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Current Stem Cell Research & Therapy

Editor-in-Chief

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

Review Article

Exosomal-microRNAs Improve Islet Cell Survival and Function In Islet Transplantation

Author(s): Qiu Minhua, Feng Bingzheng, Xu Zhiran, Zhang Yingying, Yang Yuwei, Zhang Ting, Chen Jibing* and Gao Hongjun*

Volume 19, Issue 5, 2024

Published on: 01 June, 2023

Page: [669 - 677] Pages: 9

DOI: 10.2174/1574888X18666230510105947

Price: $65

Abstract

Exosomal-microRNAs (Exo-miRNAs) are key regulators of islet cell function, including insulin expression, processing, and secretion. Exo-miRNAs have a significant impact on the outcomes of islet transplantation as biomarkers for evaluating islet cell function and survival. Furthermore, they have been linked to vascular remodeling and immune regulation following islet transplantation. Mesenchymal stem cell-derived exosomes have been shown in preliminary studies to improve islet cell viability and function when injected or transplanted into mice. Overall, Exo-miRNAs have emerged as novel agents for improving islet transplantation success rates. The role of islet-derived Exo-miRNAs and mesenchymal stem cells-derived Exo-miRNAs as biomarkers and immunomodulators in islet regeneration, as well as their role in improving islet cell viability and function in islet transplantation, are discussed in this review.

