Interview with Sean Morrison on cellular therapies for COVID-19

Sean Morrison M.D.
Professor Sean Morrison, Ph.D.

To get at addressing what’s the real deal on the idea of cellular therapies for COVID-19, I did a short email Q&A interview with Dr. Sean Morrison.

Sean is Chair of the Public Policy Committee at ISSCR and Director of Children’s Research Institute at UT Southwestern. He was also President of ISSCR in 2015-2016, and during his tenure I interviewed him here on The Niche about the challenges and future of the stem cell/regenerative medicine field. You can read more about the Morrison lab here.

Here’s the interview.

PK: In the big picture, can you see potential roles for cellular therapies for COVID-19? Is there something unique they might be able to achieve that other approaches like anti-viral drugs could not?

I’m afraid I’m skeptical about cellular therapies for Covid-19. Some have suggested that transplantation of immune effector cells, such as NK cells, into patients might promote a more effective immune response. I worry it will take too long for the transplanted cells to engraft and mount an effective immune response against a virus that often kills patients within days of hospitalization. Others have suggested that mesenchymal stem cell (MSC) transplants might provide a benefit by attenuating the hyper-inflammation that occurs in late stage patients. While there has been some evidence that MSCs can attenuate pathological immune responses in some contexts, most clinical trials that tested this strategy failed. The other red flag is that all of the cell therapies I have seen proposed for Covid-19 have been repurposed from very different indications. To some extent that’s to be expected when dealing with a novel pathogen. However, it gives one pause when a cell therapy under development for cancer is suddenly touted as also having anti-viral activity. Immunologically, these are two very different problems that require very different kinds of pre-clinical testing.

There are things we can do. Social distancing is already making a big difference. Second, we need a national strategy for Covid testing on a much larger scale. That is the only way to achieve the goal of getting people back to work. I would draw people’s attention to Germany, which is rolling out widespread testing for anti-coronavirus antibodies to identify people with immunity to the virus. We need to find a way to do that on a national scale in the US. Finally, therapeutic recommendations should be based on data from clinical trials, not gut feelings. It doesn’t help when untested therapies are promoted as possible cures that should be widely adopted outside of clinical trials – it diverts resources in unproductive directions and has the potential to harm people.

PK: What unique risks might cellular and regenerative medicine therapies pose in COVID-19 patients as compared to traditional pharmaceutical drugs?

The cellular therapies proposed so far have sometimes been intended to increase immune activity and sometimes to decrease immune activity. The problem is that we don’t know whether patients would benefit from increased or decreased immune activation. Maybe it depends on the stage of disease. Perhaps increased immune activation would benefit early stage patients and decreased activation would benefit late stage patients. If we guess wrong, some of these cell therapies could make things worse. We need rigorous clinical trials to test new ideas. But there also has to be a sober consideration of the strength of the science supporting new ideas and of the potential risks and benefits.

PK: There are a few dozen registered small studies and trials utilizing allogeneic MSCs for COVID-19 based on the general premise of reducing overactive immune responses and/or inflammation. More such trials are going to begin shortly. As an immunologist, what do you think of this proposed overall MSC-immunomodulatory approach?

While there has been some evidence that MSCs can attenuate pathological immune activation in some contexts, most clinical trials that tested this strategy failed. As a result, I’m skeptical that MSCs will benefit Covid-19 patients. Allogeneic MSCs are probably rapidly eliminated by a patient’s immune system, particularly in the hyper-inflammatory environment within a Covid patient. Whether or not people disagree, the key thing is that advocates for this approach should test it in regulated clinical trials and publish their results. MSCs have too often been sold directly to patients as “cures” without systematic clinical trials to test for safety and effectiveness. Nobody should represent this approach to Covid patients as a therapy that is known to be effective.

PK: Exosomes, mainly derived from MSCs, are also being tested, in some cases via IV administration but in other cases via inhalation. Thoughts on exosomes for COVID-19?

There is no reason to think that exosomes would provide any benefit to a Covid-19 patient. The scientific community is still struggling to understand precisely what exosomes are, what they do, and whether administration to a patient could have any effect. If people are able to develop well thought out scientific rationales for the use of exosomes in Covid patients, and compelling pre-clinical data, then this approach would have to be tested in regulated clinical trials. Nobody should represent this approach as a therapy that is known to be effective.

PK: Are there any new insights into why seemingly very similar patients have such extremely different experiences after infection with the novel coronavirus? Could it be the dose of exposure? Genetic factors?

We don’t know. Differences among people in pre-existing conditions certainly contribute. Genetic differences could play a role. There are all kinds of differences among individuals in their immune systems, some of which arise by chance and some of which are shaped by our prior infections/illnesses. We all have somewhat different T and B cell repertoires because the receptors that determine the specificity of these immune cells undergo random changes during development. Those random changes could make all the difference when confronting a novel pathogen. Some people may get lucky and just happen to have T cells and B cells that are good at combating this virus. Others may be unlucky. Layered on top of these differences are the effects of prior history. For example, people who received chemotherapy may have lost some of their protective immune cells. We still have a lot to learn about the biology.

The good news is that the scientific and medical communities have been mobilized. It will be incredibly inspiring over the next two years to watch as scientists dissect the biology of Covid-19 in incredible detail. There will be lots of unexpected new ideas and we will test many new potential therapies. We will ultimately develop an effective vaccine. This could be a turning point that stimulates the development of a new generation of anti-viral drugs. Physicians will figure out how to provide more effective supportive care to late stage patients. The mortality rate will decline over time. At some point we will think of Covid-19 in the same way as we used to think of other deadly viral pathogens, like polio, that were once major public health problems but that now no longer seem relevant to our daily lives.

PK: The FDA seems in a rapid-approval kind of mode for COVID-19-related investigational therapies, with some approaches and INDs being cleared in as little as a few weeks. Do you have any concerns about that or instead given the extreme risks of the pandemic do you feel such speedy approvals are sometimes going to be the way to go during the outbreak?

I have enormous respect for the FDA and the talented people who work there. Most Americans don’t understand how important the FDA is to ensure the safety and effectiveness of therapies sold to patients. In recent years, many states, and even the federal government, have passed Right-to-Try laws that were sold as a way of accelerating medical innovation and giving incurable patients wider access to experimental therapies. In fact, few patients are likely to ever benefit from these laws. The real intent of those laws was to undermine FDA regulation. I worry that the current environment may stimulate efforts by bad actors to use Right-to-Try laws as a pretext to deliver fake therapies to desperate patients.

I’m glad many organizations were able to launch clinical trials for diverse anti-viral agents so quickly during the current pandemic. The key thing is that these decisions to accelerate entry into clinical trials have to be based on credible data that provide a sound rationale for why patients might benefit. I do worry in the current environment that FDA may experience political pressure to accelerate approvals for some agents that are not supported by sound science. That would harm patients and divert resources from more promising approaches.

PK: Anything else you think important to add?

I hope this experience redoubles the nation’s commitment to science and medical research. The public strongly believes in the power of medical research but the general public doesn’t pay much attention to changes in science policy or funding. Most people rarely think about medical research. They assume it’s going on in the background and that it’ll be there to help them if they ever get really sick. But national policies that undermine medical research really do affect our ability to be there for people when they need us.

Medical researchers often find themselves defending meritorious work against restrictions that are imposed for political or ideological reasons. For example, the recent federal restrictions on fetal tissue research are already undermining work on anti-viral therapies – the same kind of research that led to the development of anti-viral vaccines and therapies that have saved millions of lives. Given the broad bipartisan support for this research over many decades it doesn’t make sense to undermine this research during a viral pandemic. I’m hopeful that the Covid experience will make people less tolerant of policies that undermine medical research. I’m hopeful that this will be a Sputnik moment for medical research, galvanizing public support for medical science and our dependence on it as a society.

