Trauma-induced alterations in bone marrow exosome microRNA profiles

Severe trauma disrupts bone marrow function, triggering physiological changes that impair hematopoiesis, immune cell production, and the bone marrow microenvironment. Bone marrow-derived exosomes play a critical role in intercellular communication, but their contribution to the cellular response to injury remains poorly understood. This study investigates bone marrow exosome microRNA (miRNA) expression in rodents subjected to polytrauma (PT) with and without chronic stress exposure, a model simulating chronic critical illness following injury.

Bone marrow was collected from rats (n = 12/group) subjected to PT, including lung contusion, hemorrhagic shock, cecal ligation, and pseudofracture. A second group underwent PT with daily restraint stress to model chronic critical illness. Bone marrow-derived exosomes were isolated 7 days postinjury, and miRNA expression was quantified using ROSALIND Bioinformatics Software (Healthcare Technology Systems, San Diego, CA) with significance defined as p < 0.05.

Both PT and PT with daily restraint stress significantly altered the bone marrow-derived exosome miRNA cargo. Following PT, several miRNAs associated with inflammation, apoptosis, and progenitor cell regulation (miR-216b, miR-1929, miR-3472) were upregulated, and key miRNAs involved in hematopoietic stem/progenitor growth maintenance (let-7c, miR-21, miR-126b-3p) were significantly downregulated. The addition of chronic stress after PT further amplified these changes, with upregulation of pro-inflammatory and immune-regulatory miRNAs (miR-146b, miR-1940, miR-875-3p) and further suppression of miRNAs critical for erythropoiesis and regeneration (miR-144, miR-125b-5p, let-7a).

Chronic critical illness following severe trauma alters bone marrow exosome miRNA profiles, modulating gene regulatory mechanisms involved in injury response, inflammation, and recovery. These patterns suggest that chronic stress exacerbates trauma-induced bone marrow dysfunction by disrupting hematopoietic stem/progenitor growth maintenance, lineage specification, and tissue repair signaling.