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Cited by 109Extracellular vesicles in diseaseMesenchymal stem cell researchPeriodontal Regeneration and Treatments

Applications, challenges and prospects of mesenchymal stem cell exosomes in regenerative medicine

Open access
Rezabakhsh, Aysa, Sokullu, Emel, Rahbarghazi, Reza·2021·Stem Cell Research & Therapy
DOI 10.1186/s13287-021-02596-zPMC PMC8478268
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Abstract

Recent advances in the identification and application of different stem cell types have offered alternative therapeutic approaches for clinicians. The lack of successful engraftment, migration into the injured site, loss of functionality and viability, ethical issues, shortage of donated allogeneic stem cells and the possibility of transmission of infectious are the main challenges associated with direct cell transplantation. The discovery and research on exosomes have led to the rise of hopes for the alleviation of different pathologies in regenerative medicine. Exo are nano-sized extracellular vesicles (40–150 nm) and released by each type. These nanoparticles participate in cell-to-cell communication in a paracrine manner. It is thought that the application of Exo can circumvent several drawbacks related to whole-cell therapies. Because of their appropriate size and stability, Exo are touted as therapeutic bullets transferring signaling factors into the acceptor cells in a paracrine manner. Despite these advantages, technologies associated with Exo isolation and purification are challenging because of heterogeneity in exosomal size and cargo. The lack of standard GMP-grade protocols is the main hurdle that limits the extensive application of Exo in the clinical setting. Here, the authors aimed to inspire a logical and realistic vision about problems associated with Exo application in regenerative medicine.

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  • The risk of thrombosis from MSC-EVs cannot be ignored, especially for higher concentrations, due to the presence of procoagulant factors when systemically administered.

    “Nevertheless, the risk of thrombosis cannot be ignored, especially for higher concentrations, due to the presence of procoagulant factors when systemically administered [241], [257].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [241]

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Research works printed but not linked: 36

