Analyze Diet
Animals : an open access journal from MDPI2024; 14(15); 2147; doi: 10.3390/ani14152147

Therapeutic Application of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Domestic Animals.

Abstract: Recently, the therapeutic potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) has been extensively studied in both human and veterinary medicine. EVs are nano-sized particles containing biological components commonly found in other biological materials. For that reason, EV isolation and characterization are critical to draw precise conclusions during their investigation. Research on EVs within veterinary medicine is still considered in its early phases, yet numerous papers were published in recent years. The conventional adult tissues for deriving MSCs include adipose tissue and bone marrow. Nonetheless, alternative sources such as synovial fluid, endometrium, gingiva, and milk have also been intermittently used. Fetal adnexa are amniotic membrane/fluid, umbilical cord and Wharton's jelly. Cells derived from fetal adnexa exhibit an intermediate state between embryonic and adult cells, demonstrating higher proliferative and differentiative potential and longer telomeres compared to cells from adult tissues. Summarized here are the principal and recent preclinical and clinical studies performed in domestic animals such as horse, cattle, dog and cat. To minimize the use of antibiotics and address the serious issue of antibiotic resistance as a public health concern, they will undoubtedly also be utilized in the future to treat infections in domestic animals. A number of concerns, including large-scale production with standardization of EV separation and characterization techniques, must be resolved for clinical application.
Publication Date: 2024-07-24 PubMed ID: 39123673PubMed Central: PMC11310970DOI: 10.3390/ani14152147Google 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.
  • Journal Article
  • Review

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.

Therapeutic use of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) shows promising potential for treating diseases in domestic animals like horses, cattle, dogs, and cats. This research reviews recent studies and discusses challenges in isolating and standardizing EVs for veterinary clinical applications.

Introduction to Extracellular Vesicles and Mesenchymal Stem Cells

  • Extracellular vesicles (EVs) are tiny particles released by cells containing proteins, lipids, and nucleic acids, playing roles in intercellular communication.
  • Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into various cell types and secrete EVs with therapeutic properties.
  • EVs derived from MSCs can mimic beneficial effects of stem cell therapy without the risks related to cell transplantation.
  • EVs are found in multiple biological materials, necessitating precise isolation and characterization methods to ensure purity and functionality.

Sources of Mesenchymal Stem Cells for EV Production

  • Traditional adult tissue sources for MSC isolation include:
    • Adipose (fat) tissue
    • Bone marrow
  • Alternative tissue sources that have been explored:
    • Synovial fluid (joint fluid)
    • Endometrium (lining of the uterus)
    • Gingiva (gum tissue)
    • Milk
  • Fetal adnexa-derived MSCs come from:
    • Amniotic membrane and fluid
    • Umbilical cord
    • Wharton’s jelly (a gelatinous substance inside the umbilical cord)
  • Fetal adnexa MSCs:
    • Are intermediate between embryonic and adult stem cells
    • Show higher proliferation and differentiation capabilities
    • Have longer telomeres, indicating potentially greater replicative lifespan

Current Research and Applications in Veterinary Medicine

  • Research involving EVs from MSCs is still in early stages in veterinary medicine, though the number of publications has increased recently.
  • Domestic animals studied include:
    • Horses
    • Cattle
    • Dogs
    • Cats
  • Preclinical and clinical studies have evaluated the safety and efficacy of MSC-derived EVs for various conditions in these animals.
  • Potential therapeutic uses include:
    • Wound healing and tissue regeneration
    • Modulation of immune responses
    • Treatment of inflammatory diseases
    • Antimicrobial therapy to reduce reliance on antibiotics

Implications for Antibiotic Resistance and Future Uses

  • Reducing the use of antibiotics in domestic animals is critical to combat increasing antibiotic resistance, a major public health concern.
  • MSC-derived EVs may serve as alternatives or adjuncts to antibiotics by enhancing immune defense or exerting direct antimicrobial effects.
  • This application could have significant benefits for animal health and food safety.

Challenges and Considerations for Clinical Application

  • Large-scale production of EVs that meet clinical-grade quality is challenging.
  • Standardization is needed for:
    • EV isolation methods to ensure purity and yield
    • EV characterization techniques for consistent identification and potency assessment
    • Storage and delivery methods preserving EV functionality
  • Regulatory frameworks specific to veterinary applications must be developed.
  • Further studies are required to establish optimal dosages, safety profiles, and long-term effects in different domestic animal species.

Conclusion

  • MSC-derived extracellular vesicles represent a promising novel therapeutic approach in veterinary medicine.
  • They hold potential not only for regenerative medicine but also as an antimicrobial alternative to reduce antibiotic use.
  • Future research should focus on overcoming production and standardization challenges to enable broad clinical use in domestic animals.

