Daily Ards Research Analysis
Clinical evidence for extracellular vesicles (EVs) suggests a potential mortality benefit of MSC-derived EVs in COVID-19–related acute respiratory distress syndrome (ARDS), while efficacy in wound healing remains unclear. An obstetric study found elevated FAR and APRI in intrahepatic cholestasis of pregnancy (IHCP), but FAR showed only modest discrimination for adverse neonatal outcomes and was not an independent predictor.
Summary
Clinical evidence for extracellular vesicles (EVs) suggests a potential mortality benefit of MSC-derived EVs in COVID-19–related acute respiratory distress syndrome (ARDS), while efficacy in wound healing remains unclear. An obstetric study found elevated FAR and APRI in intrahepatic cholestasis of pregnancy (IHCP), but FAR showed only modest discrimination for adverse neonatal outcomes and was not an independent predictor.
Research Themes
- Extracellular vesicles for ARDS
- Translational regenerative therapeutics
- Perinatal prognostic biomarkers
Selected Articles
1. A systematic review of published clinical studies using cell-derived extracellular vesicles: A focus on efficacy in COVID-19 and wound healing.
This systematic review with an individual patient data meta-analysis indicates that MSC-derived EVs may reduce mortality in COVID-19/ARDS (OR 0.46, 95% CI 0.26–0.81), while overall study heterogeneity and limited controlled trials temper confidence. Safety appears acceptable but is not definitive due to incomplete adverse event reporting.
Impact: Provides the first consolidated clinical signal that MSC-EVs may improve survival in COVID-19/ARDS and maps design and manufacturing gaps limiting translation.
Clinical Implications: EV therapy should remain within clinical trials; pending standardized manufacturing and rigorous RCTs, MSC-EVs may become adjunctive therapy for ARDS if efficacy and safety are confirmed.
Key Findings
- Included 25 clinical trials; COVID-19/ARDS was the most frequent indication (n=8, 32%).
- MSC-derived EVs dominated (20 studies, 80%); 494 patients received MSC-EVs.
- IPD meta-analysis of controlled COVID-19/ARDS MSC-EV trials (n=3; 5 arms) showed mortality OR 0.46 (95% CI 0.26–0.81; p=0.0073).
- Safety reporting was incomplete; only one serious adverse event explicitly reported.
Methodological Strengths
- Systematic search spanning 1946–2024 with predefined data extraction.
- Inclusion of an IPD meta-analysis for controlled COVID-19/ARDS trials.
Limitations
- Marked heterogeneity across trials and only 7 controlled studies overall.
- Incomplete adverse event reporting and potential publication bias.
Future Directions: Conduct multi-center, adequately powered RCTs specifying EV source (e.g., MSC), dose, route, timing, and standardized product characterization and safety reporting.
2. A systematic review of published clinical studies using cell-derived extracellular vesicles: A focus on efficacy in COVID-19 and wound healing.
In the wound healing subset, no controlled studies of MSC-EVs were available and two controlled studies of non-MSC EVs showed no clear benefit, underscoring uncertainty of efficacy. EV administration appeared generally tolerable, but incomplete adverse event reporting precludes firm safety conclusions.
Impact: Clarifies that current clinical evidence does not yet support EVs for wound healing and highlights methodological heterogeneity impeding translation.
Clinical Implications: EVs should not be adopted for wound healing outside trials; standardization of EV sourcing, isolation, dosing, and endpoints is essential before clinical use.
Key Findings
- Wound healing comprised 5 of 25 trials (20%), with no controlled studies of MSC-EVs.
- Two controlled studies of non-MSC EVs in wound healing reported no clear efficacy.
- Ultracentrifugation was the primary isolation method in 68% of trials, reflecting methodological heterogeneity.
- Safety reporting was often incomplete, limiting risk assessment.
Methodological Strengths
- Comprehensive landscape mapping across indications including wound healing.
- Transparent capture of EV isolation and characterization methods.
Limitations
- No controlled MSC-EV trials in wound healing; small and heterogeneous studies.
- Outcome measures and safety reporting were not standardized.
Future Directions: Develop consensus standards for EV production and reporting; initiate randomized, controlled wound healing trials with mechanistic endpoints and long-term follow-up.
3. Association between FAR, PAR, APRI and adverse neonatal outcomes in pregnancies complicated by intrahepatic cholestasis.
In IHCP, FAR and APRI were elevated relative to controls, but only FAR was associated with adverse neonatal outcomes and showed limited discrimination (AUC 0.607) and no independent predictive value. These biomarkers should not be used as standalone predictors.
Impact: Provides negative yet informative evidence on the limited prognostic utility of readily available inflammatory ratios in IHCP, guiding biomarker development.
Clinical Implications: Do not rely on FAR, PAR, or APRI alone to risk-stratify IHCP pregnancies; integrate with bile acids, clinical factors, and fetal monitoring.
Key Findings
- Retrospective comparative study of 165 IHCP and 155 matched controls at a tertiary center.
- FAR and APRI were significantly higher in IHCP vs controls (p<0.05).
- Among adverse neonatal outcomes, only FAR was elevated (p=0.015).
- FAR had limited discrimination (AUC 0.607; sensitivity 58%; specificity 63%) and was not an independent predictor.
Methodological Strengths
- Age and gestational age-matched control group with multivariable logistic regression.
- Use of ROC analysis to quantify discrimination.
Limitations
- Single-center retrospective design with modest sample size.
- Composite outcome and potential residual confounding.
Future Directions: Prospective multi-center studies integrating FAR with bile acids and other biomarkers to build robust predictive models for IHCP neonatal outcomes.