Systematic Reviews
Copyright ©The Author(s) 2020.
World J Stem Cells. Aug 26, 2020; 12(8): 879-896
Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.879
Table 1 Immune modulation of extracellular vesicles in autoimmune related diseases
DiseaseEVsExpressionMSC-EVs source/ Target moleculesTarget immune cellsPathway(s) involvedRef.
RAMSC derived exosomal miR-150-5pDownBone marrow derived MSC-EVs/MMP 14 and VEGFMacrophagesTGF-β pathwayChen et al[80]
Exosome-encapsulated miR-548a-3pDownTLR4MacrophagesMiR-548a-3p/TLR4/NF-κB axisWang et al[81]
Exosome-encapsulated miR-6089DownTLR4MacrophagesTLR4/NF-κB signaling pathwayXu et al[82]
Exosome-derived lncRNA HotairUpMMP-2 and MMP-13Macrophages-Song et al[83]
Exosomal miR-17UpTGFBR IIT cells-Wang et al[84]
MicroRNA-155UpSHIP-1Macrophages-Kurowska-Stolarska et al[85]
MicroRNA-146Up-Macrophages, T cells, B cells-Nakasa et al[86]
SLEExosomal miR-26aUpPodocyte proteins, actin family members, and intermediate filamentsPodocytes-Ichii et al[99]
Exosomal miRNA-146aUp--Interferon-γ pathwayPerez-Hernandez et al[100]
pSSEV derived LCN2UpTNF-αB cellsTNF-α signalingAqrawi et al[107]
EV derived APMAPUpTNF-αB cellsTNF-α signalingAqrawi et al[107]
EV derived CPNE1UpTNF-αB cellsTNF-α signalingAqrawi et al[107]
IBDMSC-EVsUpBone marrow derived MSC-EVsMacrophagesJAK1/STAT1/STAT6 signaling pathwayCao et al[113]
Breast cancerExosomal PD-L1DownPD-1T cellsPD-L1/ PD-1 pathwayYang et al[120]
Lung cancerEV derived miR-103aUpLung cancer cell derived EVs/PTENMacrophagesPI3K/ AKT and STAT3 axisHsu et al[121]
Pancreatic cancerExosomal miR-301a-3pUpPTENMacrophagesPI3Kγ signaling pathwayWang et al[122]
GVHDMSC-EVsUpT cell derived EVs--Park et al[126]
Table 2 Therapeutic potential of extracellular vesicles
DiseaseEVsExperimental sampleTherapeutic potentialRef.
RAMSC derived exosomal miR-150-5pCollagen induced arthritis mouse modelMiR-150-5p could reduce joint destruction by inhibiting synoviocyte hyperplasia and angiogenesisChen et al[80]
Exosome-encapsulated miR-548a-3pMacrophage-like cellsMiR-548a-3p could inhibit the proliferation and activation of pTHP-1 cells via the TLR4/NF-κB signaling pathwayWang et al[81]
Exosome-encapsulated miR-6089Macrophage-like cellsMiR-6089 could regulate LPS/TLR4-mediated inflammatory responseXu et al[82]
Exosome-derived lncRNA HotairBlood mononuclear cellsHotair may contribute to the dissolution of bone and cartilage matrix through activation of MMP-2 and MMP-13 in osteoclasts and RA synoviocytes. Hotair is more stable and easily detected in body fluidSong et al[83]
Exosomal miR-17Blood mononuclear cellsMiR-17 can suppress regulatory T cell differentiation by inhibiting the expression of TGFBR IIWang et al[84]
MicroRNA-155MiR-155–deficient miceMiR-155–deficient mice are resistant to collagen-induced arthritis, and antigen-specific Th17 cell and autoantibody responses are suppressed markedly to reduce articular inflammationKurowska-Stolarska et al[85]
MicroRNA-146Human RA synovial fibroblastsMiR-146a is expressed in the superficial and sublining layers of synovial tissue, like synovial fibroblasts, macrophages, T cells, and B cellsNakasa et al[86]
SLEExosomal miR-26aFemale B6.MRLc1 and C57BL/6 mice; C57BL/6 (9 mo of age)Podocytes mainly expresse miR-26a in mouse kidneys. Glomerular miR-26a expression in B6.MRLc1 mice correlates negatively with the urinary albumin levels and podocyte specific gene expressionIchii et al[99]
Exosomal miRNA-146aUrine sample of SLE patientsUp-regulated exosomal miRNA-146a is found in the presence of active lupus nephritisPerez-Hernandez et al[100]
pSSEV derived LCN2Saliva and tear samples from pSS patients and healthy controlsEV derived LCN2 is over-expressed in pSS patientsAqrawi et al[107]
EV derived APMAPSaliva and tear samples from pSS patients and healthy controlsEV derived APMAP is over-expressed in pSS patientsAqrawi et al[107]
EV derived CPNE1Saliva and tear samples from pSS patients and healthy controlsEV derived CPNE1 is over-expressed in pSS patientsAqrawi et al[107]
IBDMSC-EVsLPS treated macrophages and an in vivo DSS induced mouse modelEVs promote the up-regulation of pro-inflammatory factors (TNF-α, IL-6, and IL-12) and down-regulation of the anti-inflammatory factor IL-10 in LPS-induced macrophages. EVs promote polarization of M1-like macrophages to an M2-like stateCao et al[113]
Breast cancerExosomal PD-L1MDA-MB-231 (231) human breast cancer cells and 4T1 mouse mammary tumor cells with PD-L1 expression or PD-L1KOExosomal PD-L1 bind to PD-1 on T cells to inhibit T cell activation and killing activitiesYang et al[120]
Lung cancerEV derived miR-103aHuman adenocarcinoma cell lines NCI-H1437, NCI-H1792, and NCI-H2087 and human embryonic kidney HEK293 cellsmiRNA inhibitor could inhibit effectively miR-103a mediated M2-type polarization, improving the cytokine prolife of tumor infiltration macrophagesHsu et al[121]
Pancreatic cancerExosomal miR-301a-3pPancreatic cancer blood samples, Pancreatic cancer cell lines PANC-1, BxPC-3 and monocytic cell line THP-1Pancreatic cells generate miR-301a-3p-rich exosomes in a hypoxic microenvironment, which polarize macrophages to promote malignant behaviors of cancer cellsWang et al[122]
GVHDMSC-EVsKidney samples from acute cellular rejectioniKEA (integrated kidney exosome analysis) shows a high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%)Park et al[126]