Umbilical cord-derived mesenchymal stem cells modulate tnf and soluble tnf receptor 2 (stnfr2) in covid-19 ards patients

D. KOUROUPIS, G. LANZONI, E. LINETSKY, S. MESSINGER CAYETANO, S. WISHNEK METALONIS, C. LEÑERO, L. D. STONE, P. RUIZ, D. CORREA, C. RICORDI

Research output: Contribution to journalArticlepeer-review

Abstract

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 α and β (TNFα and TNFβ). 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 TNFα, TNFβ 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, TNFα, and TNFβ 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 TNFα and TNFβ, compared to controls. CONCLUSIONS: These observations suggest that sTNFR2 plays a mechanistic role in mediating UC-MSC effect on TNFα and TNFβ plasma levels, determining a decrease in inflammation in COVID-19 ARDS.

Original languageEnglish (US)
Pages (from-to)4435-4438
Number of pages4
JournalEuropean review for medical and pharmacological sciences
Volume25
Issue number12
DOIs
StatePublished - 2021

Keywords

  • Acute Respiratory Distress Syndrome (ARDS)
  • Anti-inflammatory effect
  • COVID-19
  • Hyperinflammatory response
  • Immunomodulation
  • Mesenchymal Stem Cells (MSC)
  • Soluble TNF Receptor 2 (sTNFR2)
  • Tumor Necrosis Factor (TNF)
  • UC-MSC
  • Umbilical Cord

ASJC Scopus subject areas

  • Pharmacology (medical)

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