23 thoughts on “Interview with Sean Morrison on cellular therapies for COVID-19”


    As mesenchymal stem cells (MSCs) are known to be immune‐privileged, safe, and able to have immunomodulatory abilities, they have been tested in limited clinical trials to treat COVID‐19 patients with pneumonia.

  2. Mr. Morrison is ignoring all the data from the most advanced cellular therapy ever to be tested on acute respiratory distress syndrome. My question to you Paul is why didn’t you ask him about it?

    Athersys has a wealth of preclinical and clinical data in ARDS using MAPCs. The most advanced is a phase two trial that met its primary endpoint of safety and showed a reduction in the number of ICU and ventilator days. The company also has pre -cinical data on a pair of cadaver lungs where one of the lungs was used as control vs. one lung that was treated. It worked. They also have a wealth of biomarker data that confirm the MOH of immunomodulation. So to paint all cellular therapies with broad brush strokes when the data is there to examine leaves your readers misinformed. To become more informed start here…. Why not take a deep dive into this data and report back to your readers?

  3. Greg Maguire, Ph.D.

    Thank you for the important discussion with Prof Dr Morrison on the use of stem cells for Covid-19. I’d like to add a couple of points. First, regarding Germany, the US population is about 4x of Germany’s (83 million). But this begs for a discussion of how to scientifically approach the Covid-19 outbreak despite large populations in both countries. Being led by a Dr of physical chemistry, Dr. Angela Markel, and where physicians in order to be entitled Doctor (M.D.), must perform research and publish that research, unlike here in the US where the M.D. memorizes scientific and medical facts but lacks training in scientific, statistical, and sampling theory methodologies, the German government along with its medical and scientific communities plans a scientific approach to randomly sample the population for Covid-19 active infections, past infection, and death rates to understand the disease. The Helmhotz Institute for Infection Research is a key player in Germany’s efforts { Prof. Dr. Morrison, Ph.D. is correct about Germany.

    A few more, of many considerations in using stem cells for Covid-19. First the stem cell type and the phenotype of that stem cell may be important in regulating the innate and adaptive immune systems, and the inflammation induced by the immune systems. Different stem cells types (bone marrow vs. adipose derived for example) and their phenotypes, differentially regulate T-cells, macrophages, and Beta-lymphocytes, for example. Cells versus exosomes may be important given that, for example, BMSC transplants induce an aged, down regulated phenotype in T cells, an adaptive immune cell important to clearing viruses. Exosomes can also be dosed in a much more precise manner than can be cells. Having excellent survival and penetration capabilities, as well as immunoprivilege for some types (ADSC exosomes, unlike BMSC exosomes, lack MHC class II proteins), and can be precisely dosed in time and space. Intranasal, ingestion (yes, some exosomes survive in low pH of the gut), IV, subque, etc. And dosing can be stopped unlike that of cell transplants where the cell may survive for long periods, doing so with a disease causing phenotype (Transplanted stem cells survive a long time: do they make you sick? Maguire G, J R Soc Med. 2019 Oct;112(10):412-414). Further, some stem cell types and their phenotypes induce a robust immune response to kill the invading pathogen, inducing much inflammation in the process. Other stem cell types are proresolving, reducing inflammation and inducing wound healing (inducing macrophages into a M2 phenotype from the M1 phenotype). Remember, much of what happens in Covid-19 is the tissue damage (fibrosis) within the cardiovascular system, including the heart itself, and the pulmonary system – and other organs too as we are beginning to discover. One can well imagine a dosing regimen where the exosomes of one cell type of a given phenotype is dosed at disease onset to fight infection, and a different type is dosed later in the sequelae of the disease to resolve inflammation and the “cytokine storm,” and repair the tissue. Some of this is explained in a recent paper (The Safe and Efficacious Use of Secretome From Fibroblasts and Adipose-derived (but not Bone Marrow-derived) Mesenchymal Stem Cells for Skin Therapeutics, Maguire G. J Clin Aesthet Dermatol. 2019 Aug;12(8):E57-E69) . All of what I’m suggesting is speculation at this point, and without good studies and careful involvement of the FDA in bringing forth these therapies, medicine will offer even more procedures and therapeutics that only do harm (Morgan DJ et al, 2019, 2019 Update on Medical Overuse: A Review, JAMA Intern Med. 2019 Sep 9. doi: 10.1001/jamainternmed.2019.3842; Smith RC (2019) Is Medicine Greedy and Morally Bereft? Psychology Today, May 5, 2019).

