Journal
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Volume 25, Issue 12, Pages 4435-4438Publisher
VERDUCI PUBLISHER
DOI: 10.26355/eurrev_202106_26156
Keywords
Mesenchymal Stem Cells (MSC); Tumor Necrosis Factor (TNF); soluble TNF Receptor 2 (sTNFR2); COVID-19; Acute Respiratory Distress Syndrome (ARDS); Anti-inflammatory effect; Hyperinflammatory response; Immunomodulation; Umbilical Cord; UGMSC
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Funding
- North America's Building Trades Unions (NABTU)
- The Cure Alliance
- Diabetes Research Institute Foundation (DRIF)
- Barilla Group and Family
- Fondazione Silvio Tronchetti Provera
- Simkins Family Foundation
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This study aimed to elucidate the therapeutic effect mechanism of Umbilical Cord Mesenchymal Stem Cells (UCMSC) in patients with COVID-19 Acute Respiratory Distress Syndrome (ARDS). Results showed that UCMSC treatment led to significantly increased levels of plasma sTNFR2 and decreased levels of TNF alpha and TNF beta, indicating a decrease in inflammation in COVID-19 ARDS.
OBJECTIVE: We aimed at explaining the mechanism of therapeutic effect of Umbilical Cord Mesenchymal Stem Cells (UCMSC) in subjects with COVID-19 Acute Respiratory Distress Syndrome (ARDS). Patients with COVID-19 ARDS present with a hyperinflammatory response characterized by high levels of circulating pro-inflammatory mediators, including tumor necrosis factor alpha and beta (TNF alpha and TNFB). Inflammatory functions of these TNFs can be inhibited by soluble TNF Receptor 2 (sTNFR2). In patients with COVID-19 ARDS, UCMSC appear to impart a robust anti-inflammatory effect, and treatment is associated with remarkable clinical improvements. We investigated the levels of TNF alpha, INF beta and sTNFR2 in blood plasma samples collected from subjects with COVID-19 ARDS enrolled in our trial of UCMSC treatment. PATIENTS AND METHODS: We analyzed plasma samples from subjects with COVID-19 ARDS (n=24) enrolled in a Phase 1/2a randomized controlled trial of UC-MSC treatment. Plasma samples were obtained at Day 0 (baseline, before UC-MSC or control infusion), and Day 6 post infusion. Plasma concentrations of sTNFR2, TNF alpha, and TNF beta were evaluated using a quantitative multiplex protein array. RESULTS: Our data indicate that at Day 6 after infusion, UC-MSC recipients develop significantly increased levels of plasma sTNFR2 and significantly decreased levels of TNF alpha and TNF beta, compared to controls. CONCLUSIONS: These observations suggest that sTNFR2 plays a mechanistic role in mediating UC-MSC effect on TNF alpha and TNF beta plasma levels, determining a decrease in inflammation in COVID-19 ARDS.
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