Dental Stem Cell-derived Extracellular Vesicles Transfer MiR-330-5p to Treat Traumatic Brain Injury by Regulating Microglia Polarization

Overview

Journal Int J Oral Sci

Date 2022 Sep 6

PMID 36064768

Authors

Ye Li

Meng Sun

Xinxin Wang

Xiaoyu Cao

Na Li

Dandan Pei

Ang Li

Affiliations

Soon will be listed here.

Abstract

Traumatic brain injury (TBI) contributes to the key causative elements of neurological deficits. However, no effective therapeutics have been developed yet. In our previous work, extracellular vesicles (EVs) secreted by stem cells from human exfoliated deciduous teeth (SHED) offered new insights as potential strategies for functional recovery of TBI. The current study aims to elucidate the mechanism of action, providing novel therapeutic targets for future clinical interventions. With the miRNA array performed and Real-time PCR validated, we revealed the crucial function of miR-330-5p transferred by SHED-derived EVs (SHED-EVs) in regulating microglia, the critical immune modulator in central nervous system. MiR-330-5p targeted Ehmt2 and mediated the transcription of CXCL14 to promote M2 microglia polarization and inhibit M1 polarization. Identified in our in vivo data, SHED-EVs and their effector miR-330-5p alleviated the secretion of inflammatory cytokines and resumed the motor functional recovery of TBI rats. In summary, by transferring miR-330-5p, SHED-EVs favored anti-inflammatory microglia polarization through Ehmt2 mediated CXCL14 transcription in treating traumatic brain injury.

Citing Articles

Advances in the research of immunomodulatory mechanism of mesenchymal stromal/stem cells on periodontal tissue regeneration.

Zhao D, Yang R, Wei H, Yang K, Yang Y, Wang N Front Immunol. 2025; 15():1449411.

PMID: 39830512 PMC: 11739081. DOI: 10.3389/fimmu.2024.1449411.

mir-330-5p from mesenchymal stem cell-derived exosomes targets SETD7 to reduce inflammation in rats with cerebral ischemia-reperfusion injury.

Liu W, Shen Y, Pan R, Qi X J Mol Histol. 2024; 56(1):63.

PMID: 39738925 DOI: 10.1007/s10735-024-10347-6.

The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage.

Rostami M, Farahani P, Esmaelian S, Bahman Z, Hussein A, A Alrikabi H Stem Cell Rev Rep. 2024; 20(8):2062-2103.

PMID: 39150646 DOI: 10.1007/s12015-024-10770-y.

The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Fu J, Li W, Mao T, Chen Z, Lai L, Lin J Front Mol Biosci. 2024; 11:1363838.

PMID: 38741719 PMC: 11089131. DOI: 10.3389/fmolb.2024.1363838.

Unraveling the Emerging Niche Role of Extracellular Vesicles (EVs) in Traumatic Brain Injury (TBI).

Ashique S, Pal R, Sharma H, Mishra N, Garg A CNS Neurol Disord Drug Targets. 2024; 23(11):1357-1370.

PMID: 38351688 DOI: 10.2174/0118715273288155240201065041.

References

Foldes A, Kadar K, Keremi B, Zsembery A, Gyires K, Zadori Z . Mesenchymal Stem Cells of Dental Origin-Their Potential for Antiinflammatory and Regenerative Actions in Brain and Gut Damage. Curr Neuropharmacol. 2016; 14(8):914-934. PMC: 5333580. DOI: 10.2174/1570159x14666160121115210. View

Yu X, Odenthal M, Fries J . Exosomes as miRNA Carriers: Formation-Function-Future. Int J Mol Sci. 2016; 17(12). PMC: 5187828. DOI: 10.3390/ijms17122028. View

Zheng Y, Liu A, Wang Z, Cao Q, Wang W, Lin L . Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer's disease. Brain. 2019; 142(3):787-807. PMC: 6391616. DOI: 10.1093/brain/awy354. View

Mollayeva T, Mollayeva S, Colantonio A . Traumatic brain injury: sex, gender and intersecting vulnerabilities. Nat Rev Neurol. 2018; 14(12):711-722. DOI: 10.1038/s41582-018-0091-y. View

