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http://dx.doi.org/10.5483/BMBRep.2022.55.2.182

Multiplexed targeting of microRNA in stem cell-derived extracellular vesicles for regenerative medicine  

Song, Byeong-Wook (Institute for Bio-Medical Convergence, Catholic Kwandong University International St. Mary's Hospital)
Oh, Sekyung (Department of Medical Science, College of Medicine, Catholic Kwandong University)
Chang, Woochul (Department of Biology Education, College of Education, Pusan National University)
Publication Information
BMB Reports / v.55, no.2, 2022 , pp. 65-71 More about this Journal
Abstract
Regenerative medicine is a research field that develops methods to restore damaged cell or tissue function by regeneration, repair or replacement. Stem cells are the raw material of the body that is ultimately used from the point of view of regenerative medicine, and stem cell therapy uses cells themselves or their derivatives to promote responses to diseases and dysfunctions, the ultimate goal of regenerative medicine. Stem cell-derived extracellular vesicles (EVs) are recognized as an attractive source because they can enrich exogenous microRNAs (miRNAs) by targeting pathological recipient cells for disease therapy and can overcome the obstacles faced by current cell therapy agents. However, there are some limitations that need to be addressed before using miRNA-enriched EVs derived from stem cells for multiplexed therapeutic targeting in many diseases. Here, we review various roles on miRNA-based stem cell EVs that can induce effective and stable functional improvement of stem cell-derived EVs. In addition, we introduce and review the implications of several miRNA-enriched EV therapies improved by multiplexed targeting in diseases involving the circulatory system and nervous system. This systemic review may offer potential roles for stem cell-derived therapeutics with multiplexed targeting.
Keywords
Extracellular vesicle; MicroRNA; Regenerative medicine; Stem cell;
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1 Kurtz A (2008) Mesenchymal stem cell delivery routes and fate. Int J Stem Cells 1, 1-7   DOI
2 Hu C, Zhao L, Zhang L, Bao Q and Li L (2020) Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury. Stem Cell Res Ther 11, 377   DOI
3 Kim D, Chang HR and Baek D (2017) Rules for functional microRNA targeting. BMB Rep 50, 554-559   DOI
4 Song BW, Lee CY, Kim R et al (2021) Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts. Exp Mol Med 53, 695-708   DOI
5 Crescitelli R, Lasser C, Szabo TG et al (2013) Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles 2, 20677   DOI
6 Jeppesen DK, Fenix AM, Franklin JL et al (2019) Reassessment of exosome composition. Cell 177, 428-445.e18   DOI
7 O'Brien K, Breyne K, Ughetto S, Laurent LC and Breakefield XO (2020) RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol 21, 585-606   DOI
8 Kim HS, Choi DY, Yun SJ et al (2012) Proteomic analysis of microvesicles derived from human mesenchymal stem cells. J Proteome Res 11, 839-849   DOI
9 de la Cuesta F, Passalacqua I, Rodor J, Bhushan R, Denby L and Baker AH (2019) Extracellular vesicle cross-talk between pulmonary artery smooth muscle cells and endothelium during excessive TGF-β signalling: implications for PAH vascular remodelling. Cell Commun Signal 17, 143   DOI
10 Zhang X, Jiang Y, Huang Q et al (2021) Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia. Stem Cell Res Ther 12, 403   DOI
11 Lou G, Song X, Yang F et al (2015) Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol 8, 122   DOI
12 Izarra A, Moscoso I, Levent E et al (2014) miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction. Stem Cell Rep 3, 1029-1042   DOI
13 Rader DJ and Parmacek MS (2012) Secreted miRNAs suppress atherogenesis. Nat Cell Biol 14, 233-235   DOI
14 Usman WM, Pham TC, Kwok YY et al (2018) Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun 9, 2359   DOI
15 Lamichhane TN, Jeyaram A, Patel DB et al (2016) Oncogene knockdown via active loading of small RNAs into extracellular vesicles by sonication. Cell Mol Bioeng 9, 315-324   DOI
16 Liang G, Zhu Y, Ali DJ et al (2020) Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J Nanobiotechnology 18, 10   DOI
17 Munir J, Yoon JK and Ryu S (2020) Therapeutic miRNA-enriched extracellular vesicles: current approaches and future prospects. Cells 9, 2271   DOI
18 Zhang D, Lee H, Zhu Z, Minhas JK and Jin Y (2017) Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 312, L110-L121   DOI
19 Pan W, Xu X, Zhang M, Song X (2021) Human urine-derived stem cell-derived exosomal miR-21-5p promotes neurogenesis to attenuate Rett syndrome via the EPha4/TEK axis. Lab Invest 101, 824-836   DOI
