Skip to main content
SpringerLink
Log in

Extracellular Vesicles of Pluripotent Stem Cells

  • 80 YEARS OF THE DEPARTMENT OF EMBRYOLOGY, MOSCOW STATE UNIVERSITY
  • Published:
Russian Journal of Developmental Biology Aims and scope Submit manuscript

Abstract

The review article presents data on extracellular vesicles (EV), bilayer phospholipid membrane structures which are secreted by different cell types and contain proteins, lipids, and nucleic acids. The features of their structure, biogenesis, and mechanisms of interaction with the recipient cell are considered. The properties of extracellular vesicles of embryonic stem cells (ESCs) and their role in the regulation of developmental processes are also considered. Special attention is paid to the vesicles of induced pluripotent stem cells (iPSCs), their role in maintaining pluripotency, and the properties of the vesicles of cells obtained during the directed differentiation of iPSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Adamiak, M., Cheng, G., Bobis-Wozowicz, S., et al., Induced pluripotent stem cell (iPSC)-derived extracellular vesicles are safer and more effective for cardiac repair than iPSCs, Circ. Res., 2018, vol. 122, no. 2, pp. 296–309.

  2. Airola, M. and Hannun, Y., Sphingolipid metabolism and neutral sphingomyelinases, Handb. Exp. Pharmacol., 2013, vol. 215, pp. 57–76.

    Article  CAS  Google Scholar 

  3. Alcayaga-Miranda, F., Varas-Goboy, M., and Khoury, M., Harnessing the angiogenic potential of stem cell-derived exosomes for vascular regeneration, Stem Cells Int., 2016.

  4. Anderson, H., Vesicles associated with calcification in the matrix of epiphyseal cartilage, J. Cell Biol., 1969, vol. 41, no. 1, pp. 59–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Battaglia, R., Palini, S., Vento, M., et al., Identification of extracellular vesicles and characterization of mirna expression profiles in human blastocoel fluid, Sci. Rep., 2019, vol. 9, p. 84. https://doi.org/10.1038/s41598-018-36452-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Braam, S., Zeinstra, L., Litjens, S., et al., Recombinant vitronectin is a functionally defined substrate that supports human embryonic stem cell self-renewal via alphavbeta5 integrin, Stem Cells, 2008, vol. 26, no. 9, pp. 2257–2265.

    Article  CAS  PubMed  Google Scholar 

  7. Brons, I., Smithers, L., Trotter, M., et al., Derivation of pluripotent epiblast stem cells from mammalian embryos, Nature, 2007, vol. 12, no. 448 (7150), pp. 191–195.

    Article  CAS  Google Scholar 

  8. Capalbo, A., Ubaldi, F.-M., Cimadomo, D., et al., MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment, Fertil. Steril., 2016, vol. 105, pp. 225–235.

    Article  CAS  PubMed  Google Scholar 

  9. Chen, Y. and Lai, D., Pluripotent states of human embryonic stem cells, Cell Reprogram., 2015, vol. 17, no. 1, pp. 1–6. https://doi.org/10.1089/cell.2014.0061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen, B., Sun, Y., Zhang, J., et al., Human embryonic stem cell-derived exosomes promote pressure ulcer healing in aged mice by rejuvenating senescent endothelial cells, Stem Cell Res. Ther., 2019, vol. 10, p. 142. https://doi.org/10.1186/s13287-019-1253-6

    Article  PubMed  PubMed Central  Google Scholar 

  11. Colombo, M., Moita, C., Niel, G., et al., Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles, J. Cell Sci., 2013, vol. 126, no. 24, pp. 5553–5565.

    CAS  PubMed  Google Scholar 

  12. Cordes, K., Sheehy, N., White, M., et al., miR-145 and miR-143 regulate smooth muscle cell fate and plasticity, Nature, 2009, vol. 460, pp. 705–710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Coumans, F., Brisson, A., and Buzas, E., Methodological guidelines to study extracellular vesicles, Circ. Res., 2017, vol. 120, no. 10, pp. 1632–1648.

