 or more new clinical trials to tackle the new viral illness. That number is likely to go over 100 soon.

2019-nCoV-CDC-23313 COVID 19
Diagram of 2019-nCoV virus that causes COVID 19. Image source US CDC.

Here are the current three Clinicaltrials.gov stem cell coronavirus studies:

Updated: note that the WHO’s trial database finds 15 total studies as of March 1 from a search for stem cells for COVID-19 and these, which partially overlap with the Clinicaltrials.gov results. There were only 10 trials as of February 19.

These studies overall are mostly focused on IV infusions of mesenchymal stromal/stem cells  or MSCs.

It was not immediately clear to me after I did these searches as to why IV administration of MSCs would have potential benefit to patients fighting the novel coronavirus, but I guessed part of the proposed idea was focused on modulation of immune system function and that was indeed a major emphasis. The second trial from Clinicaltrials.gov listed above has the most thorough background and purported rationale for use of MSCs:

“Mesenchymal stem cells (MSCs) are one of the most studied and important adult stem cells. A large amount of evidence shows that MSCs can migrate to and return to damaged tissues, exert strong anti-inflammatory and immune regulatory functions, promote the regeneration and repair of damaged tissues, resist apoptosis and inhibit tissue fibrosis, and reduce tissue damage. Many studies have shown that the anti-inflammatory effects of MSCs can significantly reduce virus-induced lung injury and mortality in mice. Studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses by reducing the levels of proinflammatory cytokines and chemokines and reducing the recruitment of inflammatory cells into the lungs. Compared with MSCs from other sources, human umbilical cord-derived MSCs (umbilical cord MSCs, UC-MSCs) have been widely used because of their convenient collection, no ethical controversy, low immunogenicity, fast self-renewal and strong proliferation ability Research on the treatment of various diseases. Early research in this laboratory used UC-MSCs to intervene in endotoxin (LPS) -induced acute lung injury in mice, and confirmed that UC-MSCs can significantly reduce inflammatory cell infiltration in lung tissue, reduce inflammation in lung tissue, and significantly improve lung The structure and function of tissues protect mouse lung tissue from endotoxin-induced damage.”

This seems like a long shot to me in terms of achieving significant efficacy in human patients, meaning significantly reducing the severity of COVID-19.

Although some IV MSCs can end up in the lungs of human patients, it’s not very clear what they do there as well as how many are alive and for how long.  In the context of severe lung disease, I’d predict that most MSCs that make it to the lungs will not survive long enough to be helpful.

At least one simple PubMed search found just 11 mostly mouse studies that don’t together make for a very rock solid foundation. I’m sure there are more studies that could be found with other searches though.

Also, if the infused MSCs have a broader immunosuppressive function, they could actually make the COVID-19 worse in some patients as well so there are real potential risks here.

On the other hand, given the severity of the outbreak and pandemic potential, trying some different ideas including things that may be long shots is probably worth it in my view if the studies are well-designed.

Note that there are important ethical considerations to starting trials during outbreaks. Not all proposed outbreak treatment studies are likely to be worth doing. It’s hard to gauge the potential risk-benefit ratio for each trial as dozens of new studies pile up.

What do you think of the idea of testing IV MSCs for COVID-19?

13 Comments

  1. Hi Paul,
    Thanks for the update – and I agree with your views .
    Also may I add my own concern which is the logistics.
    How many cells are required to treat how many patients ? The logistics don’t work.
    Su
    LIFNanoRx
    Cambridge UK

  2. What pluripotent stem cells have to do with viral immunity?
    That the US authorities allowed those clinical trials to take place just amazes me in their sheer lack of scientific foundation.
    So, what would the stem cells are supposed to differentiate into to contribute to a viral clearance process? How would they turn into a host mechanism to fight specifically against Covid-19?
    Last and not the least, how long the whole process takes to reach an efficient cellular mechanism to eliminate the virus in a way or another?
    Not to speak about whether the trials would actually go beyond Phase I, notwithstanding Phase II.

  3. Hallo Paul,
    I remember we discussed the PRP-therapy several times here. Each time we had really interesting discussion. Now Regenexx has published an article concerning your blog.

    “Now let’s compare that evidence against what Paul has called “unproven” on his blog, PRP used to treat knee arthritis. In fact, we can even compare PRP to these two traditional, but “unproven” therapies above. There are two randomized controlled trials in patients with knee arthritis where PRP was compared to a cortisone injection and the PRP was found to be more effective (5,6). There are also 15 randomized controlled trials where PRP was compared head to head to hyaluronic acid injection. In 13 of those high-level studies, PRP was found to be superior to HA (7. 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 20, 21). Two of those RCTs demonstrated that PRP worked about the same as a hyaluronic acid injection (15, 19).
    So Paul clearly has his facts backward. PRP is more “proven” than what’s commonly used for injections to treat knee arthritis. How’s that for a false dichotomy? Has this come out in a single news piece that Knoepfler has participated in? Not that I can find.”

    I already have experience with PRP therapy and I am still very interested, if the effectiveness of PRP is proven or not. In my opinion the cited studies are very interesting and I would be grateful if you would take up the subject again to discuss the efficacy of the PRP therapy in another post.

    Thanks,

    Richard

  4. Clinical trials for Cornoavirus Covid-19 seem premature. The rationale for using stem cells for viral infections is the growing evidence that stem cells and the molecules that they release are directly part of the innate and adaptive immune systems and have been found to fight viral infections and resolve the inflammatory response.

  5. Whether it’s the use of MSCs for viral pulmonary infections or PRP for orthopedic conditions, which should come first, opinions or evidence? And when we do have clinical evidence, do the opinions really matter?

  6. Paul,
    People are dying and you want to do well designed studies? Theoretically, injecting stem cells IV makes sense as most of them get trapped in the lung. Through local paracrine effect, they can help with lung injury and through exosome production they can possibly fight the virus. There are numerous clinical studies showing that IV stem cell infusion if properly performed is safe. When there are no effective anti-virals, what do these critically ill and dying patients have to lose?

  7. I agree with Dr. Atluri. There are case reports out of China treated severely ill and likely to die patients with severe ARDS. History has shown us that often the most important medical discoveries are developed during times of war, and although COVID-19 is not the same as mortars, artillery shells, etc, it is indeed causing war like conditions. So, in my opinion, it is entirely reasonable to try this on a carefully selected basis when patients seem to be dying.

  8. I agree with both David and and Dr Atluri.
    Also – we need to move asap – and reach scale up asap.

    LIF is a growth factor able to replace stem cells – and rhLIF has already been through phase II clinical trials showing safety.
    LIF is essential to control the cytokine storm in pneumonia. As we age, levels of LIF decrease whilst levels of inflammatory IL-6 increase.

    IL-6: The Wuhan Study: Zhou et al Lancet March 2020 has shown IL-6 is a predictive risk factor for hospital death from COVID-19 pneumonia.

    LIF directly opposes IL-6 : this is the mechanism of LIF’s control to prevent overwhelming cytokine storm.

    I need help …please….everything is in place to produce cGMP LIF at scale with regulatory approval, but the funders preferred to fund vaccines (treating the Virus) rather than LIF (treating the patient). With $3M we can reach patients with a pure safe therapeutic to protect the lungs. asap

    [email protected]

    • Interesting idea and this brings us back to a classical drug therapy. Can you share any data that demonstrates efficacy of LIF in animals models of coronavirus infection – or any viral infection? If the data is good enough you might get a fast track from the FDA.

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