Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome

Abstract

Severe cases of COVID‐19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID‐19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo‐capillary barriers. The authors performed a systematic literature review and random‐effects meta‐analysis to determine the potential value of MSC therapy for treating COVID‐19‐infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2/FiO2 ratio, alveolo‐capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.

The Coronavirus Pandemic (SARS-CoV-2): New Problems Demand New Solutions, the Alternative of Mesenchymal (Stem) Stromal Cells

“…Also, a higher mortality in patients treated with MSC was reported, but probably due to the more severe baseline illness in this group of treatment (Matthay et al, 2019). Regarding pulmonary function, MSC therapy showed improvement in a short-term (3-5 days) evaluation (Qu et al, 2020), but one study reported no significant change (Zheng et al, 2014).…”

Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium

“…WJ-MSCs are becoming an interesting tool for allogenic transplantation in different kinds of disease, and also for COVID-19 complications [6][7][8]. Therefore, understanding the behavior of MSCs within the recipient tissues could be of great interest in assessing the safety of this kind of procedure.…”

“…The use of WJ-MSCs is emerging in allogenic transplantation for different kinds of patients, due to their immunomodulatory properties [4,5]. Interestingly, in recent months, intravenous infusion of allogenic WJ-MSCs has been successfully used for the treatment of patients with COVID-19 pneumonia [6][7][8].…”

Approaching coronavirus disease 2019: Mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2

“…In preclinical in vivo models of acute lung injury, MSCs reduced the pulmonary edema, concentrations of pro-inflammatory cytokines in the lung, and mortality rate [220,221]. Moreover, a recent review of the published results on MSC-based therapies for patients with ARDS (n = 117) has indicated lack of serious adverse events and a favorable trends in terms of improvement of pulmonary function, inflammatory parameters and mortality rate [222]. A Chinese pilot clinical trial indicated that transplantation of allogenic MSCs in 7 patients with COVID-19 pneumonia was safe and significantly improved the functional outcomes, causing a decrease of TNFα and an increase of IL10 serum levels [223].…”