Research progress of mesenchymal stem cells derived exosomes in damaged tissue repair and regeneration

doi:10.3969/j.issn.2095-4344.0423

Abstract

Abstract:

BACKGROUND: In the past few years, many studies have shown that mesenchymal stem cells play roles in tissue repair and regeneration, which is to a large extent by their paracrine effect. As one of the important paracrine factors, exosomes have become an issue of concern for researchers.
OBJECTIVE: To explain the components, sources and biological characteristics of exosomes, to summarize the latest research advances of mesenchymal stem cells derived exosomes in tissue repair and regeneration, and to make prospects of its application in the field of oral medicine.
METHODS: A computer-based search of the relevant literature in CNKI and PubMed full-text databases of journals from 1983 to 2017 was performed. The keywords were “exosome, MSC-exosomes, tissue repair and regeneration, oral diseases” in Chinese and English, respectively. Totally 61 eligible articles were included in the result analysis.
RESULTS AND CONCLUSION: Exosome is a vesicle secreted by cells and contains different proteins and RNAs. It plays an important role in the intercellular communication, and has the functions of inhibiting apoptosis, stimulating proliferation and regulating immunity. Mesenchymal stem cells derived exosomes play an important role in repairing bone injury, skin injury, nerve injury and liver injury, but its mechanism is yet unclear. The application of exosomes in the field of oral medicine is rarely reported, which is certainly worthy of further research and exploration.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mesenchymal Stem Cells, Exosomes, Tissue Engineering

CLC Number:

R394.2

Li Chao-ran, Huang Gui-lin, Wang Shuai. Research progress of mesenchymal stem cells derived exosomes in damaged tissue repair and regeneration[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(1): 133-139.

Figures/Tables 1

References

[1] Han C, Sun X, Liu L, et al. Exosomes and Their Therapeutic Potentials of Stem Cells. Stem Cells Int. 2016;2016:7653489.

[2] Lai RC, Yeo RW, Lim SK. Mesenchymal stem cell exosomes. Semin Cell Dev Biol. 2015;40:82-88.

[3] Jeong JO, Han JW, Kim JM, et al. Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ Res. 2011;108(11):1340-1347.

[4] Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97(2):329-339.

[5] Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373-383.

[6] Pan BT, Teng K, Wu C, et al. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 1985;101(3):942-948.

[7] Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262(19):9412-9420.

[8] Breakefield XO, Frederickson RM, Simpson RJ. Gesicles: Microvesicle "cookies" for transient information transfer between cells. Mol Ther. 2011;19(9):1574-1576.

[9] Simpson RJ, Jensen SS, Lim JW. Proteomic profiling of exosomes: current perspectives. Proteomics. 2008;8(19): 4083-4099.

[10] Lou G Chen Z, Zheng M, et al. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med. 2017;49(6):e346.

[11] Fauré J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 2006;31(4): 642-648.

[12] Andre F, Schartz NE, Movassagh M, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002; 360(9329):295-305..

[13] Yáñez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.

[14] Hao ZC, Lu J, Wang SZ, et al. Stem cell-derived exosomes: A promising strategy for fracture healing. Cell Prolif. 2017;50(5). doi: 10.1111/cpr.12359.

[15] Théry C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;Chapter 3:Unit 3.22.

[16] Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med. 2011;6(4):481-492.

[17] Huotari J, Helenius A. Endosome maturation. EMBO J. 2011; 30(17):3481-3500.

[18] Urbanelli L, Magini A, Buratta S, et al. Signaling pathways in exosomes biogenesis, secretion and fate. Genes (Basel). 2013;4(2):152-170.

[19] Yuan A, Farber EL, Rapoport AL, et al. Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One. 2009;4(3): e4722.

[20] Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6): 654-659.

[21] Corrado C, Raimondo S, Chiesi A, et al. Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int J Mol Sci. 2013;14(3):5338-5366.

[22] Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009; 9(8):581-593.

[23] Zhu W, Huang L, Li Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28-37.

[24] McLellan AD.Exosome release by primary B cells. Crit Rev Immunol. 2009;29(3):203-217.

[25] Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016;12(3):655-664.

[26] Chen B, Li Q, Zhao B, et al. Stem Cell-Derived Extracellular Vesicles as a Novel Potential Therapeutic Tool for Tissue Repair. Stem Cells Transl Med. 2017;6(9):1753-1758.

[27] Zhang J, Liu X, Li H, et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res Ther. 2016;7(1):136.

[28] Qi X, Zhang J, Yuan H, et al. Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Repair Critical-Sized Bone Defects through Enhanced Angiogenesis and Osteogenesis in Osteoporotic Rats. Int J Biol Sci. 2016;12(7):836-849.

[29] Furuta T, Miyaki S, Ishitobi H, et al. Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model. Stem Cells Transl Med. 2016;5(12):1620-1630.

[30] Qin Y, Wang L, Gao Z, et al. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci Rep. 2016;6:21961.

