Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Potential Druggability of Mesenchymal Stem/Stromal Cell-derived Exosomes

Author(s): Fan Zhang, Leisheng Zhang and Hao Yu*

Volume 19, Issue 9, 2024

Published on: 22 March, 2024

Page: [1195 - 1209] Pages: 15

DOI: 10.2174/011574888X311270240319084835

Price: $65

conference banner
Abstract

Exosomes secreted by mesenchymal stem/stromal cells (MSC-Exos) are advantageous candidate sources for novel acellular therapy. Despite the current standards of good manufacturing practice (GMP), the deficiency of suitable quality-control methods and the difficulties in large-scale preparation largely restrict the development of therapeutic products and their clinical applications worldwide. Herein, we mainly focus on three dominating issues commonly encountered in exosomal GMP, including issues upstream of the cell culture process, downstream of the purification process, exosomes quality control, and the drug properties of exosomes and their druggability from a corporate perspective. Collectively, in this review article, we put forward the issues of preparing clinical exosome drugs for the treatment of diverse diseases and provide new references for the clinical application of GMP-grade MSC-Exos.

Keywords: Exosomes, druggability, quality control, autocrine, sucrose, clinical application.

« Previous Next »
Graphical Abstract

[1]
de Girolamo L, Lucarelli E, Alessandri G, et al. Mesenchymal stem/stromal cells: A new “cells as drugs” paradigm. Efficacy and critical aspects in cell therapy. Curr Pharm Des 2013; 19(13): 2459-73.
[http://dx.doi.org/10.2174/1381612811319130015] [PMID: 23278600]
[2]
Ciccocioppo R, Cangemi GC, Kruzliak P, et al. Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn’s disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact. Stem Cell Res Ther 2015; 6(1): 137.
[http://dx.doi.org/10.1186/s13287-015-0122-1] [PMID: 26206376]
[3]
Gnecchi M, He H, Liang OD, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005; 11(4): 367-8.
[http://dx.doi.org/10.1038/nm0405-367] [PMID: 15812508]
[4]
Noonin C, Thongboonkerd V. Exosome-inflammasome crosstalk and their roles in inflammatory responses. Theranostics 2021; 11(9): 4436-51.
[http://dx.doi.org/10.7150/thno.54004] [PMID: 33754070]
[5]
Ludwig AK, Giebel B. Exosomes: Small vesicles participating in intercellular communication. Int J Biochem Cell Biol 2012; 44(1): 11-5.
[http://dx.doi.org/10.1016/j.biocel.2011.10.005] [PMID: 22024155]
[6]
Reiner AT, Witwer KW, van Balkom BWM, et al. Concise review: Developing best-practice models for the therapeutic use of extracellular vesicles. Stem Cells Transl Med 2017; 6(8): 1730-9.
[http://dx.doi.org/10.1002/sctm.17-0055] [PMID: 28714557]
[7]
Xian P, Hei Y, Wang R, et al. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice. Theranostics 2019; 9(20): 5956-75.
[http://dx.doi.org/10.7150/thno.33872] [PMID: 31534531]
[8]
Ailawadi S, Wang X, Gu H, Fan GC. Pathologic function and therapeutic potential of exosomes in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis 2015; 1852(1): 1-11.
[http://dx.doi.org/10.1016/j.bbadis.2014.10.008] [PMID: 25463630]
[9]
Kulshreshtha A, Ahmad T, Agrawal A, Ghosh B. Proinflammatory role of epithelial cell–derived exosomes in allergic airway inflammation. J Allergy Clin Immunol 2013; 131(4): 1194-1203.e14, 1203.e1-1203.e14.
[http://dx.doi.org/10.1016/j.jaci.2012.12.1565] [PMID: 23414598]
[10]
Zhang S, Teo KYW, Chuah SJ, Lai RC, Lim SK, Toh WS. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials 2019; 200: 35-47.
[http://dx.doi.org/10.1016/j.biomaterials.2019.02.006] [PMID: 30771585]
[11]
Lou G, Chen Z, Zheng M, Liu Y. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med 2017; 49(6): e346.
[http://dx.doi.org/10.1038/emm.2017.63] [PMID: 28620221]
[12]
Harrell CR, Simovic Markovic B, Fellabaum C, et al. Therapeutic potential of mesenchymal stem cell-derived exosomes in the treatment of eye diseases. Adv Exp Med Biol 2018; 1089: 47-57.
[http://dx.doi.org/10.1007/5584_2018_219] [PMID: 29774506]
[13]
Sengupta V, Sengupta S, Lazo A, Woods P, Nolan A, Bremer N. Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19. Stem Cells Dev 2020; 29(12): 747-54.
[http://dx.doi.org/10.1089/scd.2020.0080] [PMID: 32380908]
[14]
Pu X, Zhang L, Zhang P, et al. Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency. Front Endocrinol 2023; 14: 1205901.
[http://dx.doi.org/10.3389/fendo.2023.1205901] [PMID: 37564988]
[15]
Ha DH, Kim H, Lee J, et al. Mesenchymal stem/stromal cell-derived exosomes for immunomodulatory therapeutics and skin regeneration. Cells 2020; 9(5): 1157.
