Exosomes from Mesenchymal Stem Cells Expressing MiR-125b Inhibit Neointimal Hyperplasia Via Myosin IE

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2018 Nov 29

PMID 30484954

Citations 24

Authors

Dongqing Wang

Bin Gao

Jianing Yue

Fei Liu

Yifan Liu

Weiguo Fu

Yi Si

Affiliations

Soon will be listed here.

Abstract

Intercellular communication between mesenchymal stem cells (MSCs) and their target cells in the perivascular environment is modulated by exosomes derived from MSCs. However, the potential role of exosome-mediated microRNA transfer in neointimal hyperplasia remains to be investigated. To evaluate the effects of MSC-derived exosomes (MSC-Exo) on neointimal hyperplasia, their effects upon vascular smooth muscle cell (VSMC) growth in vitro and neointimal hyperplasia in vivo were assessed in a model of balloon-induced vascular injury. Our results showed that MSC-Exo were internalised by VSMCs and inhibited proliferation and migration in vitro. Further analysis revealed that miR-125b was enriched in MSC-Exo, and repressed the expression of myosin 1E (Myo1e) by targeting its 3' untranslated region. Additionally, MSC-Exo and exosomally transferred miR-125b repressed Myo1e expression and suppressed VSMC proliferation and migration and neointimal hyperplasia in vivo. In summary, our findings revealed that MSC-Exo can transfer miR-125b to VSMCs and inhibit VSMC proliferation and migration in vitro and neointimal hyperplasia in vivo by repressing Myo1e, indicating that miR-125b may be a therapeutic target in the treatment of vascular diseases.

Citing Articles

Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy.

Jiang Y, Wei Z, Song Z, Yu M, Huang J, Qian H Drug Deliv Transl Res. 2025; .

PMID: 39873880 DOI: 10.1007/s13346-025-01792-1.

Exosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu's arteritis.

Guo S, Li J, Pang S, Li J, Tian X Arthritis Res Ther. 2025; 27(1):11.

PMID: 39833857 PMC: 11744942. DOI: 10.1186/s13075-025-03475-1.

Hyaluronic acid: An overlooked extracellular vesicle contaminant.

Goncalves J, Ghebosu R, Tan X, Iannotta D, Koifman N, Wolfram J J Extracell Vesicles. 2023; 12(9):e12362.

PMID: 37712345 PMC: 10502654. DOI: 10.1002/jev2.12362.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Vasculopathies and Angiogenesis: Therapeutic Applications and Optimization.

Zhu Y, Liao Z, Mo M, Xiong X Biomolecules. 2023; 13(7).

PMID: 37509145 PMC: 10377109. DOI: 10.3390/biom13071109.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Hype or Hope for Skeletal Muscle Anti-Frailty.

Mahindran E, Wan Kamarul Zaman W, Ahmad Amin Noordin K, Tan Y, Nordin F Int J Mol Sci. 2023; 24(9).

PMID: 37175537 PMC: 10178115. DOI: 10.3390/ijms24097833.

References

Curcio A, Torella D, Indolfi C . Mechanisms of smooth muscle cell proliferation and endothelial regeneration after vascular injury and stenting: approach to therapy. Circ J. 2011; 75(6):1287-96. DOI: 10.1253/circj.cj-11-0366. View

Ju X, Zou H, Liu K, Duan J, Li S, Zhou Z . Meta-analysis of the effect of mesenchymal stem cell transplantation on vascular remodeling after carotid balloon injury in animal models. PLoS One. 2015; 10(3):e0120082. PMC: 4374727. DOI: 10.1371/journal.pone.0120082. View

Lee C, Mitsialis S, Aslam M, Vitali S, Vergadi E, Konstantinou G . Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012; 126(22):2601-11. PMC: 3979353. DOI: 10.1161/CIRCULATIONAHA.112.114173. View

Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H . MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 2007; 100(11):1579-88. DOI: 10.1161/CIRCRESAHA.106.141986. View

Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C . A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 2009; 104(4):476-87. PMC: 2728290. DOI: 10.1161/CIRCRESAHA.108.185363. View

de Veirman K, Wang J, Xu S, Leleu X, Himpe E, Maes K . Induction of miR-146a by multiple myeloma cells in mesenchymal stromal cells stimulates their pro-tumoral activity. Cancer Lett. 2016; 377(1):17-24. DOI: 10.1016/j.canlet.2016.04.024. View

Zhao L, Luo H, Li X, Li T, He J, Qi Q . Exosomes Derived from Human Pulmonary Artery Endothelial Cells Shift the Balance between Proliferation and Apoptosis of Smooth Muscle Cells. Cardiology. 2017; 137(1):43-53. DOI: 10.1159/000453544. View

Feeser E, Ignacio C, Krendel M, Ostap E . Myo1e binds anionic phospholipids with high affinity. Biochemistry. 2010; 49(43):9353-60. PMC: 2976041. DOI: 10.1021/bi1012657. View

Cordes K, Sheehy N, White M, Berry E, Morton S, Muth A . miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009; 460(7256):705-10. PMC: 2769203. DOI: 10.1038/nature08195. View

10.

Tallquist M, Kazlauskas A . PDGF signaling in cells and mice. Cytokine Growth Factor Rev. 2004; 15(4):205-13. DOI: 10.1016/j.cytogfr.2004.03.003. View

11.

Mwipatayi B, Hockings A, Hofmann M, Garbowski M, Sieunarine K . Balloon angioplasty compared with stenting for treatment of femoropopliteal occlusive disease: a meta-analysis. J Vasc Surg. 2007; 47(2):461-9. DOI: 10.1016/j.jvs.2007.07.059. View

12.

Gu J, Zhang H, Ji B, Jiang H, Zhao T, Jiang R . Vesicle miR-195 derived from Endothelial Cells Inhibits Expression of Serotonin Transporter in Vessel Smooth Muscle Cells. Sci Rep. 2017; 7:43546. PMC: 5341127. DOI: 10.1038/srep43546. View

13.

London G, Guerin A, Marchais S, Metivier F, Pannier B, Adda H . Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003; 18(9):1731-40. DOI: 10.1093/ndt/gfg414. View

14.

Dai Y, Xu M, Wang Y, Pasha Z, Li T, Ashraf M . HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol. 2007; 42(6):1036-44. PMC: 1995444. DOI: 10.1016/j.yjmcc.2007.04.001. View

15.

Su S, Xie Y, Fu Z, Wang Y, Wang J, Xiang M . Emerging role of exosome-mediated intercellular communication in vascular remodeling. Oncotarget. 2017; 8(15):25700-25712. PMC: 5421963. DOI: 10.18632/oncotarget.14878. View

16.

Liu R, Shen H, Ma J, Sun L, Wei M . Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Regulate the Phenotype of Smooth Muscle Cells to Limit Intimal Hyperplasia. Cardiovasc Drugs Ther. 2015; 30(2):111-8. DOI: 10.1007/s10557-015-6630-5. View

17.

Lai R, Arslan F, Lee M, Sze N, Choo A, Chen T . Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010; 4(3):214-22. DOI: 10.1016/j.scr.2009.12.003. View

18.

Wenzel J, Ouderkirk J, Krendel M, Lang R . Class I myosin Myo1e regulates TLR4-triggered macrophage spreading, chemokine release, and antigen presentation via MHC class II. Eur J Immunol. 2014; 45(1):225-37. PMC: 4293287. DOI: 10.1002/eji.201444698. View

19.

Wu X, Huang L, Zhou Q, Song Y, Li A, Jin J . Mesenchymal stem cells participating in ex vivo endothelium repair and its effect on vascular smooth muscle cells growth. Int J Cardiol. 2005; 105(3):274-82. DOI: 10.1016/j.ijcard.2004.12.090. View

20.

Stoorvogel W . Functional transfer of microRNA by exosomes. Blood. 2012; 119(3):646-8. DOI: 10.1182/blood-2011-11-389478. View