Cite This Article

APA
Lanci A, Iacono E, Merlo B. (2024). Therapeutic Application of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Domestic Animals. Animals (Basel), 14(15), 2147. https://doi.org/10.3390/ani14152147

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 14
Issue: 15
PII: 2147

Researcher Affiliations

Lanci, Aliai
  • Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sora 50, Ozzano dell'Emilia, 40064 Bologna, Italy.
Iacono, Eleonora
  • Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sora 50, Ozzano dell'Emilia, 40064 Bologna, Italy.
  • Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40100 Bologna, Italy.
Merlo, Barbara
  • Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sora 50, Ozzano dell'Emilia, 40064 Bologna, Italy.
  • Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40100 Bologna, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 171 references
  1. Lalu M.M., McIntyre L., Pugliese C., Fergusson D., Winston B.W., Marshall J.C., Granton J., Stewart D.J., Canadian Critical Care Trials Group. Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials. PLoS ONE 2012;7:e47559.
  2. Brooke G., Cook M., Blair C., Han R., Heazlewood C., Jones B., Kambouris M., Kollar K., McTaggart S., Pelekanos R.. Therapeutic Applications of Mesenchymal Stromal Cells. Semin. Cell Dev. Biol. 2007;18:846–858.
    doi: 10.1016/j.semcdb.2007.09.012pubmed: 18024097google scholar: lookup
  3. Iacono E., Pascucci L., Rossi B., Bazzucchi C., Lanci A., Ceccoli M., Merlo B.. Ultrastructural characteristics and immune profile of equine MSCs from fetal adnexa. Reproduction 2017;154:509–519.
    doi: 10.1530/REP-17-0032pubmed: 28733347google scholar: lookup
  4. Merlo B., Teti G., Lanci A., Burk J., Mazzotti E., Falconi M., Iacono E.. Comparison between Adult and Foetal Adnexa Derived Equine Post-Natal Mesenchymal Stem Cells. BMC Vet. Res. 2019;15:277.
    doi: 10.1186/s12917-019-2023-5pmc: PMC6679462pubmed: 31375144google scholar: lookup
  5. Hofmann N.A., Ortner A., Jacamo R.O., Reinisch A., Schallmoser K., Rohban R., Etchart N., Fruehwirth M., Beham-Schmid C., Andreeff M.. Oxygen Sensing Mesenchymal Progenitors Promote Neo-Vasculogenesis in a Humanized Mouse Model In Vivo. PLoS ONE 2012;7:e44468.
  6. Bell G.I., Meschino M.T., Hughes-Large J.M., Broughton H.C., Xenocostas A., Hess D.A.. Combinatorial Human Progenitor Cell Transplantation Optimizes Islet Regeneration Through Secretion of Paracrine Factors. Stem Cells Dev. 2012;21:1863–1876.
    doi: 10.1089/scd.2011.0634pubmed: 22309189google scholar: lookup
  7. Abumaree M.H., Abomaray F.M., Alshabibi M.A., AlAskar A.S., Kalionis B.. Immunomodulatory Properties of Human Placental Mesenchymal Stem/Stromal Cells. Placenta 2017;59:87–95.
  8. Carrade D.D., Borjesson D.L.. Immunomodulation by Mesenchymal Stem Cells in Veterinary Species. Comp. Med. 2013;63:207–217.
    pmc: PMC3690426pubmed: 23759523
  9. Le Blanc K., Davies L.C.. Mesenchymal Stromal Cells and the Innate Immune Response. Immunol. Lett. 2015;168:140–146.
    doi: 10.1016/j.imlet.2015.05.004pubmed: 25982165google scholar: lookup
  10. Zhao S., Wehner R., Bornhäuser M., Wassmuth R., Bachmann M., Schmitz M.. Immunomodulatory Properties of Mesenchymal Stromal Cells and Their Therapeutic Consequences for Immune-Mediated Disorders. Stem Cells Dev. 2010;19:607–614.
    doi: 10.1089/scd.2009.0345pubmed: 19824807google scholar: lookup
  11. Raposo G., Stoorvogel W.. Extracellular Vesicles: Exosomes, Microvesicles, and Friends. J. Cell Biol. 2013;200:373–383.
    doi: 10.1083/jcb.201211138pmc: PMC3575529pubmed: 23420871google scholar: lookup
  12. Yáñez-Mó M., Siljander P.R.M., Andreu Z., Bedina Zavec A., Borràs F.E., Buzas E.I., Buzas K., Casal E., Cappello F., Carvalho J.. Biological Properties of Extracellular Vesicles and Their Physiological Functions. J. Extracell. Vesicles. 2015;4:27066.
    doi: 10.3402/jev.v4.27066pmc: PMC4433489pubmed: 25979354google scholar: lookup
  13. George J.N., Thoi L.L., McManus L.M., Reimann T.A.. Isolation of Human Platelet Membrane Microparticles from Plasma and Serum. Blood 1982;60:834–840.
    doi: 10.1182/blood.V60.4.834.834pubmed: 7115953google scholar: lookup
  14. Ratajczak J., Wysoczynski M., Hayek F., Janowska-Wieczorek A., Ratajczak M.Z.. Membrane-Derived Microvesicles: Important and Underappreciated Mediators of Cell-to-Cell Communication. Leukemia 2006;20:1487–1495.
    doi: 10.1038/sj.leu.2404296pubmed: 16791265google scholar: lookup
  15. Akyurekli C., Le Y., Richardson R.B., Fergusson D., