Dataset Information

Safety, efficacy and biomarkers analysis of mesenchymal stromal cells therapy in ARDS: a systematic review and meta-analysis based on phase I and II RCTs.

ABSTRACT:

Background

Mesenchymal stromal cells (MSCs) therapy for acute respiratory distress syndrome (ARDS) is an emerging treatment, but most of the current trials of MSCs stay in the animal experimental stage, and the safety and efficacy of MSCs in clinical application are not clear. We aimed to analyze the safety, efficacy and biomarkers of mesenchymal stromal cells in the treatment of ARDS.

Methods

For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of science, CNKI, VIP and Wan Fang data, studies published between database inception and Mar 17, 2022. All randomized controlled trials (RCT) of stem cell interventions for ARDS were included, without language or date restrictions. We did separate meta-analyses for mortality, subjects with adverse events (AEs) and subjects with serious adverse events (SAEs). Since the trials data are dichotomous outcomes, the odds ratio (OR) is adopted for meta-analysis. The quality of the evidence was assessed with the Cochrane risk of bias tool.

Findings

In total, 5 trials involving 171 patients with ARDS were included in this meta-analysis. A total of 99 individuals were randomly assigned to receive MSCs treatment, and 72 were randomly assigned to receive placebo treatment. Treatment with MSCs appeared to increase the occurrence of adverse events, but this result was not statistically significant (OR, 1.58; 95%CI, 0.64-3.91; P = 0.32). The occurrence of serious adverse events was lower in the MSCs group than in the placebo group (OR, 0.57; 95%CI, 0.14-2.32; P = 0.43); there seems to be no significant difference between the two groups in terms of 28 days mortality (OR, 0.93; 95%CI, 0.45-1.89); oxygenation index and biomarkers showed a tendency to improve in treatment, but there was a lack of more statistically significant clinical evidence to support them.

Interpretation

Based on the current clinical trials, MSCs intervention has some safety for ARDS patients, but its effectiveness and predictive value of airspace biomarkers need to be determined by more large-scale, standard randomized controlled trials.

SUBMITTER: Wang J

PROVIDER: S-EPMC9233855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNo effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.MethodsThe STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.FindingsNo prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.InterpretationA single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.FundingThe National Heart, Lung, and Blood Institute.