Systemic Effects of Trauma and Trauma-Derived Exosomes on Bone Marrow Function

Abstract

INTRODUCTION: Severe trauma disrupts bone marrow (BM) function and is associated with persistent anemia and immunosuppression. Exosomes are extracellular vesicles that have been implicated in disease, cellular functions, and immunomodulation. The effects of trauma plasma-derived exosomes on BM hematopoiesis have not been studied; we hypothesized that trauma plasma-derived exosomes would suppress BM function. METHODS: Plasma was collected from a prospective, cohort study of trauma patients (n = 15) with hip and/or femur fractures and an Injury Severity Score greater than 15; elective total hip arthroplasty patients (n = 11) served as operative controls. Exosomes were isolated from plasma with the Invitrogen Total Exosome Isolation Kit. Healthy BM was cultured with either 2% plasma, 50 µg, 100 µg, or 200 µg of exosomal protein and BM progenitor growth (CFU-GEMM, BFU-E, and CFU-GM) assessed. Differences were compared using the Mann-Whitney t-test, with significance defined as p < 0.05 vs total hip arthroplasty. RESULTS: Trauma patients were significantly younger than total hip arthroplasty patients (mean 44 vs 61 years), with no difference in sex between groups. In vitro exposure to 2% trauma plasma significantly decreased growth of all BM progenitors (Table). In vitro exposure to 50 µg did not affect BM progenitor growth; 100 µg and 200 µg of trauma exosomal protein significantly decreased growth of BFU-E (22% and 14%) and CFU-GM (12% and 13%). Table. - Cohort CFU-GEMM (/50k Plated Cells) BFU-E (/50k Plated Cells) CFU-GM (/50k Plated Cells) 2% THA plasma 18 ± 3 39 ± 2 46 ± 5 50 µg THA exosomal protein 18 ± 3 23 ± 2 51 ± 2 100 µg THA exosomal protein 19 ± 1 22 ± 3 51 ± 5 200 µg THA exosomal protein 22 ± 2 22 ± 3 47 ± 6 2% trauma plasma 15 ± 3* 29 ± 6* 40 ± 7* 50 µg trauma exosomal Protein 17 ± 3 19 ± 4 47 ± 5 100 µg trauma exosomal protein 20 ± 3 17 ± 2* 45 ± 6* 200 µg trauma exosomal protein 22 ± 2 19 ± 1* 41 ± 4* *p < 0.05.THA, total hip arthroplasty. CONCLUSION: Both plasma and plasma-derived exosomes from trauma patients adversely affect BM function. Systemic effects of plasma-derived exosomes may contribute to altered hematopoiesis after severe trauma; further analysis of exosomal content may improve our understanding of altered BM function.