[http://dx.doi.org/10.3390/cells9051157] [PMID: 32392899]
[16]
Basisty Nathan. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biology 2020; 18(1): e3000599.
[http://dx.doi.org/10.1371/journal.pbio.3000599]
[17]
Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in clinical trials – An ISEV position paper. J Extracell Vesicles 2015; 4(1): 30087.
[http://dx.doi.org/10.3402/jev.v4.30087] [PMID: 26725829]
[18]
Yang XX, Sun C, Wang L, Guo XL. New insight into isolation, identification techniques and medical applications of exosomes. J Control Release 2019; 308: 119-29.
[http://dx.doi.org/10.1016/j.jconrel.2019.07.021] [PMID: 31325471]
[19]
Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods 2015; 87: 3-10.
[http://dx.doi.org/10.1016/j.ymeth.2015.02.019] [PMID: 25766927]
[20]
Colao IL, Corteling R, Bracewell D, Wall I. Manufacturing exosomes: A promising therapeutic platform. Trends Mol Med 2018; 24(3): 242-56.
[http://dx.doi.org/10.1016/j.molmed.2018.01.006] [PMID: 29449149]
[21]
Patel DB, Santoro M, Born LJ, Fisher JP, Jay SM. Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment. Biotechnol Adv 2018; 36(8): 2051-9.
[http://dx.doi.org/10.1016/j.biotechadv.2018.09.001] [PMID: 30218694]
[22]
Aslam M, Baveja R, Liang OD, et al. Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med 2009; 180(11): 1122-30.
[http://dx.doi.org/10.1164/rccm.200902-0242OC] [PMID: 19713447]
[23]
Zhang Y, Chopp M, Meng Y, et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J Neurosurg 2015; 122(4): 856-67.
[http://dx.doi.org/10.3171/2014.11.JNS14770] [PMID: 25594326]
[24]
Lai RC, Arslan F, Lee MM, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 2010; 4(3): 214-22.
[http://dx.doi.org/10.1016/j.scr.2009.12.003] [PMID: 20138817]
[25]
Zhang G, Wang D, Miao S, Zou X, Liu G, Zhu Y. Extracellular vesicles derived from mesenchymal stromal cells may possess increased therapeutic potential for acute kidney injury compared with conditioned medium in rodent models: A meta-analysis. Exp Ther Med 2016; 11(4): 1519-25.
[http://dx.doi.org/10.3892/etm.2016.3076] [PMID: 27073476]
[26]
Willis GR, Kourembanas S, Mitsialis SA. Toward exosome-based therapeutics: Isolation, heterogeneity, and fit-for-purpose potency. Front Cardiovasc Med 2017; 4: 63.
[http://dx.doi.org/10.3389/fcvm.2017.00063] [PMID: 29062835]
[27]
Willis GR, Fernandez-Gonzalez A, Anastas J, et al. Mesenchymal stromal cell exosomes ameliorate experimental bronchopulmonary dysplasia and restore lung function through macrophage immunomodulation. Am J Respir Crit Care Med 2018; 197(1): 104-16.
[http://dx.doi.org/10.1164/rccm.201705-0925OC] [PMID: 28853608]
[28]
Lee C, Mitsialis SA, Aslam M, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation 2012; 126(22): 2601-11.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.114173] [PMID: 23114789]
[29]
Aliotta JM, Pereira M, Wen S, et al. Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice. Cardiovasc Res 2016; 110(3): 319-30.
[http://dx.doi.org/10.1093/cvr/cvw054] [PMID: 26980205]
[30]
Phinney DG, Di Giuseppe M, Njah J, et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun 2015; 6(1): 8472.
[http://dx.doi.org/10.1038/ncomms9472] [PMID: 26442449]
[31]
Yu B, Kim HW, Gong M, et al. Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. Int J Cardiol 2015; 182: 349-60.
[http://dx.doi.org/10.1016/j.ijcard.2014.12.043] [PMID: 25590961]
[32]
Teng X, Chen L, Chen W, Yang J, Yang Z, Shen Z. Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cell Physiol Biochem 2015; 37(6): 2415-24.
[http://dx.doi.org/10.1159/000438594] [PMID: 26646808]
[33]
Kim SU, Lee HJ, Kim YB. Neural stem cell-based treatment for neurodegenerative diseases. Neuropathology 2013; 33(5): 491-504.
[http://dx.doi.org/10.1111/neup.12020] [PMID: 23384285]
[34]
Yu B, Shao H, Su C, et al. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep 2016; 6(1): 34562.
[http://dx.doi.org/10.1038/srep34562] [PMID: 27686625]
[35]
Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through mirna-dependent mechanisms: Exosome-mediated retinal repair. Stem Cells Transl Med 2017; 6(4): 1273-85.
[http://dx.doi.org/10.1002/sctm.16-0428] [PMID: 28198592]
[36]
Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab 2013; 33(11): 1711-5.
