FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Biochim Open / Purified horse milk exosomes contain an unpredictable small ...
Biochimie open2017; 4; 61-72; doi: 10.1016/j.biopen.2017.02.004

Purified horse milk exosomes contain an unpredictable small number of major proteins.

Abstract: Exosomes are 40-100 nm nanovesicles containing RNA and different proteins. Exosomes containing proteins, lipids, mRNAs, and microRNAs are important in intracellular communication and immune function. Exosomes from different sources are usually obtained by combination of centrifugation and ultracentrifugation and according to published data can contain from a few dozens to thousands of different proteins. Crude exosome preparations from milk of eighteen horses were obtained for the first time using several standard centrifugations. Exosome preparations were additionally purified by FPLC gel filtration. Individual preparations demonstrated different profiles of gel filtration showing well or bad separation of exosome peaks and one or two peaks of co-isolating proteins and their complexes. According to the electron microscopy, well purified exosomes displayed a typical exosome-like size (30-100 nm) and morphology. It was shown that exosomes may have several different biological functions, but detection of their biological functions may vary significantly depending on the presence of exosome contaminating proteins and proteins directly into exosomes. Exosome proteins were identified before and after gel filtration by MALDI MS and MS/MS spectrometry of protein tryptic hydrolyzates derived by SDS PAGE and 2D electrophoresis. The results of protein identification were unexpected: one or two peaks co-isolating proteins after gel-filtration mainly contained kappa-, beta-, alpha-S1-caseins and its precursors, but these proteins were not found in well-purified exosomes. Well-purified exosomes contained from five to eight different major proteins: CD81, CD63 receptors, beta-lactoglobulin and lactadherin were common to all preparations, while actin, butyrophilin, lactoferrin, and xanthine dehydrogenase were found only in some of them. The article describes the morphology and the protein content of major horse milk exosomes for the first time. Our results on the decrease of major protein number identified in exosomal preparations after gel filtration may be important to the studies of biological functions of pure exosomes.
Get Full Text
Publication Date: 2017-03-01 PubMed ID: 29450143PubMed Central: PMC5801828DOI: 10.1016/j.biopen.2017.02.004Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the extraction, purification, and protein content analysis of exosomes found in horse milk, providing an overview of the proteins these nanoparticles contain and highlighting the potential importance of these findings in understanding the biological functions of exosomes.

Research Methodology

  • The study begins by explaining that exosomes are nanovesicles ranging around 40-100 nm in size that carry RNA and various proteins within them.
  • They are critical for intracellular communication and immune function due to the proteins, lipids, mRNAs, and microRNAs they contain.
  • Exosomes are generally acquired through a combination of centrifugation and ultracentrifugation techniques, and are known to contain anywhere from a few dozen to thousands of different proteins, according to previously published data.
  • In this study, initial exosome preparations were obtained from the milk of eighteen horses.

Purification and Analysis

  • The exosome preparations were further purified using FPLC gel filtration, a method used to separate and purify proteins according to their size.
  • Different filtration profiles were displayed by individual preparations, with some showing clear separation of exosome peaks and others not.
  • The study examined the samples using electron microscopy and found that well-purified exosomes exhibited the typical size and morphology expected of exosomes.
  • The study confirmed that exosomes can perform various biological functions, however, the detection of these functions can significantly vary based on the presence of exosome contaminating proteins and proteins directly into exosomes.

Protein Identification

  • The next phase of the research involved identifying the proteins present in the exosomes. This was done both before and after gel filtration using MALDI mass spectrometry and tandem mass spectrometry of protein tryptic hydrolyzates derived by SDS PAGE and 2D electrophoresis.
  • The results were unexpected, with one or two protein peaks isolating after gel-filtration mainly containing kappa-, beta-, alpha-S1-caseins and its precursors, however, these proteins were not discovered in well-purified exosomes.
  • Instead, five to eight different major proteins were found in the well-purified samples.

Conclusion

  • This is the first report detailing the morphology and protein content of major horse milk exosomes. The researchers pointed out that their results can play a significant role in future studies of the biological functions of pure exosomes, particularly due to the decrease of major protein number identified in exosomal preparations after gel filtration.

Cite This Article

APA
Sedykh SE, Purvinish LV, Monogarov AS, Burkova EE, Grigor'eva AE, Bulgakov DV, Dmitrenok PS, Vlassov VV, Ryabchikova EI, Nevinsky GA. (2017). Purified horse milk exosomes contain an unpredictable small number of major proteins. Biochim Open, 4, 61-72. https://doi.org/10.1016/j.biopen.2017.02.004

Publication

Biochimie open
ISSN: 2214-0085
NlmUniqueID: 101706117
Country: Netherlands
Language: English
Volume: 4
Pages: 61-72

Researcher Affiliations

Sedykh, Sergey E
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
  • Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
Purvinish, Lada V
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
  • Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
Monogarov, Artem S
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
Burkova, Evgeniya E
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
  • Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
Grigor'eva, Alina E
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
Bulgakov, Dmitrii V
  • Institute of Biology and Soil, Far East Division, Russian Academy of Sciences, Vladivostok 690022, Russia.
Dmitrenok, Pavel S
  • Pacific Institute of Bioorganic Chemistry, Far East Division, Russian Academy of Sciences, Vladivostok 690022, Russia.
Vlassov, Valentin V
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
  • Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
Ryabchikova, Elena I
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
  • Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
Nevinsky, Georgy A
  • SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
  • Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.