  1. [1]Rahbarghazi R Nassiri SM Khazraiinia P Kajbafzadeh A-M Ahmadi SH Mohammadi E Molazem M Zamani-Ahmadmahmudi M Juxtacrine and paracrine interactions of rat marrow-derived mesenchymal stem cells, muscle-derived satellite cells, and neonatal cardiomyocytes with endothelial cells in angiogenesis dynamics Stem Cells Dev 2013 22 6 855 865 10.1089/scd.2012.0377 23072248 PMC3585743 · DOI
  2. [2]Mirershadi F Ahmadi M Rezabakhsh A Rajabi H Rahbarghazi R Keyhanmanesh R Unraveling the therapeutic effects of mesenchymal stem cells in asthma Stem Cell Res Ther 2020 11 1 400 10.1186/s13287-020-01921-2 32933587 PMC7493154 · DOI
  3. [3]Yang Y-HK Ogando CR Wang See C Chang T-Y Barabino GA Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro Stem Cell Res Ther 2018 9 1 131 131 10.1186/s13287-018-0876-3 29751774 PMC5948736 · DOI
  4. [4]Mitrousis N Fokina A Shoichet MS Biomaterials for cell transplantation Nat Rev Mater 2018 3 11 441 456 10.1038/s41578-018-0057-0 · DOI
  5. [5]Amini H Rezabakhsh A Heidarzadeh M Hassanpour M Hashemzadeh S Ghaderi S Sokullu E Rahbarghazi R Reiter RJ An examination of the putative role of melatonin in exosome biogenesis Front Cell Dev Biol 2021 9 1396 10.3389/fcell.2021.686551 PMC8219171 34169078 · DOI
  6. [7]Angulski AB Capriglione LG Batista M Marcon BH Senegaglia AC Stimamiglio MA Correa A The protein content of extracellular vesicles derived from expanded human umbilical cord blood-derived CD133+ and human bone marrow-derived mesenchymal stem cells partially explains why both sources are advantageous for regenerative medicine Stem Cell Rev Rep 2017 13 2 244 257 10.1007/s12015-016-9715-z 28054239 · DOI
  7. [8]Bagheri HS Mousavi M Rezabakhsh A Rezaie J Rasta SH Nourazarian A Avci ÇB Tajalli H Talebi M Oryan A Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling Lasers Med Sci 2018 33 5 1131 1145 10.1007/s10103-018-2495-8 29603107 · DOI
  8. [9]Moghadasi S Elveny M Rahman HS Suksatan W Jalil AT Abdelbasset WK Yumashev AV Shariatzadeh S Motavalli R Behzad F Marofi F Hassanzadeh A Pathak Y Jarahian M A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine J Transl Med 2021 19 1 302 10.1186/s12967-021-02980-6 34253242 PMC8273572 · DOI
  9. [10]Dabrowska S Andrzejewska A Janowski M Lukomska B Immunomodulatory and regenerative effects of mesenchymal stem cells and extracellular vesicles: therapeutic outlook for inflammatory and degenerative diseases Front Immunol 2021 11 3809 10.3389/fimmu.2020.591065 PMC7893976 33613514 · DOI
  10. [11]Marbán E The secret life of exosomes: what bees can teach us about next-generation therapeutics J Am Coll Cardiol 2018 71 2 193 200 10.1016/j.jacc.2017.11.013 29325643 PMC5769161 · DOI
  11. [12]Jabbari N Akbariazar E Feqhhi M Rahbarghazi R Rezaie J Breast cancer-derived exosomes: tumor progression and therapeutic agents J Cell Physiol 2020 235 10 6345 6356 10.1002/jcp.29668 32216070 · DOI
  12. [13]Li X Corbett AL Taatizadeh E Tasnim N Little JP Garnis C Daugaard M Guns E Hoorfar M Li ITS Challenges and opportunities in exosome research—perspectives from biology, engineering, and cancer therapy APL Bioeng 2019 3 1 011503 011503 10.1063/1.5087122 31069333 PMC6481742 · DOI
  13. [14]Raposo G Stoorvogel W Extracellular vesicles: exosomes, microvesicles, and friends J Cell Biol 2013 200 4 373 383 10.1083/jcb.201211138 23420871 PMC3575529 · DOI · Paper page
  14. [15]Yang D Zhang W Zhang H Zhang F Chen L Ma L Larcher LM Chen S Liu N Zhao Q Progress, opportunity, and perspective on exosome isolation-efforts for efficient exosome-based theranostics Theranostics 2020 10 8 3684 10.7150/thno.41580 32206116 PMC7069071 · DOI
  15. [16]Li P Kaslan M Lee SH Yao J Gao Z Progress in exosome isolation techniques Theranostics 2017 7 3 789 10.7150/thno.18133 28255367 PMC5327650 · DOI
  16. [17]Van Deun J Mestdagh P Sormunen R Cocquyt V Vermaelen K Vandesompele J Bracke M De Wever O Hendrix A The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling J Extracell Vesicles 2014 3 1 24858 10.3402/jev.v3.24858 PMC4169610 25317274 · DOI
  17. [18]Haraszti RA Miller R Stoppato M Sere YY Coles A Didiot MC Wollacott R Sapp E Dubuke ML Li X Shaffer SA DiFiglia M Wang Y Aronin N Khvorova A Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity Mol Ther J Am Soc Gene Ther 2018 26 12 2838 2847 10.1016/j.ymthe.2018.09.015 PMC6277553 30341012 · DOI · Paper page
  18. [19]Lőrincz ÁM Timár CI Marosvári KA Veres DS Otrokocsi L Kittel Á Ligeti E Effect of storage on physical and functional properties of extracellular vesicles derived from neutrophilic granulocytes J Extracell Vesicles 2014 3 1 25465 10.3402/jev.v3.25465 25536933 PMC4275651 · DOI
  19. [20]Lee M Ban J-J Im W Kim M Influence of storage condition on exosome recovery Biotechnol Bioprocess Eng 2016 21 2 299 304 10.1007/s12257-015-0781-x · DOI
  20. [21]Pedrioli G Piovesana E Vacchi E Balbi C Extracellular vesicles as promising carriers in drug delivery: considerations from a cell biologist’s perspective Biology 2021 10 5 376 10.3390/biology10050376 33925620 PMC8145252 · DOI