[http://dx.doi.org/10.1038/jcbfm.2013.152] [PMID: 23963371]
[37]
Theocharidis U, Long K, ffrench-Constant C, Faissner A. Regulation of the neural stem cell compartment by extracellular matrix constituents. Prog Brain Res 2014; 214: 3-28.
[http://dx.doi.org/10.1016/B978-0-444-63486-3.00001-3] [PMID: 25410351]
[38]
Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013; 22(6): 845-54.
[http://dx.doi.org/10.1089/scd.2012.0395] [PMID: 23002959]
[39]
Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med 2015; 13(1): 49.
[http://dx.doi.org/10.1186/s12967-015-0417-0] [PMID: 25638205]
[40]
Aalberts M, van Dissel-Emiliani FMF, van Adrichem NPH, et al. Identification of distinct populations of prostasomes that differentially express prostate stem cell antigen, annexin A1, and GLIPR2 in humans. Biol Reprod 2012; 86(3): 82.
[http://dx.doi.org/10.1095/biolreprod.111.095760] [PMID: 22133690]
[41]
Huang L, Ma W, Ma Y, Feng D, Chen H, Cai B. Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases? Int J Biol Sci 2015; 11(2): 238-45.
[http://dx.doi.org/10.7150/ijbs.10725] [PMID: 25632267]
[42]
Lai RC, Tan SS, Teh BJ, et al. Proteolytic potential of the msc exosome proteome: Implications for an exosome-mediated delivery of therapeutic proteasome. Int J Proteomics 2012; 2012: 1-14.
[http://dx.doi.org/10.1155/2012/971907] [PMID: 22852084]
[43]
Deregibus MC, Cantaluppi V, Calogero R, et al. Endothelial progenitor cell–derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007; 110(7): 2440-8.
[http://dx.doi.org/10.1182/blood-2007-03-078709] [PMID: 17536014]
[44]
Xin H, Li Y, Chopp M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front Cell Neurosci 2014; 8: 377.
[http://dx.doi.org/10.3389/fncel.2014.00377] [PMID: 25426026]
[45]
Lusardi TA, Murphy SJ, Phillips JI, et al. MicroRNA responses to focal cerebral ischemia in male and female mouse brain. Front Mol Neurosci 2014; 7: 11.
[http://dx.doi.org/10.3389/fnmol.2014.00011] [PMID: 24574964]
[46]
Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep 2013; 3(1): 1197.
[http://dx.doi.org/10.1038/srep01197] [PMID: 23378928]
[47]
Zhang B, Yin Y, Lai RC, Tan SS, Choo ABH, Lim SK. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev 2014; 23(11): 1233-44.
[http://dx.doi.org/10.1089/scd.2013.0479] [PMID: 24367916]
[48]
Peng S, Sun C, Lai C, Zhang L. Exosomes derived from mesenchymal stem cells rescue cartilage injury in osteoarthritis through Ferroptosis by GOT1/CCR2 expression. Int Immunopharmacol 2023; 122: 110566.
[http://dx.doi.org/10.1016/j.intimp.2023.110566] [PMID: 37418985]
[49]
Wang X, Gu H, Qin D, et al. Exosomal miR-223 contributes to mesenchymal stem cell-elicited cardioprotection in polymicrobial sepsis. Sci Rep 2015; 5(1): 13721.
[http://dx.doi.org/10.1038/srep13721] [PMID: 26348153]
[50]
Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 2013; 31(12): 2737-46.
[http://dx.doi.org/10.1002/stem.1409] [PMID: 23630198]
[51]
Hsu S, Wang B, Kota J, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Invest 2012; 122(8): 2871-83.
[http://dx.doi.org/10.1172/JCI63539] [PMID: 22820288]
[52]
Huang F, Zhu X, Hu XQ, et al. Mesenchymal stem cells modified with miR-126 release angiogenic factors and activate Notch ligand Delta-like-4, enhancing ischemic angiogenesis and cell survival. Int J Mol Med 2013; 31(2): 484-92.
[http://dx.doi.org/10.3892/ijmm.2012.1200] [PMID: 23229021]
[53]
Yuan O, Lin C, Wagner J, et al. Exosomes derived from human primed mesenchymal stem cells induce mitosis and potentiate growth factor secretion. Stem Cells Dev 2019; 28(6): 398-409.
[http://dx.doi.org/10.1089/scd.2018.0200] [PMID: 30638129]
[54]
Cui Y, Fu S, Sun D, Xing J, Hou T, Wu X. EPC -derived exosomes promote osteoclastogenesis through Lnc RNA-MALAT 1. J Cell Mol Med 2019; 23(6): 3843-54.
[http://dx.doi.org/10.1111/jcmm.14228] [PMID: 31025509]
[55]
Claudia Lo, Sicco Daniele, Reverberi Carolina. Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects: Endorsement of macrophage polarization. Stem cells Transl Med 2017; 6(3): 1018-28.
[56]
Zhu J, Liu B, Wang Z, et al. Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p/PTEN-mediated VSMC migration and proliferation. Theranostics 2019; 9(23): 6901-19.