References

This article includes 51 references
  1. Melnik BC, John SM, Schmitz G. Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth.. Nutr J 2013 Jul 25;12:103.
    pmc: PMC3725179pubmed: 23883112doi: 10.1186/1475-2891-12-103google scholar: lookup
  2. Reinhardt TA, Lippolis JD, Nonnecke BJ, Sacco RE. Bovine milk exosome proteome.. J Proteomics 2012 Feb 16;75(5):1486-92.
    pubmed: 22129587doi: 10.1016/j.jprot.2011.11.017google scholar: lookup
  3. Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, Gho YS, Kurochkin IV, Mathivanan S, Quesenberry P, Sahoo S, Tahara H, Wauben MH, Witwer KW, Théry C. 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.
    pmc: PMC4275645pubmed: 25536934doi: 10.3402/jev.v3.26913google scholar: lookup
  4. Nakayama A. [Proteomic analysis of urinary exosomes].. Rinsho Byori 2014 Jul;62(7):684-91.
    pubmed: 25669038
  5. Raimondo F, Morosi L, Chinello C, Magni F, Pitto M. Advances in membranous vesicle and exosome proteomics improving biological understanding and biomarker discovery.. Proteomics 2011 Feb;11(4):709-20.
    pubmed: 21241021doi: 10.1002/pmic.201000422google scholar: lookup
  6. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials.. Biochim Biophys Acta 2012 Jul;1820(7):940-8.
    pubmed: 22503788doi: 10.1016/j.bbagen.2012.03.017google scholar: lookup
  7. Théry C. Exosomes: secreted vesicles and intercellular communications.. F1000 Biol Rep 2011;3:15.
    pmc: PMC3155154pubmed: 21876726doi: 10.3410/b3-15google scholar: lookup
  8. Turturici G, Tinnirello R, Sconzo G, Geraci F. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages.. Am J Physiol Cell Physiol 2014 Apr 1;306(7):C621-33.
    pubmed: 24452373doi: 10.1152/ajpcell.00228.2013google scholar: lookup
  9. Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication.. Curr Opin Cell Biol 2009 Aug;21(4):575-81.
    pubmed: 19442504doi: 10.1016/j.ceb.2009.03.007google scholar: lookup
  10. Aryani A, Denecke B. Exosomes as a Nanodelivery System: a Key to the Future of Neuromedicine?. Mol Neurobiol 2016 Mar;53(2):818-834.
    pmc: PMC4752585pubmed: 25502465doi: 10.1007/s12035-014-9054-5google scholar: lookup
  11. Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, Patel T, Piroyan A, Sokolsky M, Kabanov AV, Batrakova EV. Exosomes as drug delivery vehicles for Parkinson's disease therapy.. J Control Release 2015 Jun 10;207:18-30.
    pmc: PMC4430381pubmed: 25836593doi: 10.1016/j.jconrel.2015.03.033google scholar: lookup
  12. Admyre C, Johansson SM, Qazi KR, Filén JJ, Lahesmaa R, Norman M, Neve EP, Scheynius A, Gabrielsson S. Exosomes with immune modulatory features are present in human breast milk.. J Immunol 2007 Aug 1;179(3):1969-78.
    pubmed: 17641064doi: 10.4049/jimmunol.179.3.1969google scholar: lookup
  13. Liao Y, Alvarado R, Phinney B, Lönnerdal B. Proteomic characterization of human milk whey proteins during a twelve-month lactation period.. J Proteome Res 2011 Apr 1;10(4):1746-54.
    pubmed: 21361340doi: 10.1021/pr101028kgoogle scholar: lookup
  14. Zonneveld MI, Brisson AR, van Herwijnen MJ, Tan S, van de Lest CH, Redegeld FA, Garssen J, Wauben MH, Nolte-'t Hoen EN. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures.. J Extracell Vesicles 2014;3.
    pmc: PMC4139932pubmed: 25206958doi: 10.3402/jev.v3.24215google scholar: lookup
  15. Lässer C, Alikhani VS, Ekström K, Eldh M, Paredes PT, Bossios A, Sjöstrand M, Gabrielsson S, Lötvall J, Valadi H. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages.. J Transl Med 2011 Jan 14;9:9.
    pmc: PMC3033821pubmed: 21235781doi: 10.1186/1479-5876-9-9google scholar: lookup
  16. Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, Zhou X, Wang X, Gao X, Li X. Immune-related microRNAs are abundant in breast milk exosomes.. Int J Biol Sci 2012;8(1):118-23.
    pmc: PMC3248653pubmed: 22211110doi: 10.7150/ijbs.8.118google scholar: lookup
  17. Torregrosa Paredes P, Gutzeit C, Johansson S, Admyre C, Stenius F, Alm J, Scheynius A, Gabrielsson S. Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle.. Allergy 2014 Apr;69(4):463-71.
    pubmed: 24428462doi: 10.1111/all.12357google scholar: lookup
  18. Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery.. Cancer Lett 2016 Feb 1;371(1):48-61.