    Article  CAS  PubMed  Google Scholar 

  14. Cufaro, M., Pieragostino, D., Lanuti, P., et al., Extracellular vesicles and their potential use in monitoring cancer progression and therapy: the contribution of proteomics, J. Oncol., 2019, p. 1639854. https://doi.org/10.1155/2019/1639854

  15. Dalton, A., Microvesicles and vesicles of multivesicular bodies versus “virus-like” particles, J. Natl. Cancer Inst., 1975, vol. 54, no. 5, pp. 1137–1148.

    Article  CAS  PubMed  Google Scholar 

  16. Desrochers, L., Bordeleau, F., Reinhart-King, C., et al., Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation, Nat. Commun., 2016, vol. 7, p. 11958. https://doi.org/10.1038/ncomms11958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ding, Q., Sun, R., Wang, P., et al., Protective effects of human induced pluripotent stem cell-derived exosomes on high glucose-induced injury in human endothelial cells, Exp. Ther. Med., 2018, vol. 15, p. 4791.

    PubMed  PubMed Central  Google Scholar 

  18. Dodsworth, B., Hatje, K., Rostovskaya, M., et al., Profling of naive and primed human pluripotent stem cells reveals state-associated miRNAs, Sci. Rep., 2020, vol. 10, p. 10542. https://doi.org/10.1038/s41598-020-67376-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Espey, L. and Stutts, R., Exchange of cytoplasm between cells of the membrana granulosa in rabbit ovarian follicles, Biol. Reprod., 1972, vol. 6, no. 1, pp. 168–175.

    Article  CAS  PubMed  Google Scholar 

  20. Farber, D. and Katsman, D., Embryonic stem cell-derived microvesicles: could they be used for retinal regeneration?, Adv. Exp. Med. Biol., 2016, vol. 854, pp. 563–569.

    Article  CAS  PubMed  Google Scholar 

  21. Greening, D., Nguyen, H., Elgass, K., et al., Human endometrial exosomes contain hormone-specific cargo modulating trophoblast adhesive capacity: insights into endometrial–embryo interactions, Biol. Reprod., 2016, vol. 94, p. 38.

    Article  PubMed  CAS  Google Scholar 

  22. Gruber, A., Grandy, W., Balwierz, P., et al., Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways, Nucleic Acids Res., 2014, vol. 42, pp. 9313–9326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Guescini, M., Genedani, S., Stocchi, V., et al., Astrocytes and glioblastoma cells release exosomes carrying mtDNA, J. Neural Transm., 2010, vol. 117, pp. 1–4.

    Article  CAS  PubMed  Google Scholar 

  24. Gyorgy, B., Szabo, T., Paszoti, M., et al., Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles, Cell. Mol. Life Sci., 2011, vol. 68, no. 16, pp. 2667–2688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hanna, J., Cheng, A.W., Saha, K., et al., Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs, Proc. Natl. Acad. Sci. U. S. A., 2010, vol. 107, pp. 9222–9227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hayashi, Y., Furue, M., Okamoto, T., et al., Integrins regulate mouse embryonic stem cell self-renewal, Stem Cells, 2007, vol. 25, no. 12, pp. 3005–3015.

    Article  CAS  PubMed  Google Scholar 

  27. Henne, W., Buchkovich, N., and Emr, S., The ESCRT pathway, Dev. Cell, 2011, vol. 21, no. 1, pp. 77–91.

    Article  CAS  PubMed  Google Scholar 

  28. Ho, B., Olson, G., Figel, S., et al., Nanog increases focal adhesion kinase (FAK) promoter activity and expression and directly binds to FAK protein to be phosphorylated, J. Biol. Chem., 2012, vol. 25, no. 287 (22), pp. 18656–18673. https://doi.org/10.1074/jbc.M111.322883

  29. Huotari, J. and Helenius, A., Endosome maturation, EMBO J., 2011, vol. 30, no. 17, pp. 3481–3500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hur, Y., Feng, S., Wilson, K., et al., Embryonic stem cell-derived extracellular vesicles maintain ESC stemness by activating FAK, Dev. Cell, 2020. https://doi.org/10.1016/j.devcel.2020.11.017

  31. Hur, Y., Cerione, R., and Antonyak, M., Extracellular vesicles and their role in stem cell biology, Stem Cells, 2020, vol. 38, pp. 469–476.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Jae, N., McEwan, D., Manavski, Y., et al., Rab7a and Rab27b control secretion of endothelial microRNA through extracellular vesicles, FEBS Lett., 2015, vol. 589, no. 20, pp. 3182–3188.

    Article  CAS  PubMed  Google Scholar 

  33. Jeske, R., Bejoy, J., Marzano, M., et al., Human pluripotent stem cell-derived extracellular vesicles: characteristics and applications, Tissue Eng., 2020, vol. 26, no. 2.https://doi.org/10.1089/ten.teb.2019.0252

  34. Jung, J., Fu, X., and Yang, P., Exosomes generated from iPSC-derivatives: new direction for stem cell therapy in human heart diseases, Circ. Res., 2017, vol. 120, no. 2, pp. 407–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kalra, H., Drummen, G., and Mathivanan, S., Focus on extracellular vesicles: introducing the next small big thing, Int. J. Mol. Sci., 2016, vol. 17, no. 170. https://doi.org/10.3390/ijms17020170

  36. Konala, V., Mamidi, M., Bhonde, R., et al., The current landscape of the mesenchymal stromal cell secretome: a new paradigm for cell-free regeneration, Cytotherapy, 2016, vol. 18, no. 1, pp. 13–24.

    Article  CAS  PubMed  Google Scholar 

  37. Kowal, J., Tkach, M., and Thery, C., Biogenesis and secretion of exosomes, Curr. Opin. Cell Biol., 2014, vol. 29, pp. 116–125.

    Article  CAS  PubMed  Google Scholar 

  38. Kurian, N. and Modi, D., Extracellular vesicle mediated embryo–endometrial cross talk during implantation and in pregnancy, J. Assist. Reprod. Genet., 2019, vol. 36, pp. 189–198.

    Article  PubMed  Google Scholar 

  39. Latifkar, A., Hur, Y., Sanchez, J., et al., New insights into extracellular vesicle biogenesis and function, J. Cell Sci., 2019, vol. 132, no. 13. https://doi.org/10.1242/jcs.222406

  40. Li, S., Lin, Z., Jiang, X., et al., Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools, Acta Pharmacol. Sin., 2018, vol. 39, no. 4, pp. 542–551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Madrigal, M., Rao, K., and Riordan, N., A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods, J. Transl. Med., 2014, vol. 12, p. 260.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Marzano, M., Bejoy, J., Cheerathodi, M., et al., Differential effects of extracellular vesicles of lineage-specific human pluripotent stem cells on the cellular behaviors of isogenic cortical spheroids, Cells, 2019, vol. 8, p. 993. https://doi.org/10.3390/cells8090993

    Article  CAS  PubMed Central  Google Scholar 

  43. McGough, I. and Vincent, J.-P., Exosomes in developmental signalling, Development, 2016, vol. 143, pp. 2482–2493. https://doi.org/10.1242/dev.126516

    Article  CAS  PubMed  Google Scholar 

  44. Mendell, J., miRiad roles for the miR-17-92 cluster in development and disease, Cell, 2008, vol. 133, pp. 217–222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Michalke, W. and Loewenstein, W., Communication between cells of different type, Nature, 1971, vol. 232, no. 5306, pp. 121–122.

    Article  CAS  PubMed  Google Scholar 

  46. Mughees, M., Chung, H., and Wajid, S., Vesicular trafficking-related proteins as the potential therapeutic target for breast cancer, Protoplasma, 2020, vol. 257, no. 2, pp. 345–352.

    Article  CAS  PubMed  Google Scholar 

  47. Muhsin-Sharafaldine, M. and McLellan, A., Apoptotic vesicles: deathly players in cancer-associated coagulation, Immunol. Cell. Biol., 2018.