[http://dx.doi.org/10.7150/thno.37357] [PMID: 31660076]
[57]
Gudiseva HV, Vrathasha V, He J, Bungatavula D, O’Brien JM, Chavali VRM. Single cell sequencing of induced pluripotent stem cell derived retinal ganglion cells (ipsc-rgc) reveals distinct molecular signatures and rgc subtypes. Genes 2021; 12(12): 2015.
[http://dx.doi.org/10.3390/genes12122015] [PMID: 34946963]
[58]
Cai X, Qu L, Yang J, et al. Exosome–transmitted microRNA-133b inhibited bladder cancer proliferation by upregulating dual-specificity protein phosphatase 1. Cancer Med 2020; 9(16): 6009-19.
[http://dx.doi.org/10.1002/cam4.3263] [PMID: 32627968]
[59]
Smolarz M, Widlak P. Serum exosomes and their mirna load—a potential biomarker of lung cancer. Cancers 2021; 13(6): 1373.
[http://dx.doi.org/10.3390/cancers13061373] [PMID: 33803617]
[60]
Han C, Zhou J, Liu B, et al. Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb. Mater Sci Eng C 2019; 99: 322-32.
[http://dx.doi.org/10.1016/j.msec.2019.01.122] [PMID: 30889706]
[61]
Wang B, Zhang A, Wang H, et al. MiR-26a limits muscle wasting and cardiac fibrosis through exosome-mediated microrna transfer in chronic kidney disease. Theranostics 2019; 9(7): 1864-77.
[http://dx.doi.org/10.7150/thno.29579] [PMID: 31037144]
[62]
Matsuzaki K, Fujita K, Tomiyama E, et al. MiR-30b-3p and miR-126-3p of urinary extracellular vesicles could be new biomarkers for prostate cancer. Transl Androl Urol 2021; 10(4): 1918-27.
[http://dx.doi.org/10.21037/tau-20-421] [PMID: 33968679]
[63]
Wang J, Xia J, Huang R, et al. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res Ther 2020; 11(1): 424.
[http://dx.doi.org/10.1186/s13287-020-01937-8] [PMID: 32993783]
[64]
Iglesias DM, El-Kares R, Taranta A, et al. Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro. PLoS One 2012; 7(8): e42840.
[http://dx.doi.org/10.1371/journal.pone.0042840] [PMID: 22912749]
[65]
Eiró N, Sendon-Lago J, Seoane S, et al. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells. Oncotarget 2014; 5(21): 10692-708.
[http://dx.doi.org/10.18632/oncotarget.2530] [PMID: 25296979]
[66]
Bermudez MA, Sendon-Lago J, Seoane S, et al. Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis. Exp Eye Res 2016; 149: 84-92.
[http://dx.doi.org/10.1016/j.exer.2016.06.022] [PMID: 27381329]
[67]
Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng Part A 2012; 18(13-14): 1479-89.
[http://dx.doi.org/10.1089/ten.tea.2011.0325] [PMID: 22443121]
[68]
Ye C, Li H, Bao M, Zhuo R, Jiang G, Wang W. Alveolar macrophage - derived exosomes modulate severity and outcome of acute lung injury. Aging 2020; 12(7): 6120-8.
[http://dx.doi.org/10.18632/aging.103010] [PMID: 32259794]
[69]
An T, Chen Y, Tu Y, Lin P. Mesenchymal stromal cell-derived extracellular vesicles in the treatment of diabetic foot ulcers: Application and challenges. Stem Cell Rev Rep 2021; 17(2): 369-78.
[http://dx.doi.org/10.1007/s12015-020-10014-9] [PMID: 32772239]
[70]
Maksimova NV, Michenko AV, Krasilnikova OA, et al. Mesenchymal stromal cell therapy alone does not lead to complete restoration of skin parameters in diabetic foot patients within a 3-year follow-up period. Bioimpacts 2022; 12(1): 51-5.
[PMID: 35087716]
[71]
Mautner K, Gottschalk M, Boden SD, et al. Cell-based versus corticosteroid injections for knee pain in osteoarthritis: A randomized phase 3 trial. Nat Med 2023; 29(12): 3120-6.
[http://dx.doi.org/10.1038/s41591-023-02632-w] [PMID: 37919438]
[72]
Witwer KW, Buzás EI, Bemis LT, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2013; 2(1): 20360.
[http://dx.doi.org/10.3402/jev.v2i0.20360] [PMID: 24009894]
[73]
Yuana Y, Böing AN, Grootemaat AE, et al. Handling and storage of human body fluids for analysis of extracellular vesicles. J Extracell Vesicles 2015; 4(1): 29260.
[http://dx.doi.org/10.3402/jev.v4.29260] [PMID: 26563735]
[74]
Van Deun J, Mestdagh P, Agostinis P, et al. EV-TRACK: Transparent reporting and centralizing knowledge in extracellular vesicle research. Nat Methods 2017; 14(3): 228-32.
[http://dx.doi.org/10.1038/nmeth.4185] [PMID: 28245209]
[75]
Shelke GV, Lässer C, Gho YS, Lötvall J. Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum. J Extracell Vesicles 2014; 3(1): 24783.
