The Potential of Stem Cell Therapy for COVID-19

The approval of several COVID-19 vaccines has undoubtedly changed the fight against the pandemic. While the vaccination is in progress in multiple countries, it will take some time – months, even years – to vaccinate enough people to achieve collective immunity. Nevertheless, there are still millions of active COVID-19 cases. Out of those, tens of thousands of people are in critical conditions¹. These people (and more to come) require effective treatment, which we still lack. Could stem cell treatment be the answer against COVID-19? 

A closer look at the mechanism of action of SARS-CoV-2 shows that patients' life-threatening conditions are associated with an exaggerated immune system response. In severe COVID-19 cases, cytokines are released hyper-actively, which causes a cytokine storm leading to acute respiratory distress syndrome (ARDS). A cytokine storm is an exaggerated response of the immune system to an infection or other stimulus and manifests itself in extreme inflammation. In relation to COVID-19, it is a severe inflammation of the lung tissue in the most severe cases, as a result of which the patient's respiratory abilities are severely impaired. A cytokine storm has a rapid course and a high mortality rate, and its suppression is crucial for the survival of patients with severe COVID-19 disease². ARDS syndrome is a significant cause of fatalities in COVID-19. There is currently no specific treatment for ARDS, and pulmonary ventilation and conservative fluid management in the lungs remain the only options. However, even with pulmonary ventilation, mortality with advanced ARDS is very high, reaching approximately 40%³. 

Stem cell therapy, specifically mesenchymal stem cells (MSCs), could inhibit the immune system's exaggerated response in COVID-19 patients. Stem cells are special cells that can renew themselves and differentiate into various types of cells. MSCs are characterized by the potential for long-term self-renewal and plasticity and show a powerful anti-inflammatory effect and regulate the immune system's components. They can inhibit abnormal T cell and macrophage activation and affect their differentiation into regulatory T cells. They can also effectively inhibit the secretion of pro-inflammatory cytokines such as Il-1, TNF-α, Il-6, Il-12, and IFN-γ⁴. At the same time, they can produce Il-10, HGF, and VEGF. They alleviate the acute respiratory syndrome symptoms and prevent fibrosis and thus affect lung tissue regeneration⁵. Taken together, this type of therapy could not only inhibit the cytokine storm in COVID-19 patients but also help regenerate the damaged tissue!

The MSCs only minimally express the ACE2 or TMPRSS2 receptors used by the SARS-CoV-2 for cell entry, suggesting they are free from SARS-CoV-2 infection⁶. Nonetheless, the whole cells are not necessary for the therapeutic benefits. The mode of action of MSCs resides in the release of soluble factors – the MSCs secretome. The MSCs secretome displays multiple advantages over the conventional use of cell therapy – it lacks tumorigenicity, has lower immunogenicity, cannot transmit latent infections, and has various technological advantages (costs, manipulation, storage, and availability)⁷. These are the usual drawbacks of cell therapy that cause reluctance to their use, but it is possible to harvest the potential of stem cells for COVID-19 treatment without using the whole cells.

Numerous clinical studies have started worldwide and demonstrated that MSCs have great potential for COVID-19 patients with ARDS (read more). Preliminary data have shown that MSCs and MSC-derived secretome appears to be promising in the treatment of COVID-19⁸. However, it still requires a lot of work in standardization and optimization and long-term assessment of benefits and risks associated with stem cell therapy. Nonetheless, MSCs therapy of COVID-19 might be a beacon of hope in the fight against this pandemic. 

References

1. https://www.worldometers.info/coronavirus/
2. Ye Q., et al. The Pathogenesis and Treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020;80(6):607-613.
3. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685-1693. doi:10.1056/NEJMoa050333
4. Uccelli A, de Rosbo NK. The Immunomodulatory Function of Mesenchymal Stem Cells: Mode of Action and Pathways. Ann N Y Acad Sci. 2015;1351:114-26.
5. Wilson JG, et al. Mesenchymal Stem (Stromal) Cells for Treatment of ARDS: A Phase 1 Clinical Trial. Lancet Respir Med. 2015;3(1):24-32.
6. Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020;11(2):216-228. Published 2020 Mar 9. doi:10.14336/AD.2020.0228
7. Mahajan and S. Bhattacharyya, "A brief review on potential application of mesenchymal stem cell and secretome in combating mortality and morbidity in COVID-19 patients," Biomed. J., 2020.
8. Chouw, A., Milanda, T., Sartika, C.R. et al. Potency of Mesenchymal Stem Cell and Its Secretome in Treating COVID-19. Regen. Eng. Transl. Med. (2021). https://doi.org/10.1007/s40883-021-00202-5

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