20 Peng Y, Zhao JL, Peng ZY, Xu WF and Yu GL (2020) Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2. Cell Death Dis 11, 317   DOI
21 Huang L, Fu C, Xiong F, He C and Wei Q (2021) Stem cell therapy for spinal cord injury. Cell Transplant 30, 963689721989266
22 Toma C, Pittenger MF, Cahill KS, Byrne BJ and Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105, 93-98   DOI
23 Wei Z, Batagov AO, Schinelli S et al (2017) Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat Commun 8, 1145   DOI
24 Mao AS and Mooney DJ (2015) Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci U S A 112, 14452-14459   DOI
25 Song BW and Hwang KC (2019) Developmental strategy of stem cell therapy for improving clinically-hostile environment. Ann Stem Cell Res Ther 3, 1033
26 Salazar-Noratto GE, Luo G, Denoeud C et al (2019) Understanding and leveraging cell metabolism to enhance mesenchymal stem cell transplantation survival in tissue engineering and regenerative medicine applications. Stem Cells 38, 22-33   DOI
27 Prockop DJ, Brenner M, Fibbe WE et al (2010) Defining the risks of mesenchymal stromal cell therapy. Cytotherapy 12, 576-578   DOI
28 McGinley LM, McMahon J, Stocca A et al (2013) Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression. Hum Gene Ther 24, 840-851   DOI
29 Makarova J, Turchinovich A, Shkurnikov M and Tonevitsky A (2021) Extracellular miRNAs and cell-cell communication: problems and prospects. Trends Biochem Sci 46, 640-651   DOI
30 Thery C, Witwer KW, Aikawa et al (2018) 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 7, 1535750   DOI
31 Baglio SR, Pegtel DM and Baldini N (2012) Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front Physiol 6, 359   DOI
32 Dykxhoorn DM, Novina CD and Sharp PA (2003) Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 4, 457-467   DOI
33 Jeyaram A, Lamichhane TN, Wang S et al (2020) Enhanced loading of functional miRNA cargo via pH gradient modification of extracellular vesicles. Mol Ther 28, 975-985   DOI
34 Huang JH, Xu Y, Yin XM and Lin FY (2020) Exosomes derived from miR-126-modified MSCs promote angiogenesis and neurogenesis and attenuate apoptosis after spinal cord injury in rats. Neuroscience 424, 133-145   DOI
35 Doyle LM and Wang MZ (2019) Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells 8, 727   DOI
36 Lai RC, Tan SS, Teh BJ et al (2012) Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome. Int J Proteomics 2012, 971907   DOI
37 Chen L, Wang Y, Li S et al (2020) Exosomes derived from GDNF-modified human adipose mesenchymal stem cells ameliorate peritubular capillary loss in tubulointerstitial fibrosis by activating the SIRT1/eNOS signaling pathway. Theranostics 10, 9425-9442   DOI
38 Friedman RC, Farh KK, Burge CB and Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19, 92-105   DOI
39 Morel L, Regan M, Higashimori H et al (2013) Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1. J Biol Chem 288, 7105-7116   DOI
40 Ferguson SW, Wang J, Lee CJ et al (2018) The microRNA regulatory landscape of MSC-derived exosomes: a systems view. Sci Rep 8, 1419   DOI
41 Ying W, Riopel M, Bandyopadhyay G et al (2017) Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 171, 372-384.e12   DOI
42 Yu T, Zhao C, Hou S, Zhou W, Wang B and Chen Y (2019) Exosomes secreted from miRNA-29b-modified mesenchymal stem cells repaired spinal cord injury in rats. Braz J Med Biol Res 52, e8735   DOI
43 Fu S, Wang Y, Xia X and Zheng JC (2020) Exosome engineering: current progress in cargo loading and targeted delivery. NanoImpact 20, 100261   DOI
44 Naseri Z, Oskuee RK, Forouzandeh-Moghadam M and Jaafari MR (2020) Delivery of LNA-antimiR-142-3p by mesenchymal stem cells-derived exosomes to breast cancer stem cells reduces tumorigenicity. Stem Cell Rev Rep 16, 541-556   DOI
45 Hu J, Zeng L, Huang J, Wang G and Lu H (2015) miR-126 promotes angiogenesis and attenuates inflammation after contusion spinal cord injury in rats. Brain Res 1608, 191-202   DOI
46 Makarova JA, Shkurnikov MU, Wicklein D et al (2016) Intracellular and extracellular microRNA: an update on localization and biological role. Prog Histochem Cytochem 51, 33-49   DOI
47 Stoltz JF, de Isla N, Li YP et al (2015) Stem cells and regenerative medicine: myth or reality of the 21th century. Stem Cells Int 2015, 734731   DOI
48 Zhou J, Li YS, Nguyen P et al (2013) Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress. Circ Res 113, 40-51   DOI
49 Volarevic V, Markovic BS, Gazdic M et al (2018) Ethical and safety issues of stem cell-based therapy. Int J Med Sci 15, 36-45   DOI
50 Chia YC, Anjum CE, Yee HR et al (2020) Stem cell therapy for neurodegenerative diseases: how do stem cells bypass the blood-brain barrier and home to the brain? Stem Cells Int 2020, 8889061