[http://dx.doi.org/10.3402/jev.v3.24783] [PMID: 25317276]
[76]
Pachler K, Lener T, Streif D, et al. A good manufacturing practice–grade standard protocol for exclusively human mesenchymal stromal cell–derived extracellular vesicles. Cytotherapy 2017; 19(4): 458-72.
[http://dx.doi.org/10.1016/j.jcyt.2017.01.001] [PMID: 28188071]
[77]
Lamparski HG, Metha-Damani A, Yao JY, et al. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 2002; 270(2): 211-26.
[http://dx.doi.org/10.1016/S0022-1759(02)00330-7] [PMID: 12379326]
[78]
Andriolo G, Provasi E, Lo Cicero V, et al. Exosomes from human cardiac progenitor cells for therapeutic applications: Development of a gmp-grade manufacturing method. Front Physiol 2018; 9: 1169.
[http://dx.doi.org/10.3389/fphys.2018.01169] [PMID: 30197601]
[79]
Mendt M, Kamerkar S, Sugimoto H, et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 2018; 3(8): e99263.
[http://dx.doi.org/10.1172/jci.insight.99263] [PMID: 29669940]
[80]
Becquart P, Cambon-Binder A, Monfoulet LE, et al. Ischemia is the prime but not the only cause of human multipotent stromal cell death in tissue-engineered constructs in vivo. Tissue Eng Part A 2012; 18(19-20): 2084-94.
[http://dx.doi.org/10.1089/ten.tea.2011.0690] [PMID: 22578283]
[81]
Yu J, Yin S, Zhang W, et al. Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver regeneration in a rat massive hepatectomy model. Stem Cell Res Ther 2013; 4(4): 83.
[http://dx.doi.org/10.1186/scrt234] [PMID: 23856418]
[82]
Brennan MÁ, Layrolle P, Mooney DJ. Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration. Adv Funct Mater 2020; 30(37): 1909125.
[http://dx.doi.org/10.1002/adfm.201909125] [PMID: 32952493]
[83]
Liu L, Gao J, Yuan Y, Chang Q, Liao Y, Lu F. Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol Int 2013; 37(6): 551-60.
[http://dx.doi.org/10.1002/cbin.10097] [PMID: 23505143]
[84]
Chang CP, Chio CC, Cheong CU, Chao CM, Cheng BC, Lin MT. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci 2013; 124(3): 165-76.
[http://dx.doi.org/10.1042/CS20120226] [PMID: 22876972]
[85]
Lee SC, Jeong HJ, Lee SK, Kim SJ. Hypoxic conditioned medium from human adipose-derived stem cells promotes mouse liver regeneration through jak/stat3 signaling. Stem Cells Transl Med 2016; 5(6): 816-25.
[http://dx.doi.org/10.5966/sctm.2015-0191] [PMID: 27102647]
[86]
Anderson JD, Johansson HJ, Graham CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappab signaling. Stem Cells 2016; 34(3): 601-13.
[http://dx.doi.org/10.1002/stem.2298] [PMID: 26782178]
[87]
Zhu J, Lu K, Zhang N, et al. Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA-210 in an nSMase2-dependent way. Artif Cells Nanomed Biotechnol 2018; 46(8): 1659-70.
[PMID: 29141446]
[88]
Tang H, He Y, Li L, et al. Exosomal MMP2 derived from mature osteoblasts promotes angiogenesis of endothelial cells via VEGF/Erk1/2 signaling pathway. Exp Cell Res 2019; 383(2): 111541.
[http://dx.doi.org/10.1016/j.yexcr.2019.111541] [PMID: 31369752]
[89]
Bartosh TJ, Ylöstalo JH, Mohammadipoor A, et al. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci USA 2010; 107(31): 13724-9.
[http://dx.doi.org/10.1073/pnas.1008117107] [PMID: 20643923]
[90]
Waters R, Alam P, Pacelli S, Chakravarti AR, Ahmed RPH, Paul A. Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue. Acta Biomater 2018; 69: 95-106.
[http://dx.doi.org/10.1016/j.actbio.2017.12.025] [PMID: 29281806]
[91]
Long R, Wang S. Exosomes from preconditioned mesenchymal stem cells: Tissue repair and regeneration. Regen Ther 2024; 25: 355-66.
[http://dx.doi.org/10.1016/j.reth.2024.01.009] [PMID: 38374989]
[92]
Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin 2017; 38(6): 754-63.
[http://dx.doi.org/10.1038/aps.2017.12] [PMID: 28392567]
[93]
Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018; 7(1): 1535750.
[http://dx.doi.org/10.1080/20013078.2018.1535750] [PMID: 30637094]
[94]
Mora E, Álvarez-Cubela S, Oltra E. Biobanking of exosomes in the era of precision medicine: Are we there yet? Int J Mol Sci 2015; 17(1): 13.
[http://dx.doi.org/10.3390/ijms17010013] [PMID: 26712742]
[95]
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics 2017; 7(3): 789-804.
