Extracellular Vesicles As an Emerging Frontier in Spinal Cord Injury Pathobiology and Therapy

Overview

Journal Trends Neurosci

Specialty Neurology

Date 2021 Feb 14

PMID 33581883

Citations 54

Authors

Dipankar Dutta

Niaz Khan

Junfang Wu

Steven M Jay

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are membrane-delimited particles that are secreted by nearly all cell types. EVs mediate crucial physiological functions and pathophysiological processes in the CNS. As carriers of diverse bioactive cargoes (e.g., proteins, lipids, and nucleic acids) that can be modified in response to external stimuli, EVs have emerged as pathological mediators following neurotrauma such as spinal cord injury (SCI). We discuss the roles of endogenous EVs in the CNS as well as crosstalk with peripheral EVs in relation to neurotrauma, with a particular focus on SCI. We then summarize the status of EV-based therapeutic advances in preclinical animal models for these conditions. Finally, we discuss new bioengineering strategies that are poised to enhance CNS-specific therapeutic capabilities of EVs.

Citing Articles

Decellularized tissue matrices hydrogels functionalized with extracellular vesicles promote macrophage reprogramming and neural stem cell differentiation for spinal cord injury repair.

Deng M, Xie P, Xue H, Chen Q, Zhou Y, Ming J J Nanobiotechnology. 2025; 23(1):139.

PMID: 40001048 PMC: 11853540. DOI: 10.1186/s12951-025-03152-0.

Extracellular vesicles epitopes as potential biomarker candidates in patients with traumatic spinal cord injury.

Horauf J, Schindler C, Schaible I, Wang M, Weber B, El Saman A Front Immunol. 2024; 15:1478786.

PMID: 39703513 PMC: 11656158. DOI: 10.3389/fimmu.2024.1478786.

Extracellular vesicles: biological mechanisms and emerging therapeutic opportunities in neurodegenerative diseases.

Wang L, Zhang X, Yang Z, Wang B, Gong H, Zhang K Transl Neurodegener. 2024; 13(1):60.

PMID: 39643909 PMC: 11622582. DOI: 10.1186/s40035-024-00453-6.

Acid-sensing ion channel-1 contributes to the failure of myelin sheath regeneration following spinal cord injury by transcellular delivery of PGE2.

Wu Z, Han T, Dong Y, Ying W, Fang H, Liu Y Cell Mol Biol Lett. 2024; 29(1):149.

PMID: 39627718 PMC: 11616324. DOI: 10.1186/s11658-024-00672-9.

Exosomes as promising bioactive materials in the treatment of spinal cord injury.

Li Y, Luo W, Meng C, Shi K, Gu R, Cui S Stem Cell Res Ther. 2024; 15(1):335.

PMID: 39334506 PMC: 11438208. DOI: 10.1186/s13287-024-03952-5.

References

Chaudhuri A, Dastgheyb R, Yoo S, Trout A, Talbot Jr C, Hao H . TNFα and IL-1β modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis. 2018; 9(3):363. PMC: 5838212. DOI: 10.1038/s41419-018-0369-4. View

Shin J, Goo H, Yu S, Kim D, Yoon S . Depression and Quality of Life in Patients within the First 6 Months after the Spinal Cord Injury. Ann Rehabil Med. 2012; 36(1):119-25. PMC: 3309324. DOI: 10.5535/arm.2012.36.1.119. View

Holm M, Kaiser J, Schwab M . Extracellular Vesicles: Multimodal Envoys in Neural Maintenance and Repair. Trends Neurosci. 2018; 41(6):360-372. DOI: 10.1016/j.tins.2018.03.006. View

Goncalves M, Wu Y, Clarke E, Grist J, Hobbs C, Trigo D . Regulation of Myelination by Exosome Associated Retinoic Acid Release from NG2-Positive Cells. J Neurosci. 2019; 39(16):3013-3027. PMC: 6468108. DOI: 10.1523/JNEUROSCI.2922-18.2019. View

Caruso Bavisotto C, Scalia F, Marino Gammazza A, Carlisi D, Bucchieri F, de Macario E . Extracellular Vesicle-Mediated Cell⁻Cell Communication in the Nervous System: Focus on Neurological Diseases. Int J Mol Sci. 2019; 20(2). PMC: 6359416. DOI: 10.3390/ijms20020434. View

Ramirez S, Andrews A, Paul D, Pachter J . Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers. Fluids Barriers CNS. 2018; 15(1):19. PMC: 6026502. DOI: 10.1186/s12987-018-0104-7. View

Guitart K, Loers G, Buck F, Bork U, Schachner M, Kleene R . Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia. 2016; 64(6):896-910. DOI: 10.1002/glia.22963. View

Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs R, Morozoff C, Kutz M, Huynh C . US County-Level Trends in Mortality Rates for Major Causes of Death, 1980-2014. JAMA. 2016; 316(22):2385-2401. PMC: 5576343. DOI: 10.1001/jama.2016.13645. View

Hazelton I, Yates A, Dale A, Roodselaar J, Akbar N, Ruitenberg M . Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles. J Neurotrauma. 2017; 35(4):639-651. DOI: 10.1089/neu.2017.5049. View

10.

Ciregia F, Urbani A, Palmisano G . Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases. Front Mol Neurosci. 2017; 10:276. PMC: 5583211. DOI: 10.3389/fnmol.2017.00276. View

11.

Ridder K, Keller S, Dams M, Rupp A, Schlaudraff J, Del Turco D . Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol. 2014; 12(6):e1001874. PMC: 4043485. DOI: 10.1371/journal.pbio.1001874. View

12.

Veneruso V, Rossi F, Villella A, Bena A, Forloni G, Veglianese P . Stem cell paracrine effect and delivery strategies for spinal cord injury regeneration. J Control Release. 2019; 300:141-153. DOI: 10.1016/j.jconrel.2019.02.038. View

13.

Yasui H, Donahue D, Walsh M, Castellino F, Ploplis V . Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury. Am J Physiol Lung Cell Mol Physiol. 2016; 311(1):L74-86. PMC: 4967191. DOI: 10.1152/ajplung.00429.2015. View

14.

Budnik V, Ruiz-Canada C, Wendler F . Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci. 2016; 17(3):160-72. PMC: 4989863. DOI: 10.1038/nrn.2015.29. View

15.

Sachdeva R, Gao F, Chan C, Krassioukov A . Cognitive function after spinal cord injury: A systematic review. Neurology. 2018; 91(13):611-621. PMC: 6161545. DOI: 10.1212/WNL.0000000000006244. View

16.

Branscome H, Paul S, Khatkar P, Kim Y, Barclay R, Pinto D . Stem Cell Extracellular Vesicles and their Potential to Contribute to the Repair of Damaged CNS Cells. J Neuroimmune Pharmacol. 2019; 15(3):520-537. PMC: 6981004. DOI: 10.1007/s11481-019-09865-y. View

17.

Li J, Wang B, Kodali M, Chen C, Kim E, Patters B . In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflammation. 2018; 15(1):8. PMC: 5759808. DOI: 10.1186/s12974-017-1038-8. View

18.

Sutaria D, Jiang J, Elgamal O, Pomeroy S, Badawi M, Zhu X . Low active loading of cargo into engineered extracellular vesicles results in inefficient miRNA mimic delivery. J Extracell Vesicles. 2017; 6(1):1333882. PMC: 5505005. DOI: 10.1080/20013078.2017.1333882. View

19.

Rong Y, Liu W, Wang J, Fan J, Luo Y, Li L . Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy. Cell Death Dis. 2019; 10(5):340. PMC: 6472377. DOI: 10.1038/s41419-019-1571-8. View

20.

Yang Y, Ye Y, Kong C, Su X, Zhang X, Bai W . MiR-124 Enriched Exosomes Promoted the M2 Polarization of Microglia and Enhanced Hippocampus Neurogenesis After Traumatic Brain Injury by Inhibiting TLR4 Pathway. Neurochem Res. 2019; 44(4):811-828. DOI: 10.1007/s11064-018-02714-z. View