Mesenchymal Stem Cell-Derived Exosomal MiRNAs Promote M2 Macrophages Polarization: Therapeutic Opportunities for Spinal Cord Injury

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2022 Jul 29

PMID 35903172

Authors

Ze-Yan Liang

Xiong-Jie Xu

Jian Rao

Zhe-Lun Yang

Chun-Hua Wang

Chun-Mei Chen

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) is an enormous public health concern affecting approximately 250,000-500,000 people worldwide each year. It is mostly irreversible considering the limitations of currently available treatments, and its prevention and management have been the prime focus of many studies. Mesenchymal stem cell (MSC) transplantation is one of the most promising treatments for SCI. The role of MSCs in SCI has been studied extensively, and MSCs have been shown to have many limitations. Moreover, the therapeutic effects of MSCs are more likely related to paracrine effects. In SCIs, macrophages from peripheral sources differentiate into M1 macrophages, promoting inflammation and aggravating neuronal damage; however, studies have shown that MSC-derived exosomes can induce the polarization of macrophages from the M1 to the M2 phenotype, thereby promoting nerve function recovery in patients with SCI. In this review, we discussed the research progress of MSC-derived exosomal miRNAs in promoting M2 macrophage differentiation in the SCI, and introduced some exosomal miRNAs that can regulate the differentiation of M2 macrophages in non-SCI; it is hoped that the regulatory role of these exosome-derived miRNAs can be confirmed in SCI.

Citing Articles

Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration.

Yavuz B, Mutlu E, Ahmed Z, Ben-Nissan B, Stamboulis A Int J Mol Sci. 2024; 25(11).

PMID: 38892052 PMC: 11172915. DOI: 10.3390/ijms25115863.

Exosomes Derived from Mesenchymal Stem Cells: Therapeutic Opportunities for Spinal Cord Injury.

Zhang C Bull Exp Biol Med. 2024; 176(6):716-721.

PMID: 38888648 DOI: 10.1007/s10517-024-06095-y.

Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions.

Mirsanei Z, Jamshidi-Adegani F, Vakilian S, Ahangari F, Soufihasanabad S, Al-Riyami K Inflammopharmacology. 2024; 32(2):1317-1332.

PMID: 38512654 DOI: 10.1007/s10787-024-01438-7.

Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury.

Chen S, Chen Y, Li P, Cheng T, Chu Y, Shen Y J Biomed Sci. 2024; 31(1):30.

PMID: 38500170 PMC: 10949767. DOI: 10.1186/s12929-024-01019-4.

Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization.

Liang Z, Yang Z, Xie H, Rao J, Xu X, Lin Y Neural Regen Res. 2024; 19(10):2259-2269.

PMID: 38488560 PMC: 11034578. DOI: 10.4103/1673-5374.391194.

References

Locati M, Curtale G, Mantovani A . Diversity, Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol. 2019; 15:123-147. PMC: 7176483. DOI: 10.1146/annurev-pathmechdis-012418-012718. View

Xu P, Yang X . The Efficacy and Safety of Mesenchymal Stem Cell Transplantation for Spinal Cord Injury Patients: A Meta-Analysis and Systematic Review. Cell Transplant. 2018; 28(1):36-46. PMC: 6322141. DOI: 10.1177/0963689718808471. View

Li Q, Barres B . Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2017; 18(4):225-242. DOI: 10.1038/nri.2017.125. View

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J . The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003; 425(6956):415-9. DOI: 10.1038/nature01957. View

Li K, Ching D, Luk F, Raffai R . Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-κB-driven inflammation and atherosclerosis. Circ Res. 2015; 117(1):e1-e11. PMC: 4475484. DOI: 10.1161/CIRCRESAHA.117.305844. View

Orecchioni M, Ghosheh Y, Pramod A, Ley K . Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Front Immunol. 2019; 10:1084. PMC: 6543837. DOI: 10.3389/fimmu.2019.01084. View

Wang X, Cao K, Sun X, Chen Y, Duan Z, Sun L . Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris. Glia. 2014; 63(4):635-51. PMC: 4331228. DOI: 10.1002/glia.22774. View

Kigerl K, Gensel J, Ankeny D, Alexander J, Donnelly D, Popovich P . Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009; 29(43):13435-44. PMC: 2788152. DOI: 10.1523/JNEUROSCI.3257-09.2009. View

Porta C, Riboldi E, Ippolito A, Sica A . Molecular and epigenetic basis of macrophage polarized activation. Semin Immunol. 2015; 27(4):237-48. DOI: 10.1016/j.smim.2015.10.003. View

10.

Wang R, Xu B . TGF-β1-modified MSC-derived exosomal miR-135b attenuates cartilage injury via promoting M2 synovial macrophage polarization by targeting MAPK6. Cell Tissue Res. 2021; 384(1):113-127. DOI: 10.1007/s00441-020-03319-1. View

11.

El Kasmi K, Stenmark K . Contribution of metabolic reprogramming to macrophage plasticity and function. Semin Immunol. 2015; 27(4):267-75. PMC: 4677817. DOI: 10.1016/j.smim.2015.09.001. View

12.

He X, Dong Z, Cao Y, Wang H, Liu S, Liao L . MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing. Stem Cells Int. 2019; 2019:7132708. PMC: 6754952. DOI: 10.1155/2019/7132708. View

13.

Hutchins A, Diez D, Miranda-Saavedra D . The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief Funct Genomics. 2013; 12(6):489-98. PMC: 3838198. DOI: 10.1093/bfgp/elt028. View

14.

Ke B, Shen X, Ji H, Kamo N, Gao F, Freitas M . HO-1-STAT3 axis in mouse liver ischemia/reperfusion injury: regulation of TLR4 innate responses through PI3K/PTEN signaling. J Hepatol. 2011; 56(2):359-66. PMC: 3444295. DOI: 10.1016/j.jhep.2011.05.023. View

15.

Zhong B, Yang X, Sun Q, Liu L, Lan X, Tian J . Pdcd4 modulates markers of macrophage alternative activation and airway remodeling in antigen-induced pulmonary inflammation. J Leukoc Biol. 2014; 96(6):1065-75. DOI: 10.1189/jlb.3A0313-136RRR. View

16.

Sun G, Li G, Li D, Huang W, Zhang R, Zhang H . hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Mater Sci Eng C Mater Biol Appl. 2018; 89:194-204. DOI: 10.1016/j.msec.2018.04.006. View

17.

Yao M, Cui B, Zhang W, Ma W, Zhao G, Xing L . Exosomal miR-21 secreted by IL-1β-primed-mesenchymal stem cells induces macrophage M2 polarization and ameliorates sepsis. Life Sci. 2020; 264:118658. DOI: 10.1016/j.lfs.2020.118658. View

18.

Fan B, Wei Z, Yao X, Shi G, Cheng X, Zhou X . Microenvironment Imbalance of Spinal Cord Injury. Cell Transplant. 2018; 27(6):853-866. PMC: 6050904. DOI: 10.1177/0963689718755778. View

19.

Swanson L, Katkar G, Tam J, Pranadinata R, Chareddy Y, Coates J . TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin. Proc Natl Acad Sci U S A. 2020; 117(43):26895-26906. PMC: 7604444. DOI: 10.1073/pnas.2011667117. View

20.

Pekny M, Nilsson M . Astrocyte activation and reactive gliosis. Glia. 2005; 50(4):427-434. DOI: 10.1002/glia.20207. View