  48. Oh, M., Lee, J., Kim, Y., et al., Exosomes derived from human induced pluripotent stem cells ameliorate the aging of skin fibroblasts, Int. J. Mol. Sci., 2018, vol. 19, no. 6, p. 1715. https://doi.org/10.3390/ijms19061715

    Article  CAS  PubMed Central  Google Scholar 

  49. Panteleev, M.A., Abaeva, A.A., Nechipurenko, D.Yu., et al., Physiology and pathology of extracellular vesicles, Onkogematologiya, 2017, vol. 12, no. 1, pp. 62–70.

    Article  Google Scholar 

  50. Povero, D., Pinatel, E., Leszczynska, A., et al., Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis, JCI Insight., 2019, vol. 5, no. 4.

  51. Rani, S., Ryan, A., Griffin, M., et al., Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications, Mol. Ther., 2015, vol. 23, no. 5, pp. 812–823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Raposo, G. and Stahl, P., Extracellular vesicles: a new communication paradigm?, Nat. Rev. Mol. Cell. Biol., 2019, vol. 20, no. 9, pp. 509–510.

    Article  CAS  PubMed  Google Scholar 

  53. Rashed, M., Kanlikilicer, P., Rodriguez-Aguayo, C., et al., Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs, Oncotarget, 2017, vol. 8, no. 12, pp. 20145–20164.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ratajczak, J., Miekus, K., Kucia, M., et al., Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mrna and protein delivery, Leukemia, 2006, vol. 20, no. 5, pp. 847–856.

    Article  CAS  PubMed  Google Scholar 

  55. Rodin, S., Domogatskaya, A., Strom, S., et al., Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511, Nat. Biotechnol., 2010, vol. 28, no. 6, pp. 611–615.

    Article  CAS  PubMed  Google Scholar 

  56. Santoso, M., Ikeda, G., Tada, Y., et al., Exosomes from induced pluripotent stem cell-derived cardiomyocytes promote autophagy for myocardial repair, J. Am. Heart. Assoc., 2020, vol. 9, no. 6.

  57. Sayed, D. and Abdellatif, M., MicroRNAs in development and disease, Physiol. Rev., 2011, vol. 91, pp. 827–887.

    Article  CAS  PubMed  Google Scholar 

  58. Sharma, P., Mesci, P., Carromeu, C., et al., Exosomes regulate neurogenesis and circuit assembly, Proc. Natl. Acad. Sci. USA, 2019, vol. 116, no. 32, pp. 16086–16094.

  59. Sheldon, H., Heikamp, E., Turley, H., et al., New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes, Blood, 2010, vol. 116, pp. 2385–2394. https://doi.org/10.1182/blood-2009-08-239228

    Article  CAS  PubMed  Google Scholar 

  60. Sun, Z., Li, F., Zhou, X., et al., Stem cell therapies for chronic obstructive pulmonary disease: current status of pre-clinical studies and clinical trials, J. Thorac. Dis., 2018, vol. 10, no. 2, pp. 1084–1098. https://doi.org/10.21037/jtd.2018.01.46

    Article  PubMed  PubMed Central  Google Scholar 

  61. Taheri, B., Soleimani, M., Aval, S., et al., Induced pluripotent stem cell-derived extracellular vesicles: a novel approach for cell-free regenerative medicine, J. Cell Physiol., 2019, vol. 234, no. 6, pp. 8455–8464.

    Article  CAS  PubMed  Google Scholar 

  62. Tamkovich, S.N., Tutanov, O.S., and Laktionov, P.P., Exosomes: mechanisms, occurrence, composition, transport, biological activity, use in diagnostics, Biol. Membr., 2016, vol. 33, no. 1, pp. 163–175.

    CAS  Google Scholar 

  63. Terashvili, M. and Bosnjak, J., Stem cell therapies in cardiovascular disease, J. Cardiothor. Vasc. Anesth., 2019, vol. 33, no. 1, pp. 209–222.

    Article  Google Scholar 

  64. Tesar, P., Chenoweth, J., Brook, F., et al., New cell lines from mouse epiblast share defining features with human embryonic stem cells, Nature, 2007, vol. 12, no. 448 (7150), pp. 196–199.

