Research on cell-based approaches for treating COVID-19 complications. 

Authors: Kate Brown, Ph.D., Scientific Director, Research and Development & Matthew Skiles, Ph.D., Scientist, Research and Development

As many are aware, the novel coronavirus disease COVID-19 is sweeping rapidly around the world. Scientists and clinicians everywhere are working as quickly as they can to understand how this new virus works and to try to find treatments and develop vaccines. There are a number of news stories about using stem cells as part of treating patients infected with COVID-19, and we want to explain the science behind this approach.

What we know about COVID-19.

Coronavirus Disease 2019 (COVID-19) is a potentially serious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus which first appeared at the end of 2019 in Wuhan Hubei province, China.¹ SARS-CoV-2 can be transmitted from person to person and has a high transmission rate. Because of this, the global spread of COVID-19 has been rapid.

People with COVID-19 can exhibit multiple symptoms, some of which include fever, sore throat, and respiratory ailment. It is thought that cells in the lungs are especially vulnerable due to the presence of a particular protein on the cell surface.² In severe cases of COVID-19, pneumonia or acute respiratory distress syndrome (ARDS) can develop, requiring intensive care. Unfortunately, these complications can sometimes be fatal.

A primary characteristic of severe cases of COVID-19 is the development of a highly inflammatory environment in the lungs leading to an overabundance of a type of protein called cytokines. These inflammatory cytokines trigger an immune response that in turn perpetuates the inflammation, resulting in tissue damage and severely impacting lung function. The overabundance of inflammatory cytokines is known as a “cytokine storm” or “cytokine cascade”, terms that are being used with more frequency in the news.

Why do scientists think stem cells might be useful?

While there are no specific treatments for COVID-19 at the moment, there is reason to test if mesenchymal stem cells (MSCs) could help mitigate the damaging inflammation associated with COVID-19 pneumonia and acute respiratory distress syndrome.  In fact, scientists have been exploring the use of stem cells in immune and respiratory conditions, both in animal and human clinical trials, for more than a decade. This is one reason scientists have been quick to turn to MSCs as a potential option for patients with severe COVID-19. MSCs have shown promising results in a number of different animal models, and from those animal studies we know that:

● MSCs are immune-privileged 

● MSCs are anti-inflammatory

● MSCs can home to sites of inflammation or injury

● Intravenously-administered MSCs often travel to and are retained in the lungs

Based on the positive results in animal and research studies, MSCs from adult tissues such as bone marrow and newborn tissues such as umbilical cord tissue and blood were already in clinical trials for the treatment of a number of lung conditions, even before the emergence of COVID-19. Examples of lung disorders with clinical trials using MSCs from a variety of tissue sources include ARDS^3,4 and inflammatory lung diseases associated with prematurity^5,6.

Can we prevent and reverse the damage caused by the inflammation?

Publications reporting on very early and small clinical trials exploring cell-based approaches to treating patients with respiratory conditions from COVID-19 are beginning to appear in the peer-reviewed scientific literature.   

A recent trial found that MSCs might help alleviate the damaging inflammation in pneumonia caused by COVID-19.  Seven patients with COVID-19 pneumonia, five of whom had severe or critically severe cases, were intravenously infused with clinical grade MSCs.  For all patients who received MSCs, respiratory symptoms subsided within several days, and most patients were negative for the COVID-19 virus within two weeks. Based on several types of measurements, the researchers found that the MSC administration corresponded with evidence of anti-inflammatory activity in the body.⁷ Similarly, a recent report outlined the case of a critically ill COVID-19 patient who received umbilical cord MSCs whose condition improved following infusion.^10,11

Testing of large-scale stem cell-based products.

In light of the therapeutic potential of MSCs, several companies have begun the process to test adult-tissue MSC products that were already in clinical trials for other conditions to see if they might be useful in treating inflammatory COVID-19 respiratory conditions.

For example, Athersys, Inc. and Mesoblast, Ltd. have cell-based products that have previously shown encouraging clinical trial results in the treatment of inflammatory respiratory conditions including ARDS.  Both companies recently announced that they are in discussions with various government and regulatory agencies to begin clinical testing of their products in patients with COVID-19.^8,9

COVID-19 is a novel disease. Its onset and spread have been sudden and there are currently no specific vaccines or drug treatment. While encouraging, it is important to note that the type of very early clinical result like we summarize here must be repeated in larger, well-controlled trials to fully understand if the approach is safe and effective. We will be here to help you stay informed on topics that are relevant to you and your family.

Conclusion

Clearly there is a great deal of interest in exploring stem cells, including newborn stem cells as described here, as a potential therapeutic option in COVID-19 respiratory conditions. Newborn stem cells may be particularly advantageous as they can be collected at birth and cryopreserved at their most pristine for future uses, some of which have yet to be discovered. It is important to note that the type of early clinical result like we summarize here must be repeated in larger, well-controlled trials to fully understand if the approach is safe and effective. Already, there are multiple clinical trials registered in China to evaluate cord tissue derived MSCs for treatment of COVID-19 respiratory complications¹⁰ and multiple groups are championing rapid exploration of cord tissue MSCs for COVID-19 patients^.10,12

It is too early to know if newborn stem cells banked today will be used as part of future treatment options for COVID-19 or similar conditions with significant complications, but there is the potential that the work we are seeing reported on today will become a part of helping patients with COVID-19.

We will be here to help you stay informed on topics that are relevant to you and your family.

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1. Munster VJ, Koopmasn M, van Doremalen N, et al. A novel coronavirus emerging in China – key questions for impact assessment. N Engl J Med. 2020;382:692-694.

2. Zhou P, Yang X-L, Wang X-G, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.

3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT01775774, Human mesenchymal stem cells for acute respiratory distress syndrome (START); 2013 Jan 25 [cited 2020 Mar 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01775774?term=MSC&cond=Acute+Respiratory+Distress+Syndrome&draw=2&rank=6

4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT03042143, Repair of acute respiratory distress syndrome by stromal cell administration (REALIST); 2017 Feb 3 [cited 2020 Mar 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT03042143?term=MSC&cond=Acute+Respiratory+Distress+Syndrome&draw=5&rank=2

5. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT02381366, Safety and efficacy of PNEUMOSTEM®️ in premature infants at high risk for bronchopulmonary dysplasia (BPD) – a US study; 2015 Mar 6 [cited 2020 Mar 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02381366?term=MSC&cond=Bronchopulmonary+Dysplasia&draw=2&rank=9

6. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 – . Identifier NCT02443961, Mesenchymal stem cell therapy for bronchopulmonary dysplasia in preterm babies; 2015 May 14 [cited 2020 Mar 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02443961?term=MSC&cond=Bronchopulmonary+Dysplasia&draw=4&rank=1

7. Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2^– mesenchymal stem cells improves the outcomes of patients with COVID-19 pneumonia. Aging and Disease. 2020;11:216-228.

8. Seekingalpha.com [Internet]. Athersys announces financial results for fourth quarter and full-year 2019. 2020 Mar 16. Available from: https://seekingalpha.com/pr/17810447-athersys-announces-financial-results-for-fourth-quarter-and-full-year-2019

9. Bioworld.com [Internet]. Australia’s Mesoblast plans to evaluate its stem cell therapy in patients infected with COVID-19. 2020 Mar 11. Available from: https://www.bioworld.com/articles/433641-australias-mesoblast-plans-to-evaluate-its-stem-cell-therapy-in-patients-infected-with-covid-19