Encapsulated Clues: Exosomal MicroRNAs in Postmortem Body Fluids for Cause of Death Diagnosis and Postmortem Interval Estimation – A Systematic Scoping Review

Molecular markers such as exosome-associated microRNAs (miRNAs) may be stable and disease-specific in postmortem bodily fluids, which are essential because the diagnosis of sudden and unexplained deaths remains difficult in forensic practice, especially when traditional autopsy and histology yield subtle or nonspecific findings. This study aims to map and describe the use of exosomal miRNAs in postmortem bodily fluids for determining the cause of death, particularly acute myocardial infarction (AMI) and ischemic heart disease (IHD), as well as for evaluating postmortem interval (PMI) and biomarker stability. In accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews and Joanna Briggs Institute guidelines, a systematic scoping review was carried out, screening several biomedical databases for primary human autopsy studies that quantified exosome-associated miRNAs in postmortem fluids and reported cause of death, PMI, or storage conditions. Data were charted and synthesized in structured tables and narrative form. Two small autopsy case–control studies on IHD and AMI, and one methodological feasibility study, were found to be eligible. Within reasonable forensic PMIs, exosomes and their RNA cargo were recoverable and morphologically intact in plasma, serum, and pericardial fluid; experimental data supported short-term stability under a range of storage conditions. Exosomal miRNAs were found to express differently in cardiac and noncardiac deaths across studies; panels containing miR-486-5p, miR-126-3p, and others showed promising, yet still exploratory, diagnostic markers for IHD. There were no PMI prediction models created that were verified. Although small samples and methodological heterogeneity constrain the current evidence, exosomal miRNAs in postmortem bodily fluids seem to be technically doable, relatively stable, and biologically plausible candidates for supporting the cause of death diagnosis in IHD. To translate exosome-based miRNA signatures into reliable forensic tools, future research should focus on standardized preanalytical and analytical protocols, larger multicenter autopsy cohorts, strict diagnostic accuracy designs, and dedicated modeling of PMI.