  4. As a matter of fact, New York State has tested about 40% more people per million population than Germany has.

  5. Currently, Germany is 25th in the world in tests per million population so I’m not sure why they are being held out as the torch bearer. The US is 40th and has administered about half as many tests per million population as Germany. That’s not the entire story though. The US is about 28 times larger than Germany. Also, the US has about 250 million more people than Germany. Both of these factors make it much more difficult to administer tests to everyone in the US. All the top countries and territories for testing have small populations and land masses. It doesn’t seem to me like Prof Morrison has thought about this much.

    1. I agree about Germany. No single reason explains Germany´s lower death rate, but extensive testing doesn´t explain it. Likelier is the stringent social distancing policy, which has been in place for over a fortnight now and is policed, is certainly a major factor. All businesses, and universities were told to send staff home, and to work there if possible, and all gathering places (cafes, restaurants, cinemas, markets, department stores, etc) were closed weeks ago.

      1. Morrison talks about widespread testing in Germany. That’s a lie. They are not even in the top 20. Also, The EU should be compared to the US, not individual countries that are a fraction of the land mass and population as the US. Switzerland is a horror show for example. NYC is a nightmare. The EU is way worse than the US.

        1. Bill can you please cite some sources for your numbers? Its fairly hard to get accurate information, so I’m curious as to how adamant you seem to be about Germany not being good? Opinions are one thing, facts are another. Also keep in mind that information shifts from time of interview and real time. Certainly Germany has been reported in the news as to being highly responsive in their testing (Bloomberg). But that was nearly a week ago. Love to hear your sources, thanks!

          As for testing/reporting not being important in stopping the spread… of course it is! Health officials have used testing for decades in helping curb the spread of all mater of infectious diseases. Its called Epidemiology, its a science!

          1. HI Matt

            “Bill can you please cite some sources for your numbers?”

   You can sort on columns. This site is updated more often than the Johns Hopkins site and has a lot more information (with citations). They cite this page for their case numbers on Germany for example: You can drill down to look at states and counties in Germany on this page.

            “I’m curious as to how adamant you seem to be about Germany not being good?”

            I don’t recall saying Germany isn’t “good”. I said that they were not even in the top 20 for testing per capita. At the time, they were 25th per capita in testing. Now, they are 30th. Is that good? bad? I don’t know. All I do know is that there were 24 other places with more testing per capita at the time I posted my comment. I think my point that the ability to test people is affected by land mass and population is accurate given the available facts.

            The Bloomberg article did cite 920K tests in Germany. The worldometers site currently has total tests in Germany at 918K, so there seems to be a bit of a disconnect there.

            “As for testing/reporting not being important in stopping the spread… of course it is! ”

            I never said that testing wasn’t important in stopping the spread and agree with you on this point.

            1. Thanks for sharing Bill.

              I wouldn’t call a 0.22% difference between Bloomberg and Worldometers a disconnect. Expecting a certain level of precision and accuracy here would be a mistake. From the WHO, to this source, or any other we can expect a certain level of error.