    pmc: PMC4706492pubmed: 26604130doi: 10.1016/j.canlet.2015.10.020google scholar: lookup
  19. Yamada T, Inoshima Y, Matsuda T, Ishiguro N. Comparison of methods for isolating exosomes from bovine milk.. J Vet Med Sci 2012 Nov;74(11):1523-5.
    pubmed: 22785357doi: 10.1292/jvms.12-0032google scholar: lookup
  20. Gu Y, Li M, Wang T, Liang Y, Zhong Z, Wang X, Zhou Q, Chen L, Lang Q, He Z, Chen X, Gong J, Gao X, Li X, Lv X. Lactation-related microRNA expression profiles of porcine breast milk exosomes.. PLoS One 2012;7(8):e43691.
    pmc: PMC3427246pubmed: 22937080doi: 10.1371/journal.pone.0043691google scholar: lookup
  21. Ferguson SW, Nguyen J. Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity.. J Control Release 2016 Apr 28;228:179-190.
    pubmed: 26941033doi: 10.1016/j.jconrel.2016.02.037google scholar: lookup
  22. Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang HG. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.. Mol Ther 2010 Sep;18(9):1606-14.
    pmc: PMC2956928pubmed: 20571541doi: 10.1038/mt.2010.105google scholar: lookup
  23. Rout ED, Webb TL, Laurence HM, Long L, Olver CS. Transferrin receptor expression in serum exosomes as a marker of regenerative anaemia in the horse.. Equine Vet J 2015 Jan;47(1):101-6.
    pubmed: 24708277doi: 10.1111/evj.12235google scholar: lookup
  24. Thery C., Amigorena S., Raposo G., Clayton A. In: Current Protocols in Cell Biology. Chambers C., editor. John Wiley & Sons, Ltd.; 2006. (Chapter 3, Unit 3.22)
  25. Ji H, Erfani N, Tauro BJ, Kapp EA, Zhu HJ, Moritz RL, Lim JW, Simpson RJ. Difference gel electrophoresis analysis of Ras-transformed fibroblast cell-derived exosomes.. Electrophoresis 2008 Jun;29(12):2660-71.
    pubmed: 18494037doi: 10.1002/elps.200800015google scholar: lookup
  26. Cvjetkovic A, Lötvall J, Lässer C. The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles.. J Extracell Vesicles 2014;3.
    pmc: PMC3967015pubmed: 24678386doi: 10.3402/jev.v3.23111google scholar: lookup
  27. Lamparski HG, Metha-Damani A, Yao JY, Patel S, Hsu DH, Ruegg C, Le Pecq JB. Production and characterization of clinical grade exosomes derived from dendritic cells.. J Immunol Methods 2002 Dec 15;270(2):211-26.
    pubmed: 12379326doi: 10.1016/s0022-1759(02)00330-7google scholar: lookup
  28. Brownlee Z, Lynn KD, Thorpe PE, Schroit AJ. A novel "salting-out" procedure for the isolation of tumor-derived exosomes.. J Immunol Methods 2014 May;407:120-6.
    pmc: PMC4077054pubmed: 24735771doi: 10.1016/j.jim.2014.04.003google scholar: lookup
  29. Gatti JL, Métayer S, Belghazi M, Dacheux F, Dacheux JL. Identification, proteomic profiling, and origin of ram epididymal fluid exosome-like vesicles.. Biol Reprod 2005 Jun;72(6):1452-65.
    pubmed: 15635128doi: 10.1095/biolreprod.104.036426google scholar: lookup
  30. Théry C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.. J Cell Biol 1999 Nov 1;147(3):599-610.
    pmc: PMC2151184pubmed: 10545503doi: 10.1083/jcb.147.3.599google scholar: lookup
  31. Théry C, Boussac M, Véron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Amigorena S. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles.. J Immunol 2001 Jun 15;166(12):7309-18.
    pubmed: 11390481doi: 10.4049/jimmunol.166.12.7309google scholar: lookup
  32. Segura E, Nicco C, Lombard B, Véron P, Raposo G, Batteux F, Amigorena S, Théry C. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming.. Blood 2005 Jul 1;106(1):216-23.
    pubmed: 15790784doi: 10.1182/blood-2005-01-0220google scholar: lookup
  33. Morelli AE, Larregina AT, Shufesky WJ, Sullivan ML, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD Jr, Thomson AW. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.. Blood 2004 Nov 15;104(10):3257-66.
    pubmed: 15284116doi: 10.1182/blood-2004-03-0824google scholar: lookup
  34. Lozano-Ramos I, Bancu I, Oliveira-Tercero A, Armengol MP, Menezes-Neto A, Del Portillo HA, Lauzurica-Valdemoros R, Borràs FE. Size-exclusion chromatography-based enrichment of extracellular vesicles from urine samples.. J Extracell Vesicles 2015;4:27369.
    pmc: PMC4449362pubmed: 26025625doi: 10.3402/jev.v4.27369google scholar: lookup
