Treatment of acute respiratory distress syndrome caused by COVID-19 with human umbilical cord mesenchymal stem cells

The study aims to identify the impact of mesenchymal stem cell transplantation on the safety and clinical outcome of patients with severe COVID-19. The research focused on how lung functional status, miRNA, and cytokine levels changed following mesenchymal stem cell transplantation in patients with severe COVID-19 pneumonia and their correlation with fibrotic changes in the lung. This study involved 15 patients following conventional anti-viral treatment and 13 patients after three consecutive doses of combined treatment with MSCs transplantation. We confirmed that triple MSC transplantation in individuals with severe COVID-19 was safe and did not cause severe adverse reaction. Although the majority of parameters did not show a significant difference between MSC and the Control group after treatment, combined data still indicate cell therapy tends to reduce inflammation and benefits the patients. On the other hand, the increased plasma levels of some pro-inflammatory cytokines such as IP-10, MIP-1a, G-CSF, and IL-10 could suggest more immunomodulatory effect of MSC rather than immunosuppression in patients with ARDS caused COVID-19. To identify the genes with altered expression levels after influence of UC-MSCs, we compared the transcriptome profiles of PBMCs from ARDS patients caused by COVID-19 cultured with and without of UC-MSCs. 4172 genes were differentially expressed between UC-MSCs and Control. UC-MSCs upregulated in PBMCs the inflammatory-associated genes involved in especially in neutrophil-mediated immunity, and leukocyte migration and downregulated genes related to cell proliferation. UC-MSCs had immunomodulatory rather that imunosupression effect on PBMCs from COVID-19 patients.