Graphical Abstract

[1]
Rickels MR, Robertson RP. Pancreatic islet transplantation in humans: Recent progress and future directions. Endocr Rev 2019; 40(2): 631-68.
[http://dx.doi.org/10.1210/er.2018-00154] [PMID: 30541144]
[2]
Xie M, Xiong W, She Z, et al. Immunoregulatory effects of stem cell-derived extracellular vesicles on immune cells. Front Immunol 2020; 11: 13.
[http://dx.doi.org/10.3389/fimmu.2020.00013] [PMID: 32117221]
[3]
Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA 2006; 103(11): 4034-9.
[http://dx.doi.org/10.1073/pnas.0510928103] [PMID: 16495412]
[4]
Nicolas FE, Pais H, Schwach F, et al. Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140. RNA 2008; 14(12): 2513-20.
[http://dx.doi.org/10.1261/rna.1221108] [PMID: 18945805]
[5]
Dahiya N, Sherman-Baust CA, Wang TL, et al. MicroRNA expression and identification of putative miRNA targets in ovarian cancer. PLoS One 2008; 3(6): e2436.
[http://dx.doi.org/10.1371/journal.pone.0002436] [PMID: 18560586]
[6]
Toti F, Bayle F, Berney T, et al. Studies of circulating microparticle release in peripheral blood after pancreatic islet transplantation. Transplant Proc 2011; 43(9): 3241-5.
[http://dx.doi.org/10.1016/j.transproceed.2011.10.024] [PMID: 22099767]
[7]
Vallabhajosyula P, Korutla L, Habertheuer A, et al. Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue. J Clin Invest 2017; 127(4): 1375-91.
[http://dx.doi.org/10.1172/JCI87993] [PMID: 28319051]
[8]
Korutla L, Rickels MR, Hu RW, et al. Noninvasive diagnosis of recurrent autoimmune type 1 diabetes after islet cell transplantation. Am J Transplant 2019; 19(6): 1852-8.
[http://dx.doi.org/10.1111/ajt.15322] [PMID: 30801971]
[9]
Saravanan PB, Vasu S, Yoshimatsu G, et al. Differential expression and release of exosomal miRNAs by human islets under inflammatory and hypoxic stress. Diabetologia 2019; 62(10): 1901-14.
[http://dx.doi.org/10.1007/s00125-019-4950-x] [PMID: 31372667]
[10]
Krishnan P, Syed F, Jiyun Kang N, Mirmira RG, Evans-Molina C. Profiling of RNAs from human islet-derived exosomes in a model of type 1 diabetes. Int J Mol Sci 2019; 20(23): 5903.
[http://dx.doi.org/10.3390/ijms20235903] [PMID: 31775218]
[11]
Vasu S, Kumano K, Darden CM, Rahman I, Lawrence MC, Naziruddin B. MicroRNA signatures as future biomarkers for diagnosis of diabetes states. Cells 2019; 8(12): 1533.
[http://dx.doi.org/10.3390/cells8121533] [PMID: 31795194]
[12]
Steinman RM. Decisions about dendritic cells: Past, present, and future. Annu Rev Immunol 2012; 30(1): 1-22.
[http://dx.doi.org/10.1146/annurev-immunol-100311-102839] [PMID: 22136168]
[13]
Garcia-Contreras M, Brooks RW, Boccuzzi L, Robbins PD, Ricordi C. Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus. Eur Rev Med Pharmacol Sci 2017; 21(12): 2940-56.
[PMID: 28682421]
[14]
Pileggi A, Klein D, Fotino C, et al. MicroRNAs in islet immunobiology and transplantation. Immunol Res 2013; 57(1-3): 185-96.
[http://dx.doi.org/10.1007/s12026-013-8436-5] [PMID: 24242759]
[15]
Tang C, Koulajian K, Schuiki I, et al. Glucose-induced beta cell dysfunction in vivo in rats: Link between oxidative stress and endoplasmic reticulum stress. Diabetologia 2012; 55(5): 1366-79.
[http://dx.doi.org/10.1007/s00125-012-2474-8] [PMID: 22396011]
[16]
Tong L, Yuan Y, Wu S. Therapeutic microRNAs targeting the NF-kappa B signaling circuits of cancers. Adv Drug Deliv Rev 2015; 81: 1-15.
[http://dx.doi.org/10.1016/j.addr.2014.09.004] [PMID: 25220353]
[17]
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]
[18]
Favaro E, Carpanetto A, Caorsi C, et al. Human mesenchymal stem cells and derived extracellular vesicles induce regulatory dendritic cells in type 1 diabetic patients. Diabetologia 2016; 59(2): 325-33.
[http://dx.doi.org/10.1007/s00125-015-3808-0] [PMID: 26592240]
[19]
Cappellesso-Fleury S, Puissant-Lubrano B, Apoil PA, et al. Human fibroblasts share immunosuppressive properties with bone marrow mesenchymal stem cells. J Clin Immunol 2010; 30(4): 607-19.
[http://dx.doi.org/10.1007/s10875-010-9415-4] [PMID: 20405178]
[20]
Shigemoto-Kuroda T, Oh JY, Kim D, et al. MSC-derived extracellular vesicles attenuate immune responses in two autoimmune murine models: Type 1 diabetes and uveoretinitis. Stem Cell Reports 2017; 8(5): 1214-25.
[http://dx.doi.org/10.1016/j.stemcr.2017.04.008] [PMID: 28494937]
[21]
Nojehdehi S, Soudi S, Hesampour A, Rasouli S, Soleimani M, Hashemi SM. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes. J Cell Biochem 2018; 119(11): 9433-43.
[http://dx.doi.org/10.1002/jcb.27260] [PMID: 30074271]
[22]
Chamberlain CS, Kink JA, Wildenauer LA, et al. Exosome-educated macrophages and exosomes differentially improve ligament healing. Stem Cells 2021; 39(1): 55-61.
[http://dx.doi.org/10.1002/stem.3291] [PMID: 33141458]
[23]
Liu W, Yu M, Xie D, et al. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res Ther 2020; 11(1): 259.
[http://dx.doi.org/10.1186/s13287-020-01756-x] [PMID: 32600435]
[24]
de Souza BM, Bouças AP, Oliveira FS, et al. Effect of co-culture of mesenchymal stem/stromal cells with pancreatic islets on viability and function outcomes: A systematic review and meta-analysis. Islets 2017; 9(2): 30-42.
[http://dx.doi.org/10.1080/19382014.2017.1286434] [PMID: 28151049]
[25]
Chen J, Chen J, Cheng Y, et al. Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation. Stem Cell Res Ther 2020; 11(1): 97.
[http://dx.doi.org/10.1186/s13287-020-01610-0] [PMID: 32127037]
[26]
Zhao H, Guan J, Lee HM, et al. Up-regulated pancreatic tissue microRNA-375 associates with human type 2 diabetes through beta-cell deficit and islet amyloid deposition. Pancreas 2010; 39(6): 843-6.
[http://dx.doi.org/10.1097/MPA.0b013e3181d12613] [PMID: 20467341]
[27]
Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F, Mobarra N. miRNA-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hiPS) cells. Mol Biol Rep 2014; 41(4): 2055-66.
[http://dx.doi.org/10.1007/s11033-014-3054-4] [PMID: 24469711]
[28]
Wen D, Peng Y, Liu D, Weizmann Y, Mahato RI. Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation. J Control Release 2016; 238: 166-75.
[http://dx.doi.org/10.1016/j.jconrel.2016.07.044] [PMID: 27475298]
[29]
Jacovetti C, Jimenez V, Ayuso E, et al. Contribution of intronic miR-338-3p and its hosting gene AATK to compensatory β-cell mass expansion. Mol Endocrinol 2015; 29(5): 693-702.
[http://dx.doi.org/10.1210/me.2014-1299] [PMID: 25751313]
[30]
Tattikota SG, Rathjen T, McAnulty SJ, et al. Argonaute2 mediates compensatory expansion of the pancreatic β cell. Cell Metab 2014; 19(1): 122-34.
[http://dx.doi.org/10.1016/j.cmet.2013.11.015] [PMID: 24361012]
[31]
Tattikota SG, Rathjen T, Hausser J, et al. miR-184 regulates pancreatic β-cell function according to glucose metabolism. J Biol Chem 2015; 290(33): 20284-94.
[http://dx.doi.org/10.1074/jbc.M115.658625] [PMID: 26152724]
[32]
Bao L, Fu X, Si M, et al. MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes. PLoS One 2015; 10(2): e0116067.
[http://dx.doi.org/10.1371/journal.pone.0116067] [PMID: 25658748]
[33]
Bang-Berthelsen CH, Pedersen L, Fløyel T, Hagedorn PH, Gylvin T, Pociot F. Independent component and pathway-based analysis of miRNA-regulated gene expression in a model of type 1 diabetes. BMC Genomics 2011; 12(1): 97.
[http://dx.doi.org/10.1186/1471-2164-12-97] [PMID: 21294859]
[34]
Figliolini F, Cantaluppi V, De Lena M, et al. Isolation, characterization and potential role in beta cell-endothelium cross-talk of extracellular vesicles released from human pancreatic islets. PLoS One 2014; 9(7): e102521.
[http://dx.doi.org/10.1371/journal.pone.0102521] [PMID: 25028931]
[35]
Nonaka T, Wong DTW. Saliva-exosomics in cancer: Molecular characterization of cancer-derived exosomes in saliva. Enzymes 2017; 42: 125-51.
[http://dx.doi.org/10.1016/bs.enz.2017.08.002] [PMID: 29054268]
[36]
Pullen TJ, da Silva Xavier G, Kelsey G, Rutter GA. miR-29a and miR-29b contribute to pancreatic beta-cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol Cell Biol 2011; 31(15): 3182-94.
[http://dx.doi.org/10.1128/MCB.01433-10] [PMID: 21646425]
[37]
Cantaluppi V, Biancone L, Figliolini F, et al. Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis of human pancreatic islets. Cell Transplant 2012; 21(6): 1305-20.
[http://dx.doi.org/10.3727/096368911X627534] [PMID: 22455973]
[38]
Ferguson SW, Nguyen J. Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity. J Control Release 2016; 228: 179-90.
[http://dx.doi.org/10.1016/j.jconrel.2016.02.037] [PMID: 26941033]
[39]
Nie W, Ma X, Yang C, et al. Human mesenchymal-stem-cells-derived exosomes are important in enhancing porcine islet resistance to hypoxia. Xenotransplantation 2018; 25(5): e12405.
[http://dx.doi.org/10.1111/xen.12405] [PMID: 29932262]
[40]
Bandara KV, Michael MZ, Gleadle JM. MicroRNA biogenesis in hypoxia. MicroRNA 2017; 6(2): 80-96.
[http://dx.doi.org/10.2174/2211536606666170313114821] [PMID: 28294076]
[41]
Finnerty JR, Wang WX, Hébert SS, Wilfred BR, Mao G, Nelson PT. The miR-15/107 group of microRNA genes: Evolutionary biology, cellular functions, and roles in human diseases. J Mol Biol 2010; 402(3): 491-509.
[http://dx.doi.org/10.1016/j.jmb.2010.07.051] [PMID: 20678503]
[42]
Poliseno L, Tuccoli A, Mariani L, et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood 2006; 108(9): 3068-71.
[http://dx.doi.org/10.1182/blood-2006-01-012369] [PMID: 16849646]
[43]
Hua Z, Lv Q, Ye W, et al. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 2006; 1(1): e116.
[http://dx.doi.org/10.1371/journal.pone.0000116] [PMID: 17205120]
[44]
Chan LS, Yue PYK, Mak NK, Wong RNS. Role of MicroRNA-214 in ginsenoside-Rg1-induced angiogenesis. Eur J Pharm Sci 2009; 38(4): 370-7.
[http://dx.doi.org/10.1016/j.ejps.2009.08.008] [PMID: 19733659]
[45]
Özcan S. Minireview: MicroRNA function in pancreatic β cells. Mol Endocrinol 2014; 28(12): 1922-33.
[http://dx.doi.org/10.1210/me.2014-1306] [PMID: 25396300]
[46]
Zhao X, Mohan R, Özcan S, Tang X. MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells. J Biol Chem 2012; 287(37): 31155-64.
[http://dx.doi.org/10.1074/jbc.M112.362632] [PMID: 22733810]
[47]
Sebastiani G, Po A, Miele E, et al. MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion. Acta Diabetol 2015; 52(3): 523-30.
[http://dx.doi.org/10.1007/s00592-014-0675-y] [PMID: 25408296]
[48]
Fred RG, Bang-Berthelsen CH, Mandrup-Poulsen T, Grunnet LG, Welsh N. High glucose suppresses human islet insulin biosynthesis by inducing miR-133a leading to decreased polypyrimidine tract binding protein-expression. PLoS One 2010; 5(5): e10843.
[http://dx.doi.org/10.1371/journal.pone.0010843] [PMID: 20520763]
[49]
Chakraborty C, George Priya Doss C, Bandyopadhyay S. miRNAs in insulin resistance and diabetes-associated pancreatic cancer: The ‘minute and miracle’ molecule moving as a monitor in the ‘genomic galaxy’. Curr Drug Targets 2013; 14(10): 1110-7.
[http://dx.doi.org/10.2174/13894501113149990182] [PMID: 23834149]
[50]
Roggli E, Britan A, Gattesco S, et al. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells. Diabetes 2010; 59(4): 978-86.
[http://dx.doi.org/10.2337/db09-0881] [PMID: 20086228]
[51]
Nesca V, Guay C, Jacovetti C, et al. Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes. Diabetologia 2013; 56(10): 2203-12.
[http://dx.doi.org/10.1007/s00125-013-2993-y] [PMID: 23842730]
[52]
Bagge A, Dahmcke C, Dalgaard L. Syntaxin-1a is a direct target of miR-29a in insulin-producing β-cells. Horm Metab Res 2013; 45(6): 463-6.
[http://dx.doi.org/10.1055/s-0032-1333238] [PMID: 23315993]
[53]
Hennessy E, Clynes M, Jeppesen PB, O’Driscoll L. Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells. Biochem Biophys Res Commun 2010; 396(2): 457-62.
[http://dx.doi.org/10.1016/j.bbrc.2010.04.116] [PMID: 20417623]
[54]
Backe MB, Novotny GW, Christensen DP, Grunnet LG, Mandrup-Poulsen T. Altering β-cell number through stable alteration of miR-21 and miR-34a expression. Islets 2014; 6(1): e27754.
[http://dx.doi.org/10.4161/isl.27754] [PMID: 25483877]
[55]
Latreille M, Hausser J, Stützer I, et al. MicroRNA-7a regulates pancreatic β cell function. J Clin Invest 2014; 124(6): 2722-35.
[http://dx.doi.org/10.1172/JCI73066] [PMID: 24789908]
[56]
Vergauwen G, Dhondt B, Van Deun J, et al. Confounding factors of ultrafiltration and protein analysis in extracellular vesicle research. Sci Rep 2017; 7(1): 2704.
[http://dx.doi.org/10.1038/s41598-017-02599-y] [PMID: 28577337]
[57]
Sun Y, Mao Q, Shen C, Wang C, Jia W. Exosomes from β-cells alleviated hyperglycemia and enhanced angiogenesis in islets of streptozotocin-induced diabetic mice. Diabetes Metab Syndr Obes 2019; 12: 2053-64.
[http://dx.doi.org/10.2147/DMSO.S213400] [PMID: 31632115]
[58]
Wijesekara N, Zhang L, Kang MH, et al. miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets. Diabetes 2012; 61(3): 653-8.
[http://dx.doi.org/10.2337/db11-0944] [PMID: 22315319]
[59]
Kang MH, Zhang LH, Wijesekara N, et al. Regulation of ABCA1 protein expression and function in hepatic and pancreatic islet cells by miR-145. Arterioscler Thromb Vasc Biol 2013; 33(12): 2724-32.
[http://dx.doi.org/10.1161/ATVBAHA.113.302004] [PMID: 24135019]
[60]
Street JM, Koritzinsky EH, Glispie DM, Yuen PST. Urine exosome isolation and characterization. Methods Mol Biol 2017; 1641: 413-23.
[http://dx.doi.org/10.1007/978-1-4939-7172-5_23] [PMID: 28748478]
[61]
Yu LL, Zhu J, Liu JX, et al. A comparison of traditional and novel methods for the separation of exosomes from human samples. BioMed Res Int 2018; 2018: 1-9.
[http://dx.doi.org/10.1155/2018/3634563] [PMID: 30148165]
[62]
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]
[63]
Foers AD, Chatfield S, Dagley LF, et al. Enrichment of extracellular vesicles from human synovial fluid using size exclusion chromatography. J Extracell Vesicles 2018; 7(1): 1490145.
[http://dx.doi.org/10.1080/20013078.2018.1490145] [PMID: 29963299]
[64]
La Shu S, Yang Y, Allen CL, et al. Purity and yield of melanoma exosomes are dependent on isolation method. J Extracell Vesicles 2020; 9(1): 1692401.
[http://dx.doi.org/10.1080/20013078.2019.1692401] [PMID: 31807236]
[65]
Karttunen J, Heiskanen M, Navarro-Ferrandis V, et al. Precipitation-based extracellular vesicle isolation from rat plasma co-precipitate vesicle-free microRNAs. J Extracell Vesicles 2019; 8(1): 1555410.
[http://dx.doi.org/10.1080/20013078.2018.1555410] [PMID: 30574280]
[66]
Iliescu F. Vrtačnik D, Neuzil P, Iliescu C. Microfluidic technology for clinical applications of exosomes. Micromachines (Basel) 2019; 10(6): 392.
[http://dx.doi.org/10.3390/mi10060392] [PMID: 31212754]
[67]
Witwer KW, Van Balkom BWM, Bruno S, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles 2019; 8(1): 1609206.
[http://dx.doi.org/10.1080/20013078.2019.1609206] [PMID: 31069028]
[68]
Ayers L, Pink R, Carter DRF, Nieuwland R. Clinical requirements for extracellular vesicle assays. J Extracell Vesicles 2019; 8(1): 1593755.
[http://dx.doi.org/10.1080/20013078.2019.1593755] [PMID: 30949310]
[69]
Shao H, Im H, Castro CM, Breakefield X, Weissleder R, Lee H. New technologies for analysis of extracellular vesicles. Chem Rev 2018; 118(4): 1917-50.
[http://dx.doi.org/10.1021/acs.chemrev.7b00534] [PMID: 29384376]

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