  21. [22]Cheng Y Zeng Q Han Q Xia W Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes Protein Cell 2019 10 4 295 299 10.1007/s13238-018-0529-4 29616487 PMC6418301 · DOI · Paper page
  22. [23]Wiest EF Zubair AC Challenges of manufacturing mesenchymal stromal cell–derived extracellular vesicles in regenerative medicine Cytotherapy 2020 22 11 606 612 10.1016/j.jcyt.2020.04.040 32532592 · DOI
  23. [24]Patel DB Gray KM Santharam Y Lamichhane TN Stroka KM Jay SM Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles Bioeng Transl Med 2017 2 2 170 179 10.1002/btm2.10065 28932818 PMC5579732 · DOI
  24. [25]Ludwig N Whiteside TL Reichert TE Challenges in exosome isolation and analysis in health and disease Int J Mol Sci 2019 20 19 4684 10.3390/ijms20194684 PMC6801453 31546622 · DOI
  25. [26]Burger D Turner M Xiao F Munkonda MN Akbari S Burns KD High glucose increases the formation and pro-oxidative activity of endothelial microparticles Diabetologia 2017 60 9 1791 1800 10.1007/s00125-017-4331-2 28601907 · DOI
  26. [27]Liu Y Defourny KA Smid EJ Abee T Gram-positive bacterial extracellular vesicles and their impact on health and disease Front Microbiol 2018 9 1502 10.3389/fmicb.2018.01502 30038605 PMC6046439 · DOI
  27. [28]Rezaie J Aslan C Ahmadi M Zolbanin NM Kashanchi F Jafari R The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application Cell Biosci 2021 11 1 19 10.1186/s13578-021-00537-0 33451365 PMC7810184 · DOI
  28. [29]Silachev DN Goryunov KV Shpilyuk MA Beznoschenko OS Morozova NY Kraevaya EE Popkov VA Pevzner IB Zorova LD Evtushenko EA Effect of MSCs and MSC-derived extracellular vesicles on human blood coagulation Cells 2019 8 3 258 10.3390/cells8030258 PMC6468445 30893822 · DOI · Paper page
  29. [30]Kumar SR Kimchi ET Manjunath Y Gajagowni S Stuckel AJ Kaifi JT RNA cargos in extracellular vesicles derived from blood serum in pancreas associated conditions Sci Rep 2020 10 1 2800 10.1038/s41598-020-59523-0 32071328 PMC7028741 · DOI
  30. [31]Kerris EW Hoptay C Calderon T Freishtat RJ Platelets and platelet extracellular vesicles in hemostasis and sepsis J Invest Med 2020 68 4 813 820 10.1136/jim-2019-001195 31843956 · DOI
  31. [32]Chen Y Li G Liu Y Werth VP Williams KJ Liu ML Translocation of endogenous danger signal HMGB1 from nucleus to membrane microvesicles in macrophages J Cell Physiol 2016 231 11 2319 2326 10.1002/jcp.25352 26909509 PMC5021294 · DOI
  32. [33]Prunevieille A Babiker-Mohamed MH Aslami C Gonzalez-Nolasco B Mooney N Benichou G T cell antigenicity and immunogenicity of allogeneic exosomes Am J Transplant 2021 21 7 2583 2589 10.1111/ajt.16591 33794063 PMC10601455 · DOI
  33. [34]Cai XW Zhu R Ran L Li YQ Huang K Peng J He W Zhou CL Wang RP A novel non-contact communication between human keratinocytes and T cells: exosomes derived from keratinocytes support superantigen-induced proliferation of resting T cells Mol Med Rep 2017 16 5 7032 7038 10.3892/mmr.2017.7492 28901485 · DOI
  34. [35]Imai T Takahashi Y Nishikawa M Kato K Morishita M Yamashita T Matsumoto A Charoenviriyakul C Takakura Y Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice J Extracell Vesicles 2015 4 26238 26238 10.3402/jev.v4.26238 25669322 PMC4323410 · DOI
  35. [36]Sid-Otmane C Perrault LP Ly HQ Mesenchymal stem cell mediates cardiac repair through autocrine, paracrine and endocrine axes J Transl Med 2020 18 1 336 10.1186/s12967-020-02504-8 32873307 PMC7466793 · DOI
  36. [37]Heidarzadeh M Gürsoy-Özdemir Y Kaya M Abriz AE Zarebkohan A Rahbarghazi R Sokullu E Exosomal delivery of therapeutic modulators through the blood–brain barrier; promise and pitfalls Cell Biosci 2021 11 1 1 28 10.1186/s13578-021-00650-0 34294165 PMC8296716 · DOI

Cited by

Sorted by citations

Authors
Rezabakhsh, A., Sokullu, E., & Rahbarghazi, R.
Affiliations
  • Tabriz University of Medical Sciences (IR)
  • Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (TR)
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2021-09-28
Volume
12
Issue
1
Pages
521-521
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-021-02596-z
PMC
PMC8478268
OpenAlex
W3203149769
Cited by
109
References
1
Citations by year
2026: 20 · 2025: 25 · 2024: 23 · 2023: 20 · 2022: 20 · 2021: 1
FWCI
5.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Collections portal (Koç University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Tabriz University of Medical Sciences (IR.TBZMED.VCR.REC.1397.395)
  • National Institute for Medical Research Development (IR.NIMAD.REC.1397.512)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
mesenchymal stem cell-derived exosomes, extracellular vesicles, regenerative medicine, cell-free therapy, paracrine signaling, exosome isolation and purification, exosome heterogeneity
MeSH terms
Extracellular Vesicles, Stem Cells, Regenerative Medicine, Exosomes, Mesenchymal Stem Cells

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