              My feeling is your original post was a bit hostile. Any of us will be operating off of information at the time, and looking back will always yield a different picture. You are certainly entitled to your opinion, but it is just that, and its relative. I also have to wonder why the apparent visceral reaction to Dr. Morrison’s comment. He’s an incredibly accomplished person, more than qualified for his position. Neither he, you, or I for that matter are experts here. And again, information at the time and one is aware of is changing on a daily basis, so some latitude is expected. The context of a conversation also matters. Remember, this was just a conversation for a blog… not a scientific presentation. We all make mistakes, even when we post on a blog (right?).

              As for the other comment on testing, that was meant for elsewhere in the thread. Blog etiquette can be messy sometimes.

              I appreciate the discussion!

              1. . The disconnect is because the Bloomberg data is from about a week ago and the worldometer number is supposed to be up to date. It seems to me that assuming the Bloomberg data is accurate, the number today should be higher given the number of tests per day that Germany is doing. My best guess is that the worldometer number is from around the same time as the Bloomberg article and is not up to date.

              2. Germany has updated to 1,317,887 tests, which makes more sense to me given the number a week ago. They are now 17th in tests per million population.

  6. I value concerns about unproven cellular therapies used as trial for COVID-19 but significant data now available that proved benefits to such patients. Blood transfusion was introduced during the world wars and as matter of urgency without any prejudice for proper clinical trials (now is saviour of lives) and why step mother attitude toward stem cells. Interestingly and unfortunately the stem cells scientists fraternity itself is a significant hurdle in the way of moving this stem cells field forward

    Kuldip Sidhu

    1. Hello 2154,
      The problem is there ISN’T any solid data showing real efficacy on any form of stem cells (there are many) for COVID-19. Anything is anecdotal at best, and as often cited, what looks good anectodally often fails to stand up to the rigours of a clinical trial. Organizations like ISSCR and ISCT among others aren’t hurdles at all, but promote the safe development of stem cell and other cellular based therapies. Safe being the critical term… sadly history has shown that lack of appropriate clinical testing leads to poor medicine with side effects, sickness, and death because that lack.

      Specifically there have been numerous calls for cord blood or mesenchymal stem cells to be used, but the limited data to date is not powered correctly, and fraught with problems.

      Battlefield medicine is borne of the horrors of war, and luckily blood transfusion has become safe because of clinical trials an rigorous oversight with organizations like AABB. Its great to get a battlefield transfusion in WWI… until that A+ donor is given to a B- recipient. Or the blood was not sterile. Or the blood was hemolyzed. Now we know better.

  7. Shyam Gajavelli

    There is a need to test exosomes in preclinical setting for SARSCoV2 before trials, but DOD, NIH still seeking proposals for non COVID conditions, when will the real basic take hold? Who is profiting from living in fear and doing little to get to the virus. Masks, chloroquine, MSCs to fight virus.

    1. I don’t see how exosomes make any sense, especially when given IV as the blood just dilutes them. Inhalation of exosomes at least gets them to the lungs, but there they could do more harm than good. We just don’t know. Talk about a shot in the dark.

  8. There is early preliminary data that has come out of China that intervenous umbilical cord expanded stem cells have helped patients who were dying. If done properly, this therapy has few to minimal risks. Desperate times need desperate measures. I totally disagree with this Interview.

    1. Can you give me more information on what the Chinese did? You mentioned intervenous umbilical cord expanded stem cells . I guess they incubated the cord stem cells ? I read on the internet that all those treated with SC lived.

      My idea would be to simply treat with autologous SC if cord SC works.

  9. Paul, with all respect, what does make Dr Morrison an expert in the clinical translation? The image title says he holds MD, which is not reflected in his resume. His publications are broadly indicating on basic research.
    What has made you to bring him as opinion expert?

    1. @Nathan,
      That MD was my mistake. I’ve corrected it to Ph.D.
      I value his perspectives on regenerative medicine and he also has some background in immunology.
      Do you disagree with some things he said? If so, please weigh in with your thoughts.

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