[http://dx.doi.org/10.7150/thno.18133] [PMID: 28255367]
[96]
Miranda KC, Bond DT, Levin JZ, et al. Massively parallel sequencing of human urinary exosome/microvesicle RNA reveals a predominance of non-coding RNA. PLoS One 2014; 9(5): e96094.
[http://dx.doi.org/10.1371/journal.pone.0096094] [PMID: 24816817]
[97]
Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 2019; 21(1): 9-17.
[http://dx.doi.org/10.1038/s41556-018-0250-9] [PMID: 30602770]
[98]
Zarovni N, Corrado A, Guazzi P, et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods 2015; 87: 46-58.
[http://dx.doi.org/10.1016/j.ymeth.2015.05.028] [PMID: 26044649]
[99]
Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol 2006; 30(1): 22.
[http://dx.doi.org/10.1002/0471143030.cb0322s30] [PMID: 18228490]
[100]
Albertsson P, Frick G. Partition of virus particles in a liquid two-phase system. Biochim Biophys Acta 1960; 37(2): 230-7.
[http://dx.doi.org/10.1016/0006-3002(60)90228-6] [PMID: 13792408]
[101]
Zeringer E, Barta T, Li M, Vlassov AV. Strategies for isolation of exosomes. Cold Spring Harb Protoc 2015; 2015(4): pdb.top074476.
[http://dx.doi.org/10.1101/pdb.top074476] [PMID: 25834266]
[102]
Chang M, Chang YJ, Chao PY, Yu Q. Exosome purification based on PEG-coated Fe3O4 nanoparticles. PLoS One 2018; 13(6): e0199438.
[http://dx.doi.org/10.1371/journal.pone.0199438] [PMID: 29933408]
[103]
Jackson KK, Powell RR, Bruce TF, Marcus RK. Rapid isolation of extracellular vesicles from diverse biofluid matrices via capillary-channeled polymer fiber solid-phase extraction micropipette tips. Analyst 2021; 146(13): 4314-25.
[http://dx.doi.org/10.1039/D1AN00373A] [PMID: 34105528]
[104]
Burgess RR. A brief practical review of size exclusion chromatography: Rules of thumb, limitations, and troubleshooting. Protein Expr Purif 2018; 150: 81-5.
[http://dx.doi.org/10.1016/j.pep.2018.05.007] [PMID: 29777748]
[105]
Paul-Dauphin S, Karaca F, Morgan TJ, Millan-Agorio M, Herod AA, Kandiyoti R. Probing size exclusion mechanisms of complex hydrocarbon mixtures: The effect of altering eluent compositions. Energy Fuels 2007; 21(6): 3484-9.
[http://dx.doi.org/10.1021/ef700410e]
[106]
van Eijndhoven MAJ, Zijlstra JM, Groenewegen NJ, et al. Plasma vesicle miRNAs for therapy response monitoring in Hodgkin lymphoma patients. JCI Insight 2016; 1(19): e89631.
[http://dx.doi.org/10.1172/jci.insight.89631] [PMID: 27882350]
[107]
van der Pol E, Böing AN, Gool EL, Nieuwland R. Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. J Thromb Haemost 2016; 14(1): 48-56.
[http://dx.doi.org/10.1111/jth.13190] [PMID: 26564379]
[108]
Kreimer S, Ivanov AR. Rapid isolation of extracellular vesicles from blood plasma with size-exclusion chromatography followed by mass spectrometry-based proteomic profiling. Methods Mol Biol 2017; 1660: 295-302.
[http://dx.doi.org/10.1007/978-1-4939-7253-1_24] [PMID: 28828666]
[109]
Sun Y, Huo C, Qiao Z, et al. Comparative proteomic analysis of exosomes and microvesicles in human saliva for lung cancer. J Proteome Res 2018; 17(3): 1101-7.
[http://dx.doi.org/10.1021/acs.jproteome.7b00770] [PMID: 29397740]
[110]
Salih M, Demmers JA, Bezstarosti K, et al. Proteomics of urinary vesicles links plakins and complement to polycystic kidney disease. J Am Soc Nephrol 2016; 27(10): 3079-92.
[http://dx.doi.org/10.1681/ASN.2015090994] [PMID: 26940098]
[111]
Karimi N, Cvjetkovic A, Jang SC, et al. Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins. Cell Mol Life Sci 2018; 75(15): 2873-86.
[http://dx.doi.org/10.1007/s00018-018-2773-4] [PMID: 29441425]
[112]
Whitesides GM. The origins and the future of microfluidics. Nature 2006; 442(7101): 368-73.
[http://dx.doi.org/10.1038/nature05058] [PMID: 16871203]
[113]
Navabi H, Croston D, Hobot J, et al. Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial. Blood Cells Mol Dis 2005; 35(2): 149-52.
[http://dx.doi.org/10.1016/j.bcmd.2005.06.008] [PMID: 16061407]
[114]
Bak A, Friis KP, Wu Y, Ho RJY. Translating cell and gene biopharmaceutical products for health and market impact. product scaling from clinical to marketplace: Lessons learned and future outlook. J Pharm Sci 2019; 108(10): 3169-75.
