How are regenerative medicine and stem cells being used in the treatment of COVID-19?

The COVID-19 pandemic triggered by SARS-CoV-2 emerged in Wuhan, China, in late 2019. This disease has spread rapidly worldwide due to its transmission by infected droplets from one infected person to another. Several studies report that this virus causes acute or chronic damage to organs, especially in the respiratory system. Mainly due to the overexpression of cytokines, severe damage to the lungs can occur after COVID-19. 12



Figure 1: The cytokine storm in severe COVID-19 patients. 1


Through its interdisciplinary approaches, regenerative medicine can treat the damage caused by this viral infection. Scientists can design drug delivery systems as well as biomaterials and other solutions to regenerate damaged organs. In vitro human lung models developed by tissue engineering are already available and can be used to study COVID-19, helping to understand the pathogenesis of the infection. 3D models of different tissue types are also very helpful to understand the impact of this disease in distinct body systems, as mentioned in our previous publication “3D models as a tool for studying COVID-19

. Stem cells have been shown to have a therapeutic effect on the management of COVID-19, and several clinical trials have been initiated. The stem cell effectiveness against this viral infection is related to preventing a cytokine storm, which can promote endogenous tissue repair of the lungs. 3 4


Figure 2: Therapeutic potential of regenerative medicine against COVID19. 5


In a pilot study conducted by Feng et al., umbilical cord-derived mesenchymal stem cells (UC-MSCs) were infused into 16 patients with COVID-19 (9 severe and 7 critically severe). The research group demonstrated that UC-MSCs could be safely administered in critically ill patients with COVID-19 pneumonia and that administration of UC-MSCs is associated with clinical benefit and changes in inflammatory and immune responses. 6 7


An alternative study addressed the safety and efficacy of bone marrow mesenchymal stem cell-derived exosomes as a treatment for severe COVID-19. During April 2020, 24 patients positive for the disease, who had severe symptoms, received the exosomes in a single hospital. A survival rate of 83% was observed. In total, 17 of 24 (71%) patients recovered, 3 of 24 (13%) patients remained critically ill although stable, and 4 of 24 (16%) patients died for reasons unrelated to treatment. Overall, after one treatment, the stem cell-derived exosomes restored oxygenation, diminished the cytokine storm, and reconstituted the patients' immunity. 8


In addition to stem cell therapy, other strategies associated with regenerative medicine, such as 3D bioprinting, will be extremely useful for treatments in a post-COVID era, replacing damaged organs and acting as a platform for drug development for the disease.



REFERENCES

1. Aydin, A. et al. Combating COVID-19 with tissue engineering: a review. Emergent Mater 1–21 (2020).

2. Tatara, A. M. Role of Tissue Engineering in COVID-19 and Future Viral Outbreaks. Tissue Eng. Part A 26, 468–474 (2020).

3. Softa, A. et al. Tissue Engineering and its Significance in Healthcare During COVID-19 Pandemic: Potential Applications and Perspectives. J. Ind. Intg. Mgmt. 06, 221–233 (2021).

4. Harikrishnan, P. & Krishnan, A. Tissue Engineering Strategies in Covid-19 Research. Trends Biomater. Artif. Organs 34, (2020).

5. Basiri, A. et al. Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises. Stem Cell Rev Rep 17, 163–175 (2021).

6. Sharma, D. & Zhao, F. Updates on clinical trials evaluating the regenerative potential of allogenic mesenchymal stem cells in COVID-19. NPJ Regen Med 6, 37 (2021).

7. Feng, Y. et al. Safety and feasibility of umbilical cord mesenchymal stem cells in patients with COVID-19 pneumonia: A pilot study. Cell Prolif. 53, e12947 (2020).

8.Sengupta, V. et al. Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. Stem Cells Dev.29, 747–754 (2020).

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