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Published on: October 11, 2024
Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized
Morteza Zarrabi1, Mohammad Amin Shahrbaf1, Masoumeh Nouri1
1Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Background And Aims:
The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients.
Materials And Methods:
COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention.
Results:
A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14-1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005-1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041).
Conclusion:
MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073 .
Insights
Mesenchymal stromal cells (MSCs) and extracellular vesicles show promise in treating severe COVID-19 by reducing inflammation. This therapy demonstrated safety and efficacy in reducing inflammatory markers and potentially mortality in patients with ARDS.
Area of Science:
- Immunology
- Regenerative Medicine
- Infectious Diseases
Background:
- Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS) and multiorgan failure due to severe inflammation.
- Mesenchymal stromal cells (MSCs) and their derivatives are explored for their anti-inflammatory properties.
- Novel therapeutic strategies are needed to manage severe COVID-19 complications.
Purpose of the Study:
- To evaluate the safety and efficacy of mesenchymal stromal cells (MSCs) and their derived extracellular vesicles (EVs) in treating COVID-19 patients with ARDS.
- To assess the impact of MSCs and MSC-EVs on inflammatory markers and clinical outcomes.
- To compare the therapeutic effects of MSCs alone versus MSCs combined with EVs.
Main Methods:
- A randomized controlled trial involving COVID-19 patients with ARDS.
- Intervention groups received either MSCs alone or a combination of MSCs and MSC-derived EVs.
- Patients were monitored for clinical symptoms, laboratory parameters, and inflammatory markers.
Main Results:
- MSC therapy, particularly in combination with EVs, was associated with reduced mortality compared to the control group.
- MSC infusion significantly decreased key inflammatory cytokines, including IL-6, TNF-α, and IFN-γ, as well as C-reactive protein (CRP).
- No serious adverse events were reported with MSC or MSC-EV treatment.
Conclusions:
- Mesenchymal stromal cells and their extracellular vesicles represent a safe and effective therapeutic option for severe COVID-19.
- This stem cell-based therapy can significantly mitigate the inflammatory cascade associated with COVID-19.
- Further research and clinical application of MSCs and EVs are warranted for managing severe respiratory infections.