[http://dx.doi.org/10.1016/j.xphs.2019.05.027] [PMID: 31150697]
[115]
Sanchez LM, Alvarez VA. Advances in magnetic noble metal/iron-based oxide hybrid nanoparticles as biomedical devices. Bioengineering 2019; 6(3): 75.
[http://dx.doi.org/10.3390/bioengineering6030075] [PMID: 31466238]
[116]
van der Pol E, Coumans FAW, Grootemaat AE, et al. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost 2014; 12(7): 1182-92.
[http://dx.doi.org/10.1111/jth.12602] [PMID: 24818656]
[117]
Tian X, Nejadnik MR, Baunsgaard D, Henriksen A, Rischel C, Jiskoot W. A comprehensive evaluation of nanoparticle tracking analysis (nanosight) for characterization of proteinaceous submicron particles. J Pharm Sci 2016; 105(11): 3366-75.
[http://dx.doi.org/10.1016/j.xphs.2016.08.009] [PMID: 27663383]
[118]
Carnell-Morris P, Tannetta D, Siupa A, Hole P, Dragovic R. Analysis of extracellular vesicles using fluorescence nanoparticle tracking analysis. Methods Mol Biol 2017; 1660: 153-73.
[http://dx.doi.org/10.1007/978-1-4939-7253-1_13] [PMID: 28828655]
[119]
Ma L, Zhu S, Tian Y, et al. Label-free analysis of single viruses with a resolution comparable to that of electron microscopy and the throughput of flow cytometry. Angew Chem Int Ed 2016; 55(35): 10239-43.
[http://dx.doi.org/10.1002/anie.201603007] [PMID: 27457402]
[120]
Nizamudeen Z, Markus R, Lodge R, et al. Rapid and accurate analysis of stem cell-derived extracellular vesicles with super resolution microscopy and live imaging. Biochim Biophys Acta Mol Cell Res 2018; 1865(12): 1891-900.
[http://dx.doi.org/10.1016/j.bbamcr.2018.09.008] [PMID: 30290236]
[121]
Kabe Y, Suematsu M, Sakamoto S, et al. Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera. Clin Chem 2018; 64(10): 1463-73.
[http://dx.doi.org/10.1373/clinchem.2018.291963] [PMID: 30021922]
[122]
Görgens A, Bremer M, Ferrer-Tur R, et al. Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material. J Extracell Vesicles 2019; 8(1): 1587567.
[http://dx.doi.org/10.1080/20013078.2019.1587567] [PMID: 30949308]
[123]
He M, Crow J, Roth M, Zeng Y, Godwin AK. Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology. Lab Chip 2014; 14(19): 3773-80.
[http://dx.doi.org/10.1039/C4LC00662C] [PMID: 25099143]
[124]
Zhu X, Shen H, Yin X, et al. Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res 2019; 38(1): 81.
[http://dx.doi.org/10.1186/s13046-019-1095-1] [PMID: 30770776]
[125]
Sivakumaran M, Platt M. Tunable resistive pulse sensing: Potential applications in nanomedicine. Nanomedicine 2016; 11(16): 2197-214.
[http://dx.doi.org/10.2217/nnm-2016-0097] [PMID: 27480794]
[126]
Logozzi M, Di Raimo R, Mizzoni D, Fais S. Immunocapture-based ELISA to characterize and quantify exosomes in both cell culture supernatants and body fluids. Methods Enzymol 2020; 645: 155-80.
[http://dx.doi.org/10.1016/bs.mie.2020.06.011] [PMID: 33565970]
[127]
Lyu TS, Ahn Y, Im YJ, et al. The characterization of exosomes from fibrosarcoma cell and the useful usage of dynamic light scattering (DLS) for their evaluation. PLoS One 2021; 16(1): e0231994.
[http://dx.doi.org/10.1371/journal.pone.0231994] [PMID: 33497388]
[128]
Tertel T, Görgens A, Giebel B. Analysis of individual extracellular vesicles by imaging flow cytometry. Methods Enzymol 2020; 645: 55-78.
[http://dx.doi.org/10.1016/bs.mie.2020.05.013] [PMID: 33565978]
[129]
Kim DH, Lee HY, Kim H, Kim H, Lee YS, Park SB. Quantitative evaluation of HiCore resin for the nonspecific binding of proteins by on-bead colorimetric assay. J Comb Chem 2006; 8(3): 280-5.
[http://dx.doi.org/10.1021/cc0501413] [PMID: 16676994]
[130]
Stuffers S, Sem Wegner C, Stenmark H, Brech A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 2009; 10(7): 925-37.
[http://dx.doi.org/10.1111/j.1600-0854.2009.00920.x] [PMID: 19490536]
[131]
Lee Y, EL Andaloussi S, Wood MJA. Exosomes and microvesicles: Extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 2012; 21(R1): R125-34.
[http://dx.doi.org/10.1093/hmg/dds317] [PMID: 22872698]
[132]
Tvall J, Hill AF, Hochberg F. Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the international society for extracellular vesicles. J Extracell Vesicles 2014; 3: 26913.
