Everyone is aware of the coronavirus disease COVID-19 sweeping rapidly around the world. Scientists and clinicians everywhere are working tirelessly to try to understand just how this new virus works and to try to find treatments and develop vaccines. You may have seen 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 today.
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. 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.
Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. Older people and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness. 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.
Studies in mice have demonstrated that the anti-inflammatory effects of MSCs and their ability to reduce virus-induced lung injury and mortality. The use of MSCs in these studies have helped to effectively reduce the levels inflammation as well as the number of inflammatory cells that enter the lungs after contracting a disease such as pneumonia, which may be beneficial in COVID-19 cases.
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
19 new clinical studies have emerged on clinicaltrials.gov, which are investigating the potential use of umbilical cord stem cells in the treatment of patients infected with the new COVID-19 virus.
These studies are part of a larger effort of more than 569 new clinical trials which are trying to tackle the fast-spreading virus. These studies are primarily focused on the use of mesenchymal stem cells (MSCs) in the treatment of the disease.
Examples of lung disorders with clinical trials using MSCs from a variety of tissue sources include ARDS3,4 and inflammatory lung diseases associated with prematurity5,6.
Can we reverse the damage caused by the inflammation?
There have been many research studies investigating the uses of stem cells in reducing inflammation in respiratory disorders before COVID-19, such as Cystic Fibrosis. Currently, 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.
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 complications and multiple groups are championing rapid exploration of cord tissue MSCs for COVID-19 patients.
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.
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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.