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Updated: Jun 16, 2026
Isolating, Sequencing and Analyzing Extracellular MicroRNAs from Human Mesenchymal Stem Cells
Published on: March 8, 2019
Dissecting bone marrow and plasma exosomal microRNA profiles following trauma
Agneta Peethala1, Athina L Yoham1, Letitia E Bible2
1Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida College of Medicine, Gainesville, FL.
Background:
Bone marrow dysfunction is a key driver of persistent hematologic and immune derangements following severe trauma. Circulating exosomes offer a minimally invasive platform to interrogate systemic stress responses, yet it remains unclear whether plasma-derived exosomal microRNAs reflect bone marrow regulatory programs. We hypothesized that chronic stress after polytrauma induces compartment-specific exosomal microRNA signatures.
Methods:
Male rats (N = 4/group) underwent polytrauma (lung contusion, hemorrhagic shock, cecal ligation, and pseudofracture) or polytrauma plus daily restraint stress for 7 days to model chronic critical illness. On day 7, bone marrow and plasma exosomes were isolated and profiled by small RNA sequencing. Differential expression was defined as fold change ≥1.5 or ≤-1.5 with P ≤ .05.
Results:
Chronic stress induced distinct microRNA responses in bone marrow and plasma exosomes. Only 9 microRNAs were significantly altered in bone marrow-derived exosomes following polytrauma plus daily restraint stress compared with polytrauma alone, whereas plasma-derived exosomes demonstrated 20 differentially expressed microRNAs. Overlap between compartments was minimal, indicating divergent regulatory programs. Plasma exosomal microRNAs demonstrated broader shifts consistent with systemic inflammatory and metabolic stress signaling, whereas bone marrow exosomal changes were more restricted, suggesting localized modulation of hematopoietic and microenvironmental pathways.
Conclusion:
Chronic stress following polytrauma produces compartment-specific exosomal microRNA remodeling, with plasma exosomes capturing systemic stress signatures and bone marrow exosomes reflecting localized regulatory adaptation. These findings challenge the assumption that circulating exosomes directly mirror bone marrow dysfunction and highlight the importance of tissue origin when developing exosomal microRNA biomarkers or therapeutic targets in trauma-induced chronic critical illness.