[133]
Methods of intensification of mass transfer processes in heterophase media. International Scientific Conference pharmaceutical and medical biotechnology
[134]
Butler TAJ, Paul JW, Chan EC, Smith R, Tolosa JM. Misleading westerns: Common quantification mistakes in western blot densitometry and proposed corrective measures. BioMed Res Int 2019; 2019: 1-15.
[http://dx.doi.org/10.1155/2019/5214821] [PMID: 30800670]
[135]
Watson DC, Yung BC, Bergamaschi C, et al. Scalable, cGMP- compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes. J Extracell Vesicles 2018; 7(1): 1442088.
[http://dx.doi.org/10.1080/20013078.2018.1442088] [PMID: 29535850]
[136]
Kowal J, Arras G, Colombo M, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA 2016; 113(8): E968-77.
[http://dx.doi.org/10.1073/pnas.1521230113] [PMID: 26858453]
[137]
Lai RC, Tan SS, Yeo RWY, et al. MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. J Extracell Vesicles 2016; 5(1): 29828.
[http://dx.doi.org/10.3402/jev.v5.29828] [PMID: 26928672]
[138]
Batrakova EV, Kim MS. Development and regulation of exosome-based therapy products. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016; 8(5): 744-57.
[http://dx.doi.org/10.1002/wnan.1395] [PMID: 26888041]
[139]
Patel S, Mehta-Damani A, Shu H, Le Pecq JB. An analysis of variability in the manufacturing of dexosomes: Implications for development of an autologous therapy. Biotechnol Bioeng 2005; 92(2): 238-49.
[http://dx.doi.org/10.1002/bit.20596] [PMID: 16037986]
[140]
Pacienza N, Lee RH, Bae EH, et al. In vitro macrophage assay predicts the in vivo anti-inflammatory potential of exosomes from human mesenchymal stromal cells. Mol Ther Methods Clin Dev 2019; 13: 67-76.
[http://dx.doi.org/10.1016/j.omtm.2018.12.003] [PMID: 30719485]
[141]
Blazquez R, Sanchez-Margallo FM, de la Rosa O, et al. Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol 2014; 5: 556.
[http://dx.doi.org/10.3389/fimmu.2014.00556] [PMID: 25414703]
[142]
Gouveia de Andrade AV, Bertolino G, Riewaldt J, et al. Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation. Stem Cells Dev 2015; 24(11): 1374-6.
[http://dx.doi.org/10.1089/scd.2014.0563] [PMID: 25779336]
[143]
Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA 2010; 107(14): 6328-33.
[http://dx.doi.org/10.1073/pnas.0914843107] [PMID: 20304794]
[144]
Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010; 285(23): 17442-52.
[http://dx.doi.org/10.1074/jbc.M110.107821] [PMID: 20353945]
[145]
Katsuda T, Ochiya T. Molecular signatures of mesenchymal stem cell-derived extracellular vesicle-mediated tissue repair. Stem Cell Res Ther 2015; 6(1): 212.
[http://dx.doi.org/10.1186/s13287-015-0214-y] [PMID: 26560482]
[146]
Gong M, Yu B, Wang J, et al. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget 2017; 8(28): 45200-12.
[http://dx.doi.org/10.18632/oncotarget.16778] [PMID: 28423355]
[147]
Pakravan K, Babashah S, Sadeghizadeh M, et al. MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cell Oncol 2017; 40(5): 457-70.
[http://dx.doi.org/10.1007/s13402-017-0335-7] [PMID: 28741069]
[148]
Song Y, Dou H, Li X, et al. Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1β-primed mesenchymal stem cells against sepsis. Stem Cells 2017; 35(5): 1208-21.
[http://dx.doi.org/10.1002/stem.2564] [PMID: 28090688]
[149]
Qu Y, Zhang Q, Cai X, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med 2017; 21(10): 2491-502.
[http://dx.doi.org/10.1111/jcmm.13170] [PMID: 28382720]
[150]
Lou G, Yang Y, Liu F, et al. MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis. J Cell Mol Med 2017; 21(11): 2963-73.
[http://dx.doi.org/10.1111/jcmm.13208] [PMID: 28544786]
[151]
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-beta/smad2 pathway during wound healing. Stem Cells Transl Med 2016; 5(10): 1425-39.
[http://dx.doi.org/10.5966/sctm.2015-0367] [PMID: 27388239]
[152]
Mebarki M, Abadie C, Larghero J, Cras A. Human umbilical cord-derived mesenchymal stem/stromal cells: a promising candidate for the development of advanced therapy medicinal products. Stem Cell Res Ther 2021; 12(1): 152.
[153]
Mendicino M, Bailey AM, Wonnacott K, Puri RK, Bauer SR. MSC-based product characterization for clinical trials: an FDA perspective. Cell Stem Cell 2014; 14(2): 141-5.
[http://dx.doi.org/10.1016/j.stem.2014.01.013] [PMID: 24506881]

Rights & Permissions Print Cite
Article Metrics
19
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy