Research Progress in Milk-derived Exosomes

LI Ying; CHEN Jingyao; ZHAO Junying; YU Xiaowen; YANG Yihan; HU Jufeng; JIANG Tiemin; CHEN Lijun

doi:10.13386/j.issn1002-0306.2021090317

Volume 43 Issue 22

Nov. 2022

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Science and Technology of Food Industry > 2022 > 43(22): 406-413. > DOI: 10.13386/j.issn1002-0306.2021090317

LI Ying, CHEN Jingyao, ZHAO Junying, et al. Research Progress in Milk-derived Exosomes[J]. Science and Technology of Food Industry, 2022, 43(22): 406−413. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021090317.

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Research Progress in Milk-derived Exosomes

LI Ying^{1, 2,},
CHEN Jingyao²,
ZHAO Junying^{2, 3},
YU Xiaowen^{1, 2},
YANG Yihan^{1, 2},
HU Jufeng^{1, 2},
JIANG Tiemin³,
CHEN Lijun^{1, 2, 3, ,}

1.
College of Food Science, Northeast Agricultural University, Harbin 150030, China
2.
National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Food Co., Ltd., Beijing 100163, China
3.
South Asia Branch of National Engineering Research Center of Dairy Health for Maternal and Child, Guilin University of Technology, Guilin 541006, China

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Received Date: September 26, 2021
Available Online: September 07, 2022

Graphical Abstract

Abstract

Abstract

Milk exosomes are a newly discovered functional vesicles secreted by animal mammary epithelial cells, small vesicles with membrane structure in the diameter of about 30~200 nm, which contain many bioactive substances such as proteins, lipids, and nucleic acids on the surface and inside the membrane. Recent studies have found exosomes with biological functions such as mediating cell communication, promoting cell proliferation, and participating in immune responses. Exosomes can be isolated from the emulsion by centrifugation, chemical, immunoaffinity and identified their morphology, size, specific substances. This article reviews the biological function, three omics studies, separation and identification methods, and aims to provide scientific reference for the research and development of milk source exosomes.
- milk derived exosomes,
- biological function,
- multi-omics study,
- separation and identification

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References (69)

References

[1]	LI L, LI C, WANG S, et al. Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype[J]. Cancer Research,2016,76(7):1770−1780. doi: 10.1158/0008-5472.CAN-15-1625
[2]	HOSHINO A, COSTA S B, SHEN T L, et al. Tumour exosome integrins determine organotropic metastasis[J]. Nature,2015,527(7578):329−335. doi: 10.1038/nature15756
[3]	THERY C, AMIGORENA S, RAPOSO G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids[J]. Current Protocols in Cell Biology,2006,30(1):3.22.
[4]	ZHANG J, LI S, LI L, et al. Exosome and exosomal microRNA: trafficking, sorting, and function[J]. Genomics, Proteomics & Bioinformatics,2015,13(1):17−24.
[5]	HARDING C, STAHL H P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes[J]. Journal of Cell Biology,1983,97(2):329−339. doi: 10.1083/jcb.97.2.329
[6]	PAN B T, JOHNSTONE R M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor[J]. Cell,1983,33(3):967−978. doi: 10.1016/0092-8674(83)90040-5
[7]	JOHNSTONE R M, ADAM M, HAMMOND J R, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)[J]. Journal of Biological Chemistry,1987,262(19):9412−9420. doi: 10.1016/S0021-9258(18)48095-7
[8]	VALADI H, EKSTRŐM K, BOSSIOS A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells[J]. Nature Cell Biology,2007,9(6):654−659. doi: 10.1038/ncb1596
[9]	COLITTI M, SGORLON S, STEFANON B. Exosome cargo in milk as a potential marker of cow health[J]. J Dairy Res,2020,87(S1):1−5. doi: 10.1017/S0022029920000679
[10]	VAN D P E, BOING A N, HARRISON P, et al. Classification, functions, and clinical relevance of extracellular vesicles[J]. Pharmacological Reviews,2012,64(3):676−705. doi: 10.1124/pr.112.005983
[11]	KUMEDA, NAHOKO, OGAWA, et al. Characterization of membrane integrity and morphological stability of human salivary exosomes[J]. Biological and Pharmaceutical Bulletin,2017,40(8):1183−1191. doi: 10.1248/bpb.b16-00891
[12]	SUGIMACHI K, MATSUMURA T, HIRATA H, et al. Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation[J]. British Journal of Cancer,2015,112(3):532−538. doi: 10.1038/bjc.2014.621
[13]	NILSSON J, SKOG J, NORDSTRAND A, et al. Prostate cancer-derived urine exosomes: A novel approach to biomarkers for prostate cancer[J]. British Journal of Cancer,2009,100(10):1603−1607. doi: 10.1038/sj.bjc.6605058
[14]	VASHISHT M, RANI P, ONTERU S K, et al. Curcumin encapsulated in milk exosomes resists human digestion and possesses enhanced intestinal permeability in vitro[J]. Applied Biochemistry and Biotechnology,2017,183(3):993−1007. doi: 10.1007/s12010-017-2478-4
[15]	WOLF T, BAIER S R, ZEMPLENI J. The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells[J]. The Journal of Nutrition,2015,145(10):2201−2206. doi: 10.3945/jn.115.218586
[16]	IZUMI H, TSUDA M, SAYO Y, et al. Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages[J]. Journal of Dairy Science,2015,98(5):2920−2933. doi: 10.3168/jds.2014-9076
[17]	权素玉, 南雪梅, 蒋林树, 等. 动物外泌体的生物学功能研究进展[J]. 动物营养学报,2018,30(12):4786−4791. [QUAN S Y, NAN X M, JIANG L S, et al. Advances in biological functions of animal exosomes[J]. Chinese Journal of Animal Nutrition,2018,30(12):4786−4791. doi: 10.3969/j.issn.1006-267x.2018.12.003
[18]	CAROLINA D, GOREHAM R V, BECH S, et al. “Exosomics”—a review of biophysics, biology and biochemistry of exosomes with a focus on human breast milk[J]. Frontiers in Genetics,2018,9:92. doi: 10.3389/fgene.2018.00092
[19]	GONZALEZ B M, LU B, HAN X, et al. Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT)[J]. Journal of Proteome Research,2009,8(3):1304−1314. doi: 10.1021/pr800658c
[20]	LILLA T, PETRA M, TAMAS G, et al. Proteomic characterization of thymocyte-derived microvesicles and apoptotic bodies in BALB/c mice[J]. Journal of Proteomics,2011,74(10):2025−2033. doi: 10.1016/j.jprot.2011.05.023
[21]	MOHAMMED H R, EMINE B, GOUDA K H, et al. Exosomes: From garbage bins to promising therapeutic targets[J]. International Journal of Molecular Sciences,2017,18(3):538. doi: 10.3390/ijms18030538
[22]	MATHIEU M, NEVO N, JOUVE M, et al. Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9[J]. Nature Communications,2021,12(1):1−18. doi: 10.1038/s41467-020-20314-w
[23]	SKOTLAND T, HESSVIK N P, SANDVIG K, et al. Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology[J]. Journal of Lipid Research,2019,60(1):9−18. doi: 10.1194/jlr.R084343
[24]	GU Y, LI M, WANG T, et al. Lactation-related microRNA expression profiles of porcine breast milk exosomes[J]. Plos One,2012,7(8):e43691. doi: 10.1371/journal.pone.0043691
[25]	LIAO Y L, DU X G, LI J, et al. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells[J]. Molecular Nutrition & Food Research,2017:1700082.
[26]	LASSER C, ALIKHANI V S, EKSTROM K, et al. Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages[J]. Journal of translational medicine,2011,9(1):1−8. doi: 10.1186/1479-5876-9-1
[27]	高海娜. 牦牛乳外泌体miRNA缓解小肠上皮细胞缺氧损伤的作用机制[D]. 兰州: 甘肃农业大学, 2019 GAO H N. Study of the mechanism for yak milk exosomal mi RNAs in alleviating hypoxia injury of intestinal epithelial cells[D]. Lanzhou: Gansu Agricultural University, 2019.
[28]	XU R J. Development of the newborn GI tract and its relation to colostrum/milk intake: A review[J]. Reproduction, Fertility and Development,1996,8(1):35−48. doi: 10.1071/RD9960035
[29]	CHEN T, XIE M Y, SUN J J, et al. Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells[J]. Scientific Reports,2016,6(1):1−12. doi: 10.1038/s41598-016-0001-8
[30]	XIE M Y, CHEN T, XI Q Y, et al. Porcine milk exosome miRNAs protect intestinal epithelial cells against deoxynivalenol-induced damage[J]. Biochemical Pharmacology,2020,175(1):113898.
[31]	HOCK A, MIYAKE H, LI B, et al. Breast milk-derived exosomes promote intestinal epithelial cell growth[J]. Journal of Pediatric Surgery,2017,52(5):755−759. doi: 10.1016/j.jpedsurg.2017.01.032
[32]	GAO R, ZHANG R, QIAN T, et al. A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury[J]. Pediatric Surgery International,2019,35(12):1363−1368. doi: 10.1007/s00383-019-04562-6
[33]	ADMYRE C, JOHANSSON S M, QAZI K R, et al. Exosomes with immune modulatory features are present in human breast milk[J]. The Journal of Immunology,2007,179(3):1969−1978. doi: 10.4049/jimmunol.179.3.1969
[34]	MELNIK B C, JOHN S, SCHMITZ G. Milk: An exosomal microRNA transmitter promoting thymic regulatory T cell maturation preventing the development of atopy?[J]. Journal of Translational Medicine,2014,12(1):43−43. doi: 10.1186/1479-5876-12-43
[35]	ZHOU Q, LI M, WANG X, et al. Immune-related MicroRNAs are Abundant in breast milk exosomes[J]. International Journal of Biological Sciences,2012,8(1):118−123. doi: 10.7150/ijbs.8.118
[36]	KOSAKA N, IZUMI H, SEKINE K, et al. microRNA as a new immune-regulatory agent in breast milk[J]. Silence,2010,1(1):1−8. doi: 10.1186/1758-907X-1-1
[37]	张顺华. 猪不同泌乳期乳汁Exosome中microRNA转录组的鉴定和表达谱分析[D]. 成都: 四川农业大学, 2013 ZHANG S H. Lactation-related microRNA expression profiles of porcine breast milk exosomes[D]. Chengdu: Sichuan Agricultural University, 2013.
[38]	GREENING D W, RONG X, HONG J, et al. A protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods[J]. Methods Mol Biol, 2015, 1295: 179-209.
[39]	罗靖莹, 贺宏丽, 郭阳, 等. 差速离心、密度梯度离心、超滤离心技术在骨髓间充质干细胞外泌体提取中的应用对比观察[J]. 山东医药,2019,59(12):48−52. [LUO J Y, HE H L, GUO Y, et al. Comparison of differential centrifugation, density gradient centrifugation, and ultrafiltration of centrifugation in extraction of exosomes from bone marrow mesenchymal stem cells[J]. Shandong Medicine,2019,59(12):48−52. doi: 10.3969/j.issn.1002-266X.2019.12.013
[40]	TIMOTHY A R, JOHN D L, BRIAN J N, et al. Bovine milk exosome proteome[J]. Journal of Proteomics,2012,75(5):1486−1492. doi: 10.1016/j.jprot.2011.11.017
[41]	GUPTA S, RAWAT S, ARORA V, et al. An improvised one-step sucrose cushion ultracentrifugation method for exosome isolation from culture supernatants of mesenchymal stem cells[J]. Stem Cell Research & Therapy,2018,9(1):1−11.
[42]	TANIA S M, JOSE C, ILKA M R, et al. Exosome isolation from distinct biofluids using precipitation and column-based approaches[J]. Plos One,2018,13(6):e0198820. doi: 10.1371/journal.pone.0198820
[43]	INAS H, CAI J, DREWRY M D, et al. A Comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents[J]. PLoS One,2017,12(1):e0170628. doi: 10.1371/journal.pone.0170628
[44]	FITZGERALD J, LEONARD P, DARCY E, et al. Immunoaffinity chromatography: concepts and applications[J]. Protein Chromatography,2017:27−51.
[45]	BLANS K, HANSEN M S, SORNESEN L V, et al. Pellet-free isolation of human and bovine milk extracellular vesicles by size-exclusion chromatography[J]. Journal of Extracellular Vesicles,2017,6(1):1294340. doi: 10.1080/20013078.2017.1294340
[46]	VASWANI K, KOH Y Q, ALMUGHLLIQ F B, et al. A method for the isolation and enrichment of purified bovine milk exosomes[J]. Reproductive Biology,2017,17(4):341−348. doi: 10.1016/j.repbio.2017.09.007
[47]	LIGA A, VLIEGENTHART A D B, OOSTHUYZEN W, et al. Exosome isolation: A microfluidic road-map[J]. Lab on a Chip,2015,15(11):2388−2394. doi: 10.1039/C5LC00240K