  65. Thakur, B., Zhang, H., Becker, A., et al., Double-stranded DNA in exosomes: a novel biomarker in cancer detection, Cell Res., 2014, vol. 24, pp. 766–769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Theos, A., Truschel, S., Tenza, D., et al., A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis, Dev. Cell, 2006, vol. 10, no. 3, pp. 343–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Theunissen, T., Powell, B., Wang, H., et al., Systematic identification of culture conditions for induction and maintenance of naive human pluripotency, Cell. Stem. Cell, 2014, vol. 2, no. 15 (4), pp. 471–487.

  68. Toya, S., Wary, K., Mittal, M., et al., Integrin α6β1 expressed in ESCs instructs the differentiation to endothelial cells, Stem. Cells, 2015, vol. 33, no. 6, pp. 1719–1729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Villa-Diaz, L., Kim, J., Laperle, A., et al., Inhibition of focal adhesion kinase signaling by integrin α6β1 supports human pluripotent stem cell self-renewal, Stem Cells, 2016, vol. 34, no. 7, pp. 1753–1764.

    Article  CAS  PubMed  Google Scholar 

  70. Vitillo, L. and Kimber, S., Integrin and FAK regulation of human pluripotent stem cells, Curr. Stem. Cell. Rep., 2017, vol. 3, no. 4, pp. 358–365. https://doi.org/10.1007/s40778-017-0100-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Vitillo, L., Baxter, M., Iskender, B., et al., Integrin-associated adhesion kinase protects human embryonic stem cells from apoptosis, detachment and differentiation, Stem. Cell. Rep., 2016, vol. 7, pp. 167–176.

    Article  CAS  Google Scholar 

  72. Vyas, N., Walvekar, A., Tate, D., et al., Vertebrate hedgehog is secreted on two types of extracellular vesicles with different signaling properties, Sci. Rep., 2014, vol. 4, p. 7357. https://doi.org/10.1038/srep0735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wang, Y., Zhang, L., Li, Y., et al., Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium, J. Cardiol., 2015, vol. 192, no. 61.

  74. Wolf, P., The nature and significance of platelet products in human plasma, Br. J. Haematol., 1967, vol. 13, no. 3, pp. 269–288.

    Article  CAS  PubMed  Google Scholar 

  75. Yang, L., Peng, X., Li, Y., et al., Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma, Mol. Cancer, 2019, vol. 3, no. 1, p. 78.

    Article  Google Scholar 

  76. Yang, X., Meng, Y., Han, Z., et al., Mesenchymal stem cell therapy for liver disease: full of chances and challenges, Cell Biosci., 2020, vol. 10, no. 123.

  77. Ye, M., Ni, Q., Qi, H., et al., Exosomes derived from human induced pluripotent stem cells-endothelia cells promotes postnatal angiogenesis in mice bearing ischemic limbs, Int. J. Biol. Sci., 2019, vol. 15, no. 1, pp. 158–168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhang, Y., Liu, Y., Liu, H., et al., Exosomes: biogenesis, biologic function and clinical potential, Cell Biosci., 2019, vol. 15, no. 9, p. 19.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGEMENTS

We thank Professor Vladimir Alexandrovich Golichenkov and the leading researcher Olga Vladimirovna Burlakova for discussion and valuable comments.

Funding

The work was carried out with the financial support of the Russian Foundation for Basic Research, project no. 19-29-04136mk.

Author information

Authors and Affiliations

  1. Faculty of Biology, Moscow State University, 119234, Moscow, Russia

    E. A. Suprunenko, E. A. Sazonova & A. V. Vasiliev

  2. Koltsov Institute of Developmental Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    A. V. Vasiliev

Authors
  1. E. A. Suprunenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. A. Sazonova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Vasiliev
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors made the same contribution to the preparation and writing of this review.

Corresponding author

Correspondence to E. A. Suprunenko.

Ethics declarations

The authors declare that they have no conflict of interests. This review does not contain any studies involving human participants or laboratory animals as experimental models performed by the authors.

Additional information

Translated by A. Ermakov

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suprunenko, E.A., Sazonova, E.A. & Vasiliev, A.V. Extracellular Vesicles of Pluripotent Stem Cells. Russ J Dev Biol 52, 129–140 (2021). https://doi.org/10.1134/S1062360421030073

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062360421030073

Keywords:

Search

Navigation