# Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances

**Authors:** Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han

PMC · DOI: 10.3390/ijms27042079 · International Journal of Molecular Sciences · 2026-02-23

## TL;DR

This review explores how extracellular vesicles can serve as biomarkers for diagnosing and predicting outcomes in spinal cord injuries.

## Contribution

The paper highlights the novel use of EV-derived proteins and miRNAs as potential precision biomarkers for spinal cord injury.

## Key findings

- Extracellular vesicles carry molecular cargo reflecting injury severity and repair activity in SCI.
- EV-associated proteins and miRNAs show injury-specific signatures linked to neuronal and glial damage.
- EV-based biomarkers offer a framework for improving diagnostic and prognostic accuracy in SCI.

## Abstract

Spinal cord injury (SCI) is a devastating neurological disorder that can result in permanent disability and reduced quality of life, characterized by heterogeneous injury mechanisms and limited tools for accurate early diagnosis and prognostic stratification. The clinical course of SCI is driven not only by the initial mechanical insult but also by complex secondary injury cascades involving neuroinflammation, axonal degeneration, demyelination, and maladaptive repair responses. Current diagnostic and prognostic approaches, which rely largely on neurological examination and imaging, provide limited insight into these dynamic molecular processes. In this context, extracellular vesicles (EVs) have emerged as a biologically compelling source of biomarkers for SCI. EVs are released by neurons, glial cells, endothelial cells, and immune cells and carry molecular cargo that reflects cellular stress, injury severity, and endogenous repair activity. Increasing evidence indicates that EV-associated proteins and regulatory microRNAs (miRNAs) encode injury-specific signatures related to neuronal and glial damage, inflammatory signaling, metabolic stress, and functional recovery potential. In this review, we summarize the current knowledge on EV biology in SCI and discuss emerging evidence supporting EV-derived proteins and miRNAs as promising tools for refining diagnosis and prognosis. Our aim is not only to consolidate established findings but also to highlight EV-based molecular signatures as a developing framework for precision biomarker discovery in SCI.

## Linked entities

- **Diseases:** spinal cord injury (MONDO:0043797)