[48]	AUGUSTSSON P, KARLSEN J T, SU H W, et al. Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping[J]. Nature Communications,2016(7):11556.
[49]	HE M, CROW J, ROTH M, et al. Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology[J]. Lab Chip,2014,14(19):3773−3780. doi: 10.1039/C4LC00662C
[50]	YASUI T, YANAGIDA T, ITO S, et al. Unveiling massive numbers of cancer-related urinary-microRNA candidates via nanowires[J]. Science Advances,2017,3(12):e1701133. doi: 10.1126/sciadv.1701133
[51]	YANG X X, SUN C, WANG L, et al. New insight into isolation, identification techniques and medical applications of exosomes[J]. Journal of Controlled Release,2019,308:119−129. doi: 10.1016/j.jconrel.2019.07.021
[52]	TRAMS E G, LAUTER C J, JR S N, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles[J]. Biochimica et Biophysica Acta (BBA) -Biomembranes,1981,645(1):63−70. doi: 10.1016/0005-2736(81)90512-5
[53]	凌妍, 钟娇丽, 唐晓山, 等. 扫描电子显微镜的工作原理及应用[J]. 山东化工,2018,47(9):78−79. [LING Y, ZHONG J L, TANG S S, et al. The principle and application of scanning electron microscope[J]. Shandong Chemical Industry,2018,47(9):78−79. doi: 10.3969/j.issn.1008-021X.2018.09.033
[54]	TATISCHEFF I, LARQUET E, JUAN M F-P, et al. Fast characterisation of cell-derived extracellular vesicles by nanoparticles tracking analysis, cryo-electron microscopy, and Raman tweezers microspectroscopy[J]. Journal of Extracellular Vesicles,2012,1(1):19179. doi: 10.3402/jev.v1i0.19179
[55]	SOKOLOVA V, LUDWIG A K, HORNUNG S, et al. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy[J]. Colloids & Surfaces B Biointerfaces,2011,87(1):146−150.
[56]	REBECCA A D, CHRIS G, ALEXANDRA S B, et al. Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis[J]. Nanomedicine:Nanotechnology, Biology and Medicine,2011,7(6):780−788. doi: 10.1016/j.nano.2011.04.003
[57]	SITAR S, KEJZAR A, PAHOVNIK D, et al. Size characterization and quantification of exosomes by asymmetrical-flow field-flow fractionation[J]. Analytical Chemistry,2015,87(18):9225−9233. doi: 10.1021/acs.analchem.5b01636
[58]	MADAMANCHI N R, RUNGE M S. Western blotting[J]. Methods in Molecular Medicine,2001,51(3):245.
[59]	KUGERATSKI F G, HODGE K, LILLA S, et al. Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker[J]. Nature Cell Biology,2021,23(6):631−641. doi: 10.1038/s41556-021-00693-y
[60]	EDWIN V D P, LEONIE D R M, FRANK A W C, et al. Absolute sizing and label-free identification of extracellular vesicles by flow cytometry[J]. Nanomedicine:Nanotechnology, Biology and Medicine,2018,14(3):801−810. doi: 10.1016/j.nano.2017.12.012
[61]	李林. 蛋白质组学的进展[J]. 生物化学与生物物理进展,2000,27(3):227−232. [LI L. Progress in proteomics[J]. Progress in Biochemistry and Biophysics,2000,27(3):227−232. doi: 10.3321/j.issn:1000-3282.2000.03.001
[62]	YANG M, SONG D H, CAO X Y, et al. Comparative proteomic analysis of milk-derived exosomes in human and bovine colostrum and mature milk samples by iTRAQ-coupled LC-MS/MS - ScienceDirect[J]. Food Research International,2017,92(Feb.):17−25.
[63]	范士杰. 不同动物乳源性外泌体分离鉴定及其蛋白质组学分析[D]. 北京: 中国农业科学院, 2020 FAN S J. Isolation, identification and proteomic analysis of milk-derived exosomes which from different animals[D]. Beijing: Chinese Academy of Agricultural, 2020.
[64]	陆姝欢, 杨松, 元英进. 脂质组学在医药研究中的应用[J]. 细胞生物学杂志,2007(2):169−172. [LU S H, YANG S, YUAN Y J. Application of lipidomics in medicine and drug development[J]. Chinese Journal of Cell Biology,2007(2):169−172.
[65]	林金丹, 闫爽. 外泌体在脂肪分化与脂代谢中作用的研究进展[J]. 国际内分泌代谢杂志,2020,40(5):335−339. [LIN J D, YAN S. Progress in the role of exosomes in fat differentiation and lipid metabolism[J]. International Journal of Endocrinology and Metabolism,2020,40(5):335−339.
[66]	RECORD M, CARAYON K, POIROT M, et al. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies[J]. Biochimica et Biophysica Acta,2014,1841(1):108−120. doi: 10.1016/j.bbalip.2013.10.004
[67]	屈良鹄. RNA组学: 后基因组时代的科学前沿[J]. 中国科学(生命科学),2009,39(1):1−2. [QU L H. RNA omics: A scientific frontier in the post-genomic era[J]. Science China(Life Sciences),2009,39(1):1−2.
[68]	CHEN X, CHAO G, LI H, et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products[J]. Cell research,2010,20(10):1128−1137. doi: 10.1038/cr.2010.80
[69]	马韶阳. 牛奶来源外泌体miRNA和circRNA在金黄色葡萄球菌源乳腺炎中的功能研究[D]. 杨凌: 西北农林科技大学, 2020 MA S Y. The functions of mi RNAs and circ RNAs from bovine milk-derived exosomes in mastitis caused by Staphylococcus aureus infection[D]. Yangling: Northwest A&F University, 2020.

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