Since the emergence of the novel coronavirus infection, COVID-19, researchers have been looking for a treatment to stop the devastating pandemic. During these efforts, mesenchymal stem cells (MSCs) have shown potential as the next generation of therapeutic methods with wide application for diseases that have successfully controlled “cytokine storm” following the virus infection.
In December 2019, SARS-CoV-2, the agent that causes COVID-19, was recognized in Wuhan city and turned into a pandemic with worldwide consequences. The danger of producing severe acute respiratory syndrome in many people infected with the highly contagious virus resulted in activity restrictions, economic recession, and the collapse of the health care systems around the world.
Scientists have observed that the primary mechanism of stem cell efficacy for COVID-19 treatment is managing the cytokine storm through their paracrine effects. These have raised the question about how stem cell-derived exosomes can be introduced as an alternative to stem cells, considering their ability to manage cytokine storms and not stem cell-related problems.
Exosomes are small vesicles of 30 to 130 nm size that are rich in proteins. The content of exosomes depends on the parent cell from which they are secreted. They also carry biological membrane proteins, cytosolic proteins, transcription factors, messenger RNA (mRNA), and cell adhesion molecules to help bind to target cells.
Research has shown that exosomes are as effective as MSCs in the management of “cytokine storm” so that in a pattern similar to MSCs, exosomes downregulate T-cells proliferation, induce auto-reactive lymphocytes for the apoptosis of activated T cells, and secrete anti-inflammatory cytokines such as IL-10 and TGF-β
The source of MSC-derived exosomes is a determining factor in its therapeutic effect. In many studies, bone marrow has been the primary source of MSC-derived exosomes, while umbilical cord MSCs have been used for exosome extraction in a study.
Since the onset of the pandemic, one research group has completed the study of the safety and effectiveness of intravenous delivery of MSC-derived exosome administration to COVID-19 patients.
The safety of the exosome was confirmed after observing no adverse effect within 72 h of injection. Results showed an increased neutrophil and lymphocyte count and reduced C-reactive protein, ferritin, and D-dimer, representing effective cytokine storm regulation via exosomes.
Improved clinical status evidenced by a 192% increase in the average pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/ FiO2) showed the effectiveness of the therapy.
Furthermore, the administration of exosomes in combination with antiviral drugs represents a novel intervention for treating diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents.
Nasim Kiaie, et al. Mesenchymal Stem Cell-Derived Exosomes for COVID-19 Therapy, Preclinical and Clinical Evidence. International Journal of Stem Cells Vol. 14, No. 3, 2021 https://doi.org/10.15283/ijsc20182.