Home Cellular health For now, stem cells for Covid-19 are mostly a hit in the dark

For now, stem cells for Covid-19 are mostly a hit in the dark


TThe uncertainty of how to effectively treat Covid-19 is proving to be an opportunity for those interested in stem cells.

It’s such a hot area that there are dozens of ongoing clinical trials testing different types of stem cells and other cells against Covid-19. And many stem cell clinics have started offering cell therapies for Covid-19 over the past year.

As a stem cell researcher, I don’t think this approach will be a transformative way to treat Covid-19, but I fear the buzz around it could hurt.


How did we get into this situation?

In the human body, a skin cell is a skin cell, and when it grows and divides, becomes another skin cell. The same is true for other types of cells, except stem cells. One of the amazing things about them is that they can transform into other specialized cells, some of which have the potential to treat specific diseases. The most powerful stem cells, called pluripotent stem cells, can turn into any type of cell.


Adult stem cells, which also hold great promise but are not as flexible, are also often mistakenly thrown under the same large, powerful umbrella of ‘stem cells’.

As a result, many people believe that stem cells in general can turn into any type of useful cell. So it is perhaps not all that surprising that the public – and even some scientists – make the mistake of thinking that stem cells can also be used to treat any type of health problem, as if it were of a kind of universal healing ointment.

Not so. The sad fact is that the FDA has approved relatively few cell and gene therapies, and only a tiny subset of them use genuine stem cells.

Yet the more harmful or fatal the disease, the more likely it is that “stem cells” will be launched to fix it. It’s an equation for false hope and other issues like wasted research dollars. The use of stem cells to treat diseases also poses health risks that must be carefully evaluated.

This overexuberance and even this hype has now been going on for over a decade.

Enter Covid-19, which has been like a wishful thinking magnet on stem cells and cellular medicine.

IIn just about all Covid-19 stem cell-related clinical trials conducted, specific experimental cell therapy launched against the disease had never been seriously considered before for viral, or even respiratory, disease. Before the emergence of the pandemic, these experimental cell injections were primarily studied for diseases such as cancer, heart disease, spinal cord injury, Parkinson’s disease, and many more. The sponsors of many of these clinical trials have made a sharp turn towards Covid-19.

In the United States, the Food and Drug Administration not only made this change possible, but actively facilitated it by authorizing a wide range of trials. Remarkably, the FDA did this even though many trial sponsors did not have relevant preclinical data. Rather, most of the sponsors and the FDA appear to rely on limited preclinical and clinical data from a few other sponsors. This is a very unusual situation.

Based on recently published research that my student, Mina Kim, and I performed on trials registered on ClinicalTrials.gov and its counterpart, the Chinese Clinical Trials Registry, there appears to be a similar turn of events with regulators in China.

The FDA has even gone so far as to give the green light to cell medicine trials for Covid-19 from certain sponsors that are unproven stem cell clinics or have some sort of connection to them, at least one or more of which the agency has previously warned against the use of unapproved therapies.

At the heart of this matter is the question of the raison d’être. A single common rationale – but in my opinion, fragile – is given for most of the cell therapies tested for Covid-19 around the world. It is this: In some contexts, cells known as mesenchymal or stromal cells (usually by the acronym MSCs) have anti-inflammatory and immunosuppressive functions. So that they strength attenuate overactive immune responses to Covid-19, such as cytokine storms that can cause severe damage to the lungs and other tissues.

To my knowledge, only one stem cell company had directly relevant data from before the pandemic. Athersys had tested its MultiStem product against acute respiratory distress syndrome, which is a component of severe Covid-19. While the results were mixed, I would say Athersys was warranted to conduct a Covid-19 trial with MultiStem, even if it was a bit long. But dozens of other trials then relied on data from Athersys and the general idea that stem cells could reduce inflammation.

Additionally, the proposed mechanism by which stem cells quench inflammation greatly overlaps with the proven beneficial mode of action of affordable and generally safe steroids, which are now widely used to treat Covid-19. With steroids as the accepted standard of care here, how can stem cells do better?

They probably can’t.

And to complicate matters, it will be extremely difficult for stem cell clinical trials to distinguish stem cell-specific signals in individual patients from steroid-related benefits.

All of this raises questions for me: Why have dozens of sponsors followed the path of clinical trials to treat Covid-19 using mesenchymal stem cells or similar cells? The excess of exuberance to help stem the pandemic? Will it be good for the result? Why has the FDA given the green light to trials so often? Politics? Pandemic exceptionalism?

Whatever their reasons, Mina and I found over 79 cell medicine trials for Covid-19 listed in trial databases. It seems excessive.

We have also found that most Covid-19 cell medicine trials use MSCs or similar cells, but these are not equivalent to each other or to Athersys’ MultiStem product. Athersys even wanted to say that MultiStem cells are do not MSC. To further complicate matters, our data shows that sponsors use MSCs taken from a mishmash of sources: umbilical cord blood, the wall of the umbilical cord itself, bone marrow, adipose tissue (fat). and dental pulp. These cells are not interchangeable. They probably each have different potential for effectiveness and present different risks. For example, MSC preparations from different tissues made in different laboratories likely contain very different numbers of actual stem cells.

More worryingly, our analysis found that the vast majority of cell therapy trials for Covid-19 lack rigorous design features on which to draw solid conclusions. In most cases, therefore, the trials are unlikely to be conclusive. Larger and more powerful follow-up trials will be needed. It’s going to be expensive and time consuming.

In terms of published clinical trial data, they are scarce. The FDA recently recommended that Mesoblast stop enrolling participants in its Covid-19 trial using mesenchymal stem cells because the data was not encouraging.

Three recent reports of MSC’s randomized, double-blind, placebo-controlled trials for Covid-19 are worth seeing, but the results are mostly unclear. In one, a team from the University of Miami were very excited about their data, although further examination found that the trial was too small and the groups too unbalanced to draw firm conclusions. A somewhat larger subsequent trial in China was also inconclusive. While a third small study in Indonesia was a bit more optimistic, it’s unclear whether it was balanced or had enough power to draw any concrete conclusions.

Based on the research Mina and I conducted, these three published trials were to be among the most rigorous trials related to Covid-19 stem cells in the group. Despite this, due to various characteristics, especially their small size, they still did not provide clear signals. This doesn’t bode well for the clarity of the test scores we predicted to be less powerful in design.

Tlaunch dozens of cell therapy trials against the Covid-19 wall in hopes of seeing what, if any, sticks is riddled with issues and risks.

Resources are limited, so spending tens or hundreds of millions of dollars on mostly unpromising cell medicine trials is likely to be a waste. Additionally, participants in these trials are unlikely to be available to participate in Covid-19 trials with more promising therapies. And there is also the issue of false hopes for the participants, their families and the public more generally.

A more serious risk, but perhaps less likely, is that these approaches could harm people with Covid-19. For example, if the rationale that stem cells could treat Covid-19 by reducing the activity of the immune system has a chance to be correct, then such treatment might overtake. Stem cell therapies could reduce immunity too much, causing the virus to spread more from cell to cell, or cause other damage unexpectedly.

With so much untargeted activity already underway, at this point we can only wait and see how this cellular medicine experiment for Covid-19 will turn out. So far, over a year later, there isn’t much to be optimistic about.

Paul Knoepfler is a professor at the Davis School of Medicine at the University of California, whose research focuses on stem cells and cancer. He writes about ethics, politics and other topics on his blog, The niche.