  35. Welton JL, Webber JP, Botos LA, Jones M, Clayton A. Ready-made chromatography columns for extracellular vesicle isolation from plasma.. J Extracell Vesicles 2015;4:27269.
    pmc: PMC4376847pubmed: 25819214doi: 10.3402/jev.v4.27269google scholar: lookup
  36. Soboleva SE, Dmitrenok PS, Verkhovod TD, Buneva VN, Sedykh SE, Nevinsky GA. Very stable high molecular mass multiprotein complex with DNase and amylase activities in human milk.. J Mol Recognit 2015 Jan;28(1):20-34.
    pubmed: 26268368doi: 10.1002/jmr.2409google scholar: lookup
  37. Burkova EE, Dmitrenok PS, Sedykh SE, Buneva VN, Soboleva SE, Nevinsky GA. Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.. PLoS One 2014;9(11):e111234.
    pmc: PMC4245193pubmed: 25426722doi: 10.1371/journal.pone.0111234google scholar: lookup
  38. Hong CS, Muller L, Whiteside TL, Boyiadzis M. Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia.. Front Immunol 2014;5:160.
    pmc: PMC3989594pubmed: 24782865doi: 10.3389/fimmu.2014.00160google scholar: lookup
  39. Torregrosa Paredes P, Gutzeit C, Johansson S, Admyre C, Stenius F, Alm J, Scheynius A, Gabrielsson S. Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle.. Allergy 2014 Apr;69(4):463-71.
    pubmed: 24428462doi: 10.1111/all.12357google scholar: lookup
  40. Kontopidis G, Holt C, Sawyer L. Invited review: beta-lactoglobulin: binding properties, structure, and function.. J Dairy Sci 2004 Apr;87(4):785-96.
    pubmed: 15259212doi: 10.3168/jds.s0022-0302(04)73222-1google scholar: lookup
  41. Larsson A, Peng S, Persson H, Rosenbloom J, Abrams WR, Wassberg E, Thelin S, Sletten K, Gerwins P, Westermark P. Lactadherin binds to elastin--a starting point for medin amyloid formation?. Amyloid 2006 Jun;13(2):78-85.
    pubmed: 16911961doi: 10.1080/13506120600722530google scholar: lookup
  42. Peng S, Glennert J, Westermark P. Medin-amyloid: a recently characterized age-associated arterial amyloid form affects mainly arteries in the upper part of the body.. Amyloid 2005 Jun;12(2):96-102.
    pubmed: 16011985doi: 10.1080/13506120500107006google scholar: lookup
  43. Silvestre JS, Théry C, Hamard G, Boddaert J, Aguilar B, Delcayre A, Houbron C, Tamarat R, Blanc-Brude O, Heeneman S, Clergue M, Duriez M, Merval R, Lévy B, Tedgui A, Amigorena S, Mallat Z. Lactadherin promotes VEGF-dependent neovascularization.. Nat Med 2005 May;11(5):499-506.
    pubmed: 15834428doi: 10.1038/nm1233google scholar: lookup
  44. Doherty GJ, McMahon HT. Mediation, modulation, and consequences of membrane-cytoskeleton interactions.. Annu Rev Biophys 2008;37:65-95.
    pubmed: 18573073doi: 10.1146/annurev.biophys.37.032807.125912google scholar: lookup
  45. Ogg SL, Weldon AK, Dobbie L, Smith AJ, Mather IH. Expression of butyrophilin (Btn1a1) in lactating mammary gland is essential for the regulated secretion of milk-lipid droplets.. Proc Natl Acad Sci U S A 2004 Jul 6;101(27):10084-9.
    pmc: PMC454168pubmed: 15226505doi: 10.1073/pnas.0402930101google scholar: lookup
  46. Albar AH, Almehdar HA, Uversky VN, Redwan EM. Structural heterogeneity and multifunctionality of lactoferrin.. Curr Protein Pept Sci 2014;15(8):778-97.
    pubmed: 25245670doi: 10.2174/1389203715666140919124530google scholar: lookup
  47. Stipek S, Novak L, Crkovska J, Zima T, Platenik J. Xanthine oxidoreductase. Biochemical, biological and pathogenic functions.. Sb Lek 1994;95(4):289-95.
    pubmed: 8867700
  48. Chmurzyńska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism.. J Appl Genet 2006;47(1):39-48.
    pubmed: 16424607doi: 10.1007/bf03194597google scholar: lookup
  49. Weisiger RA. Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands.. Mol Cell Biochem 2002 Oct;239(1-2):35-43.
    pubmed: 12479566
  50. Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N. Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription.. Mol Cell Biol 2002 Jul;22(14):5114-27.
    pmc: PMC139777pubmed: 12077340doi: 10.1128/mcb.22.14.5114-5127.2002google scholar: lookup
  51. Pu L, Igbavboa U, Wood WG, Roths JB, Kier AB, Spener F, Schroeder F. Expression of fatty acid binding proteins is altered in aged mouse brain.. Mol Cell Biochem 1999 Aug;198(1-2):69-78.
    pubmed: 10497880doi: 10.1023/a:1006946027619google scholar: lookup

Citations

This article has been cited 36 times.
  1. Tupitsyna AV, Grigorieva AE, Soboleva SE, Maltseva NA, Sedykh SE, Poletaeva J, Dmitrenok PS, Ryabchikova EI, Nevinsky GA. Isolation of Extracellular Vesicles of Holothuria (Sea Cucumber Eupentacta fraudatrix). Int J Mol Sci 2023 Aug 17;24(16).
    doi: 10.3390/ijms241612907pubmed: 37629088google scholar: lookup
  2. Buratta S, Urbanelli L, Tognoloni A, Latella R, Cerrotti G, Emiliani C, Chiaradia E. Protein and Lipid Content of Milk Extracellular Vesicles: A Comparative Overview. Life (Basel) 2023 Feb 1;13(2).
    doi: 10.3390/life13020401pubmed: 36836757google scholar: lookup
  3. Sedykh SE, Purvinsh LV, Burkova EE, Dmitrenok PS, Ryabchikova EI, Nevinsky GA. Analysis of Proteins and Peptides of Highly Purified CD9(+) and CD63(+) Horse Milk Exosomes Isolated by Affinity Chromatography. Int J Mol Sci 2022 Dec 17;23(24).
    doi: 10.3390/ijms232416106pubmed: 36555744google scholar: lookup
  4. Mecocci S, Trabalza-Marinucci M, Cappelli K. Extracellular Vesicles from Animal Milk: Great Potentialities and Critical Issues. Animals (Basel) 2022 Nov 22;12(23).
    doi: 10.3390/ani12233231pubmed: 36496752google scholar: lookup
  5. Rashidi M, Bijari S, Khazaei AH, Shojaei-Ghahrizjani F, Rezakhani L. The role of milk-derived exosomes in the treatment of diseases. Front Genet 2022;13:1009338.
    doi: 10.3389/fgene.2022.1009338pubmed: 36338966google scholar: lookup
  6. Li X, Su L, Zhang X, Chen Q, Wang Y, Shen Z, Zhong T, Wang L, Xiao Y, Feng X, Yu X. Recent Advances on the Function and Purification of Milk Exosomes: A Review. Front Nutr 2022;9:871346.
    doi: 10.3389/fnut.2022.871346pubmed: 35757254google scholar: lookup
  7. Babaker MA, Aljoud FA, Alkhilaiwi F, Algarni A, Ahmed A, Khan MI, Saadeldin IM, Alzahrani FA. The Therapeutic Potential of Milk Extracellular Vesicles on Colorectal Cancer. Int J Mol Sci 2022 Jun 18;23(12).
    doi: 10.3390/ijms23126812pubmed: 35743255google scholar: lookup
  8. Mecocci S, Pietrucci D, Milanesi M, Pascucci L, Filippi S, Rosato V, Chillemi G, Capomaccio S, Cappelli K. Transcriptomic Characterization of Cow, Donkey and Goat Milk Extracellular Vesicles Reveals Their Anti-Inflammatory and Immunomodulatory Potential. Int J Mol Sci 2021 Nov 25;22(23).
    doi: 10.3390/ijms222312759pubmed: 34884564google scholar: lookup
  9. Hu Y, Thaler J, Nieuwland R. Extracellular Vesicles in Human Milk. Pharmaceuticals (Basel) 2021 Oct 15;14(10).
    doi: 10.3390/ph14101050pubmed: 34681274google scholar: lookup
  10. Ong SL, Blenkiron C, Haines S, Acevedo-Fani A, Leite JAS, Zempleni J, Anderson RC, McCann MJ. Ruminant Milk-Derived Extracellular Vesicles: A Nutritional and Therapeutic Opportunity?. Nutrients 2021 Jul 22;13(8).
    doi: 10.3390/nገ2505pubmed: 34444665google scholar: lookup
  11. Sanwlani R, Fonseka P, Mathivanan S. Are Dietary Extracellular Vesicles Bioavailable and Functional in Consuming Organisms?. Subcell Biochem 2021;97:509-521.
    doi: 10.1007/978-3-030-67171-6_21pubmed: 33779931google scholar: lookup
  12. Burkova EE, Sedykh SE, Nevinsky GA. Human Placenta Exosomes: Biogenesis, Isolation, Composition, and Prospects for Use in Diagnostics. Int J Mol Sci 2021 Feb 22;22(4).
    doi: 10.3390/ijms22042158pubmed: 33671527google scholar: lookup
  13. Adriano B, Cotto NM, Chauhan N, Jaggi M, Chauhan SC, Yallapu MM. Milk exosomes: Nature's abundant nanoplatform for theranostic applications. Bioact Mater 2021 Aug;6(8):2479-2490.
    doi: 10.1016/j.bioactmat.2021.01.009pubmed: 33553829google scholar: lookup
  14. Bollard SM, Casalou C, Goh CY, Tobin DJ, Kelly P, McCann A, Potter SM. Circulating Melanoma-Derived Extracellular Vesicles: Impact on Melanoma Diagnosis, Progression Monitoring, and Treatment Response. Pharmaceuticals (Basel) 2020 Dec 18;13(12).
    doi: 10.3390/ph13120475pubmed: 33353043google scholar: lookup
  15. Villatoro AJ, Martín-Astorga MDC, Alcoholado C, Becerra J. Canine colostrum exosomes: characterization and influence on the canine mesenchymal stem cell secretory profile and fibroblast anti-oxidative capacity. BMC Vet Res 2020 Nov 2;16(1):417.
    doi: 10.1186/s12917-020-02623-wpubmed: 33138803google scholar: lookup
  16. Sedykh S, Kuleshova A, Nevinsky G. Milk Exosomes: Perspective Agents for Anticancer Drug Delivery. Int J Mol Sci 2020 Sep 11;21(18).
    doi: 10.3390/ijms21186646pubmed: 32932782google scholar: lookup
  17. Sanwlani R, Fonseka P, Chitti SV, Mathivanan S. Milk-Derived Extracellular Vesicles in Inter-Organism, Cross-Species Communication and Drug Delivery. Proteomes 2020 May 13;8(2).
    doi: 10.3390/proteomes8020011pubmed: 32414045google scholar: lookup
  18. Ledda B, Ottaggio L, Izzotti A, Sukkar SG, Miele M. Small RNAs in eucaryotes: new clues for amplifying microRNA benefits. Cell Biosci 2020;10:1.
    doi: 10.1186/s13578-019-0370-3pubmed: 31911829google scholar: lookup
  19. Munir J, Lee M, Ryu S. Exosomes in Food: Health Benefits and Clinical Relevance in Diseases. Adv Nutr 2020 May 1;11(3):687-696.
    doi: 10.1093/advances/nmz123pubmed: 31796948google scholar: lookup
  20. Burkova EE, Grigor'eva AE, Bulgakov DV, Dmitrenok PS, Vlassov VV, Ryabchikova EI, Sedykh SE, Nevinsky GA. Extra Purified Exosomes from Human Placenta Contain An Unpredictable Small Number of Different Major Proteins. Int J Mol Sci 2019 May 16;20(10).
    doi: 10.3390/ijms20102434pubmed: 31100946google scholar: lookup
  21. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, Ayre DC, Bach JM, Bachurski D, Baharvand H, Balaj L, Baldacchino S, Bauer NN, Baxter AA, Bebawy M, Beckham C, Bedina Zavec A, Benmoussa A, Berardi AC, Bergese P, Bielska E, Blenkiron C, Bobis-Wozowicz S, Boilard E, Boireau W, Bongiovanni A, Borràs FE, Bosch S, Boulanger CM, Breakefield X, Breglio AM, Brennan MÁ, Brigstock DR, Brisson A, Broekman ML, Bromberg JF, Bryl-Górecka P, Buch S, Buck AH, Burger D, Busatto S, Buschmann D, Bussolati B, Buzás EI, Byrd JB, Camussi G, Carter DR, Caruso S, Chamley LW, Chang YT, Chen C, Chen S, Cheng L, Chin AR, Clayton A, Clerici SP, Cocks A, Cocucci E, Coffey RJ, Cordeiro-da-Silva A, Couch Y, Coumans FA, Coyle B, Crescitelli R, Criado MF, D'Souza-Schorey C, Das S, Datta Chaudhuri A, de Candia P, De Santana EF, De Wever O, Del Portillo HA, Demaret T, Deville S, Devitt A, Dhondt B, Di Vizio D, Dieterich LC, Dolo V, Dominguez Rubio AP, Dominici M, Dourado MR, Driedonks TA, Duarte FV, Duncan HM, Eichenberger RM, Ekström K, El Andaloussi S, Elie-Caille C, Erdbrügger U, Falcón-Pérez JM, Fatima F, Fish JE, Flores-Bellver M, Försönits A, Frelet-Barrand A, Fricke F, Fuhrmann G, Gabrielsson S, Gámez-Valero A, Gardiner C, Gärtner K, Gaudin R, Gho YS, Giebel B, Gilbert C, Gimona M, Giusti I, Goberdhan DC, Görgens A, Gorski SM, Greening DW, Gross JC, Gualerzi A, Gupta GN, Gustafson D, Handberg A, Haraszti RA, Harrison P, Hegyesi H, Hendrix A, Hill AF, Hochberg FH, Hoffmann KF, Holder B, Holthofer H, Hosseinkhani B, Hu G, Huang Y, Huber V, Hunt S, Ibrahim AG, Ikezu T, Inal JM, Isin M, Ivanova A, Jackson HK, Jacobsen S, Jay SM, Jayachandran M, Jenster G, Jiang L, Johnson SM, Jones JC, Jong A, Jovanovic-Talisman T, Jung S, Kalluri R, Kano SI, Kaur S, Kawamura Y, Keller ET, Khamari D, Khomyakova E, Khvorova A, Kierulf P, Kim KP, Kislinger T, Klingeborn M, Klinke DJ 2nd, Kornek M, Kosanović MM, Kovács ÁF, Krämer-Albers EM, Krasemann S, Krause M, Kurochkin IV, Kusuma GD, Kuypers S, Laitinen S, Langevin SM, Languino LR, Lannigan J, Lässer C, Laurent LC, Lavieu G, Lázaro-Ibáñez E, Le Lay S, Lee MS, Lee YXF, Lemos DS, Lenassi M, Leszczynska A, Li IT, Liao K, Libregts SF, Ligeti E, Lim R, Lim SK, Linē A, Linnemannstöns K, Llorente A, Lombard CA, Lorenowicz MJ, Lörincz ÁM, Lötvall J, Lovett J, Lowry MC, Loyer X, Lu Q, Lukomska B, Lunavat TR, Maas SL, Malhi H, Marcilla A, Mariani J, Mariscal J, Martens-Uzunova ES, Martin-Jaular L, Martinez MC, Martins VR, Mathieu M, Mathivanan S, Maugeri M, McGinnis LK, McVey MJ, Meckes DG Jr, Meehan KL, Mertens I, Minciacchi VR, Möller A, Møller Jørgensen M, Morales-Kastresana A, Morhayim J, Mullier F, Muraca M, Musante L, Mussack V, Muth DC, Myburgh KH, Najrana T, Nawaz M, Nazarenko I, Nejsum P, Neri C, Neri T, Nieuwland R, Nimrichter L, Nolan JP, Nolte-'t Hoen EN, Noren Hooten N, O'Driscoll L, O'Grady T, O'Loghlen A, Ochiya T, Olivier M, Ortiz A, Ortiz LA, Osteikoetxea X, Østergaard O, Ostrowski M, Park J, Pegtel DM, Peinado H, Perut F, Pfaffl MW, Phinney DG, Pieters BC, Pink RC, Pisetsky DS, Pogge von Strandmann E, Polakovicova I, Poon IK, Powell BH, Prada I, Pulliam L, Quesenberry P, Radeghieri A, Raffai RL, Raimondo S, Rak J, Ramirez MI, Raposo G, Rayyan MS, Regev-Rudzki N, Ricklefs FL, Robbins PD, Roberts DD, Rodrigues SC, Rohde E, Rome S, Rouschop KM, Rughetti A, Russell AE, Saá P, Sahoo S, Salas-Huenuleo E, Sánchez C, Saugstad JA, Saul MJ, Schiffelers RM, Schneider R, Schøyen TH, Scott A, Shahaj E, Sharma S, Shatnyeva O, Shekari F, Shelke GV, Shetty AK, Shiba K, Siljander PR, Silva AM, Skowronek A, Snyder OL 2nd, Soares RP, Sódar BW, Soekmadji C, Sotillo J, Stahl PD, Stoorvogel W, Stott SL, Strasser EF, Swift S, Tahara H, Tewari M, Timms K, Tiwari S, Tixeira R, Tkach M, Toh WS, Tomasini R, Torrecilhas AC, Tosar JP, Toxavidis V, Urbanelli L, Vader P, van Balkom BW, van der Grein SG, Van Deun J, van Herwijnen MJ, Van Keuren-Jensen K, van Niel G, van Royen ME, van Wijnen AJ, Vasconcelos MH, Vechetti IJ Jr, Veit TD, Vella LJ, Velot É, Verweij FJ, Vestad B, Viñas JL, Visnovitz T, Vukman KV, Wahlgren J, Watson DC, Wauben MH, Weaver A, Webber JP, Weber V, Wehman AM, Weiss DJ, Welsh JA, Wendt S, Wheelock AM, Wiener Z, Witte L, Wolfram J, Xagorari A, Xander P, Xu J, Yan X, Yáñez-Mó M, Yin H, Yuana Y, Zappulli V, Zarubova J, Žėkas V, Zhang JY, Zhao Z, Zheng L, Zheutlin AR, Zickler AM, Zimmermann P, Zivkovic AM, Zocco D, Zuba-Surma EK. 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.
    doi: 10.1080/20013078.2018.1535750pubmed: 30637094google scholar: lookup
  22. van Herwijnen MJC, Driedonks TAP, Snoek BL, Kroon AMT, Kleinjan M, Jorritsma R, Pieterse CMJ, Hoen ENMN, Wauben MHM. Abundantly Present miRNAs in Milk-Derived Extracellular Vesicles Are Conserved Between Mammals. Front Nutr 2018;5:81.
    doi: 10.3389/fnut.2018.00081pubmed: 30280098google scholar: lookup
  23. Hussain S, Ijaz S, Wajid A, Qadeer A, Suliman M, Alzahrani FM, Alzahrani KJ, Alsharif KF, Chang CW, Chen CC. Decoding the functional plasticity of milk-derived exosomes: implications for nutrition, immunity, and therapy. Front Immunol 2025;16:1645355.
    doi: 10.3389/fimmu.2025.1645355pubmed: 41164184google scholar: lookup
  24. Soltanmohammadi F, Maghsoodi M, Alizadeh E, Adibkia K, Azarmi Y, Mahmoudi Gharehbaba A, Javadzadeh Y. Bio fluid exosomes: promises, challenges, and future directions in translational medicine. J Transl Med 2025 Sep 23;23(1):993.
    doi: 10.1186/s12967-025-06886-5pubmed: 40988065google scholar: lookup
  25. Santoro J, Nuzzo S, Soricelli A, Salvatore M, Grimaldi AM. RNAi delivery mediated by milk extracellular vesicles in colon cancer. Mol Ther Nucleic Acids 2025 Sep 9;36(3):102644.
    doi: 10.1016/j.omtn.2025.102644pubmed: 40896585google scholar: lookup
  26. Kong C, Huang LB, Yang MF, Yue NN, Zhang Y, Tian CM, Wang YH, Wei DR, Shi RY, Liang YJ, Yao J, Wang LS, Li DF. Milk-derived extracellular vesicles: nature's nanocarriers for drug delivery and therapeutics. Front Pharmacol 2025;16:1595891.
    doi: 10.3389/fphar.2025.1595891pubmed: 40843370google scholar: lookup
  27. Chen X, Gulbahar K, Ding H, Nie C, Gao X. Comparative analysis of proteomics and transcriptomics reveals novel mechanism underlying the antibacterial activity and immune-enhancing properties of horse milk. Front Nutr 2025;12:1512669.
    doi: 10.3389/fnut.2025.1512669pubmed: 40135224google scholar: lookup
  28. Muttiah B, Law JX. Milk-derived extracellular vesicles and gut health. NPJ Sci Food 2025 Jan 30;9(1):12.
    doi: 10.1038/s41538-025-00375-1pubmed: 39885215google scholar: lookup
  29. Sergazy S, Seydahmetova R, Gulyayev A, Shulgau Z, Aljofan M. The Role of Exosomes in Cancer Progression and Therapy. Biology (Basel) 2025 Jan 1;14(1).
    doi: 10.3390/biology14010027pubmed: 39857258google scholar: lookup
  30. Poletaeva JE, Tupitsyna AV, Grigor'eva AE, Dovydenko IS, Ryabchikova EI. Attempts to preserve and visualize protein corona on the surface of biological nanoparticles in blood serum using photomodification. Beilstein J Nanotechnol 2024;15:1654-1666.
    doi: 10.3762/bjnano.15.130pubmed: 39764069google scholar: lookup
  31. Bollard SM, Howard J, Casalou C, Kelly BS, O'Donnell K, Fenn G, O'Reilly J, Milling R, Shields M, Wilson M, Ajaykumar A, Triana K, Wynne K, Tobin DJ, Kelly PA, McCann A, Potter SM. Proteomic and metabolomic profiles of plasma-derived Extracellular Vesicles differentiate melanoma patients from healthy controls. Transl Oncol 2024 Dec;50:102152.
    doi: 10.1016/j.tranon.2024.102152pubmed: 39405606google scholar: lookup
  32. Mecocci S, Pietrucci D, Milanesi M, Capomaccio S, Pascucci L, Evangelista C, Basiricò L, Bernabucci U, Chillemi G, Cappelli K. Comparison of colostrum and milk extracellular vesicles small RNA cargo in water buffalo. Sci Rep 2024 Aug 3;14(1):17991.
    doi: 10.1038/s41598-024-67249-6pubmed: 39097641google scholar: lookup
  33. Aare M, Bagde A, Nathani A, Rishi AK, Singh M. Enhanced oral bioavailability and in vitro evaluation of cannabidiol camel milk-derived exosome formulation in resistant MDA-MB-231 and MDA-MB-468 breast cancer cells. Int J Pharm 2024 Sep 30;663:124375.
    doi: 10.1016/j.ijpharm.2024.124375pubmed: 38914353google scholar: lookup
  34. Aresta AM, De Vietro N, Zambonin C. Analysis and Characterization of the Extracellular Vesicles Released in Non-Cancer Diseases Using Matrix-Assisted Laser Desorption Ionization/Mass Spectrometry. Int J Mol Sci 2024 Apr 19;25(8).
    doi: 10.3390/ijms25084490pubmed: 38674075google scholar: lookup
  35. Samuel M, Sanwlani R, Pathan M, Anand S, Johnston EL, Ang CS, Kaparakis-Liaskos M, Mathivanan S. Isolation and Characterization of Cow-, Buffalo-, Sheep- and Goat-Milk-Derived Extracellular Vesicles. Cells 2023 Oct 20;12(20).
    doi: 10.3390/cells12202491pubmed: 37887335google scholar: lookup
  36. Timofeeva AM, Paramonik AP, Sedykh SS, Nevinsky GA. Milk Exosomes: Next-Generation Agents for Delivery of Anticancer Drugs and Therapeutic Nucleic Acids. Int J Mol Sci 2023 Jun 15;24(12).
    doi: 10.3390/ijms241210194pubmed: 37373342google scholar: lookup
Subscribe to our newsletter
Join 99,359 horse owners like you who receive our email updates on horse health and nutrition.