## Full-text entities

- **Genes:** CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, ARF6 (ARF GTPase 6) [NCBI Gene 382], Eno2 (enolase 2) [NCBI Gene 24334] {aka NSE, RNEN3}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, PF4 (platelet factor 4) [NCBI Gene 5196] {aka CXCL4, PF-4, SCYB4}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, HEPACAM (hepatic and glial cell adhesion molecule) [NCBI Gene 220296] {aka GlialCAM, MLC2A, MLC2B}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, ERN1 (endoplasmic reticulum to nucleus signaling 1) [NCBI Gene 2081] {aka IRE1, IRE1P, IRE1a, hIRE1p}, SEMA4D (semaphorin 4D) [NCBI Gene 10507] {aka A8, BB18, C9orf164, CD100, COLL4, GR3}, USP14 (ubiquitin specific peptidase 14) [NCBI Gene 9097] {aka TGT, Ubp6}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, AGO2 (argonaute RISC catalytic component 2) [NCBI Gene 27161] {aka CASC7, EIF2C2, LESKRES, LINC00980, PPD, Q10}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, ITGB3 (integrin subunit beta 3) [NCBI Gene 3690] {aka BDPLT16, BDPLT2, BDPLT24, CD61, FMAIT1, GP3A}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, HSPA8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 3312] {aka HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, Notch2 (notch receptor 2) [NCBI Gene 29492], IRAK1 (interleukin 1 receptor associated kinase 1) [NCBI Gene 3654] {aka IRAK, pelle}, FUT1 (fucosyltransferase 1 (H blood group)) [NCBI Gene 2523] {aka H, HH, HSC}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, NOTCH2 (notch receptor 2) [NCBI Gene 4853] {aka AGS2, HJCYS, hN2}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, VIM (vimentin) [NCBI Gene 7431], TNF receptor-associated factor 6 [NCBI Gene 222344], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, WNT10B (Wnt family member 10B) [NCBI Gene 7480] {aka SHFM6, STHAG8, WNT-12}, C1QA (complement C1q A chain) [NCBI Gene 712] {aka C1QD1}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, Wnt10b (Wnt family member 10B) [NCBI Gene 315294], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, MOG (myelin oligodendrocyte glycoprotein) [NCBI Gene 4340] {aka BTN6, BTNL11, MOGIG2, NRCLP7}, S100b (S100 calcium binding protein B) [NCBI Gene 25742] {aka S100P}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, MIR215 (microRNA 215) [NCBI Gene 406997] {aka MIRN215, miRNA215, mir-215}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, MIRLET7B (microRNA let-7b) [NCBI Gene 406884] {aka LET7B, MIRNLET7B, hsa-let-7b, let-7b}, Map2k3 (mitogen activated protein kinase kinase 3) [NCBI Gene 303200] {aka Mek3, Mkk3}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, MBP (myelin basic protein) [NCBI Gene 4155], ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354] {aka FIC, MARC, MCP-3, MCP3, NC28, SCYA6}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** inflammation (MESH:D007249), injuries (MESH:D014947), neurodegeneration (MESH:D019636), glial injury (MESH:D004194), amyotrophic lateral sclerosis (MESH:D000690), cognitive complications (MESH:D000079690), astrogliosis (MESH:D005911), fibrosis (MESH:D005355), AIS (MESH:C538175), demyelination (MESH:D003711), neurological injury (MESH:D020196), bone fractures (MESH:D050723), pain (MESH:D010146), infection (MESH:D007239), neurotoxic (MESH:D020258), coagulation (MESH:D001778), Alzheimer's disease (MESH:D000544), Impairment (MESH:D060825), permanent disability (MESH:D003638), polytrauma (MESH:D009104), cancer (MESH:D009369), ischemic damage (MESH:D017202), spinal cord ischemia (MESH:D020760), cerebral ischemia (MESH:D002545), TBI (MESH:D000070642), deep vein thrombosis (MESH:D020246), neuroinflammation (MESH:D000090862), CNS diseases (MESH:D002493), syringomyelia (MESH:D013595), hematological complications (MESH:D011250), white matter injury (MESH:D056784), EV (MESH:D004819), axonal degeneration (MESH:D009410), NP (MESH:D009437), Spinal Injury (MESH:D013124), OPC (MESH:C564935), vascular complications (MESH:D003925), functional disability (MESH:D003291), hypercoagulability (MESH:D019851), gray matter injury (MESH:D002549), ischemia (MESH:D007511), neurological disorder (MESH:D009461), immune dysregulation (OMIM:614878), Wallerian degeneration (MESH:D014855), ASIA Impairment (MESH:D006478), necrosis (MESH:D009336), neuronal cell body injury (MESH:D002280), hyperalgesia (MESH:D006930), SCI (MESH:D013119), tissue damage (MESH:D017695), fibrotic disorders (MESH:D009358), axonal damage (MESH:D001480), neurological sequelae (MESH:D009422), damage (MESH:D020263), cognitive deficits (MESH:D003072), neuronal apoptosis (MESH:D065703), axonal loss (MESH:D012183), hemolysis (MESH:D006461)
- **Chemicals:** aluminum (MESH:D000535), metal (MESH:D008670), AuNPs (-), tyramine (MESH:D014439), gold (MESH:D006046), salt (MESH:D012492), Retinoic acid (MESH:D014212), oxygen (MESH:D010100), ferrocene (MESH:C004998), graphene oxide (MESH:C000628730), polyethylene glycol (MESH:D011092), phosphatidylserine (MESH:D010718), carbon (MESH:D002244), phospholipid (MESH:D010743), ATP (MESH:D000255), luminol (MESH:D008165), luminal (MESH:D010634), Lipid (MESH:D008055), lipopolysaccharide (MESH:D008070), sphingolipids (MESH:D013107), MXenes (MESH:C000723374), Glutamate (MESH:D018698), cholesterol (MESH:D002784), Ceramides (MESH:D002518), ROS (MESH:D017382)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481)

## Full text

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## Figures

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## References

139 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940782/full.md

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Source: https://tomesphere.com/paper/PMC12940782