July 13, 2020

The Niche

Knoepfler lab stem cell blog

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

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?

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