[31] Tao SC, Yuan T, Zhang YL, et al. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics. 2017; 7(1):180-195.

[32] Liu X, Yang Y, Li Y, et al. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale. 2017; 9(13):4430-4438.

[33] Zhang B, Wang M, Gong A, et al. HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells. 2015;33(7):2158-2168.

[34] Fang S, Xu C, Zhang Y, et al. Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing. Stem Cells Transl Med. 2016;5(10): 1425-1439.

[35] Hu L, Wang J, Zhou X, et al. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci Rep. 2016;6:32993.

[36] Kang T, Jones TM, Naddell C, et al. Adipose-Derived Stem Cells Induce Angiogenesis via Microvesicle Transport of miRNA-31. Stem Cells Transl Med. 2016;5(4):440-450.

[37] Liang X, Zhang L, Wang S, et al. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci. 2016; 129(11):2182-2189.

[38] Baulch JE, Acharya MM, Allen BD, et al. Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain. Proc Natl Acad Sci U S A. 2016;113(17):4836-4841.

[39] Zhang Y, Chopp M, Liu XS, et al. Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons. Mol Neurobiol. 2017;54(4):2659-2673.

[40] Huang JH, Yin XM, Xu Y, et al. Systemic Administration of Exosomes Released from Mesenchymal Stromal Cells Attenuates Apoptosis, Inflammation, and Promotes Angiogenesis after Spinal Cord Injury in Rats. J Neurotrauma. 2017 Aug 18. [Epub ahead of print]

[41] Chen KH, Chen CH, Wallace CG, et al. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget. 2016;7(46):74537-74556.

[42] Nong K, Wang W, Niu X, et al. Hepatoprotective effect of exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells against hepatic ischemia- reperfusion injury in rats. Cytotherapy. 2016;18(12): 1548-1559.

[43] Yan Y, Jiang W, Tan Y, et al. hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury. Mol Ther. 2017;25(2):465-479.

[44] Tan CY, Lai RC, Wong W, et al. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther. 2014;5(3):76.

[45] Zhang Y, McNeill E, Tian H, et al. Urine derived cells are a potential source for urological tissue reconstruction. J Urol. 2008;180(5):2226-2233.

[46] Yuan H, Guan J, Zhang J, et al. Exosomes secreted by human urine-derived stem cells accelerate skin wound healing by promoting angiogenesis in rat. Cell Biol Int. 2017;41(8):933.

[47] Jiang ZZ, Liu YM, Niu X, et al. Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats. Stem Cell Res Ther. 2016;7:24.

[48] Wang K, Jiang Z, Webster KA, et al. Enhanced Cardioprotection by Human Endometrium Mesenchymal Stem Cells Driven by Exosomal MicroRNA-21. Stem Cells Transl Med. 2017;6(1):209-222.

[49] Rosenberg M, Lutz M, Kühl C, et al. Coculture with hematopoietic stem cells protects cardiomyocytes against apoptosis via paracrine activation of AKT. J Transl Med. 2012;10:115.

[50] Ma J, Zhao Y, Sun L, et al. Exosomes Derived from Akt-Modified Human Umbilical Cord Mesenchymal Stem Cells Improve Cardiac Regeneration and Promote Angiogenesis via Activating Platelet-Derived Growth Factor D. Stem Cells Transl Med. 2017;6(1):51-59.

[51] Yang J, Zhang X, Chen X, et al. Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia. Mol Ther Nucleic Acids. 2017;7:278-287.

[52] Lehmann BD, Paine MS, Brooks AM, et al. Senescence- associated exosome release from human prostate cancer cells. Cancer Res. 2008;68(19):7864-7871.

[53] Beer L, Zimmermann M, Mitterbauer A, et al. Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration. Sci Rep. 2015;5:16662.

[54] Xiao X, Yu S, Li S, et al. Exosomes: decreased sensitivity of lung cancer A549 cells to cisplatin. PLoS One. 2014;9(2):e89534.

[55] Gray WD, French KM, Ghosh-Choudhary S, et al. Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ Res. 2015;116(2):255-263.

[56] Kanemoto S, Nitani R, Murakami T, et al. Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress. Biochem Biophys Res Commun. 2016;480(2):166-172.

[57] Gallego-Perez D, Pal D, Ghatak S, et al. Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue. Nat Nanotechnol. 2017;12(10):974-979.

[58] Hayashi T, Lombaert IM, Hauser BR, et al. Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis. Dev Cell. 2017;40(1):95-103.

[59] Huang CC, Narayanan R, Alapati S, et al. Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration. Biomaterials. 2016;111:103-115.

[60] Michael A, Bajracharya SD, Yuen PS, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis. 2010;16(1):34-38.

[61] Byun JS, Hong SH, Choi JK, et al. Diagnostic profiling of salivary exosomal microRNAs in oral lichen planus patients. Oral Dis. 2015;21(8):987-993.