Zhu Y, Zhang P, Gu R, Liu Y, Zhou Y . Origin and Clinical Applications of Neural Crest-Derived Dental Stem Cells. Chin J Dent Res. 2018; 21(2):89-100. DOI: 10.3290/j.cjdr.a40435. View

Huising M, van der Meulen T, Flik G, Verburg-van Kemenade B . Three novel carp CXC chemokines are expressed early in ontogeny and at nonimmune sites. Eur J Biochem. 2004; 271(20):4094-106. DOI: 10.1111/j.1432-1033.2004.04347.x. View

Hayakawa K, Wang X, Lo E . CD200 increases alternatively activated macrophages through cAMP-response element binding protein - C/EBP-beta signaling. J Neurochem. 2015; 136(5):900-6. PMC: 4755817. DOI: 10.1111/jnc.13492. View

Luzuriaga J, Polo Y, Pastor-Alonso O, Pardo-Rodriguez B, Larranaga A, Unda F . Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies. Int J Mol Sci. 2021; 22(7). PMC: 8036729. DOI: 10.3390/ijms22073546. View

Lu H, Wu L, Liu L, Ruan Q, Zhang X, Hong W . Quercetin ameliorates kidney injury and fibrosis by modulating M1/M2 macrophage polarization. Biochem Pharmacol. 2018; 154:203-212. DOI: 10.1016/j.bcp.2018.05.007. View

10.

Zhang J, Li S, Li L, Li M, Guo C, Yao J . Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics. 2015; 13(1):17-24. PMC: 4411500. DOI: 10.1016/j.gpb.2015.02.001. View

11.

Khellaf A, Khan D, Helmy A . Recent advances in traumatic brain injury. J Neurol. 2019; 266(11):2878-2889. PMC: 6803592. DOI: 10.1007/s00415-019-09541-4. View

12.

Karve I, Taylor J, Crack P . The contribution of astrocytes and microglia to traumatic brain injury. Br J Pharmacol. 2015; 173(4):692-702. PMC: 4742296. DOI: 10.1111/bph.13125. View

13.

Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P . Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. Int J Nanomedicine. 2020; 15:6917-6934. PMC: 7519827. DOI: 10.2147/IJN.S264498. View

14.

Lin Y, Zhao J, Zheng Q, Jiang X, Tian J, Liang S . Notch Signaling Modulates Macrophage Polarization and Phagocytosis Through Direct Suppression of Signal Regulatory Protein α Expression. Front Immunol. 2018; 9:1744. PMC: 6077186. DOI: 10.3389/fimmu.2018.01744. View

15.

Hu X, Leak R, Shi Y, Suenaga J, Gao Y, Zheng P . Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol. 2014; 11(1):56-64. PMC: 4395497. DOI: 10.1038/nrneurol.2014.207. View

16.

Eissenberg J, Elgin S . HP1a: a structural chromosomal protein regulating transcription. Trends Genet. 2014; 30(3):103-10. PMC: 3991861. DOI: 10.1016/j.tig.2014.01.002. View

17.

Galgano M, Toshkezi G, Qiu X, Russell T, Chin L, Zhao L . Traumatic Brain Injury: Current Treatment Strategies and Future Endeavors. Cell Transplant. 2017; 26(7):1118-1130. PMC: 5657730. DOI: 10.1177/0963689717714102. View

18.

Li Z, Li Y, Jiao J . Neural progenitor cells mediated by H2A.Z.2 regulate microglial development via Cxcl14 in the embryonic brain. Proc Natl Acad Sci U S A. 2019; 116(48):24122-24132. PMC: 6883828. DOI: 10.1073/pnas.1913978116. View

19.

van Niel G, DAngelo G, Raposo G . Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018; 19(4):213-228. DOI: 10.1038/nrm.2017.125. View

20.

Rostene W, Guyon A, Kular L, Godefroy D, Barbieri F, Bajetto A . Chemokines and chemokine receptors: new actors in neuroendocrine regulations. Front Neuroendocrinol. 2010; 32(1):10-24. DOI: 10.1016/j.yfrne.2010.07.001. View