Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

Stem Cell Research & Therapy

Research

Fatemeh Abbasi¹  Nasrin Fallah¹  Neda Jarooghi¹  Azadeh Amini¹  Abdoreza Nazari¹  Meysam Ganjibakhsh²  Hamidreza Jamaati³  Seyed-Mohammad Reza Hashemian³  Massoud Vosough⁴  Mohammad Amin Shahrbaf⁴  Morteza Zarrabi⁴  Hoda Madani⁴  Masoumeh Nouri⁴  Ensiyeh Hajizadeh-Saffar⁵  Hossein Baharvand⁶  Leila Taghiyar⁷  Faezeh Shekari⁸  Seyedeh Nafiseh Hassani⁸  Seyedeh-Esmat Hosseini⁹  Hediyeh Alemi^1,10  Rasoul Aliannejad^1,10  Naghmeh Khavandgar^1,10 

[1] Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, USA;Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran;Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Department of Developmental Biology, Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran;Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Nursing and Midwifery Care Research Center, Iran University of Medical Sciences, Tehran, Iran;Pulmonary Department, Thoracic Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;

关键词: COVID-19;    SARS-CoV-2;    Acute respiratory distress syndrome;    Cytokine release syndrome;    Mesenchymal stromal cells;    Cell therapy;    Extracellular vesicles;   

DOI  :  10.1186/s13287-023-03402-8

 received in 2022-11-19, accepted in 2023-06-15,  发布年份 2023

来源: Springer

【 摘 要 】

Background and aimsThe 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 methodsCOVID-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.ResultsA 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).ConclusionMSCs 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 4

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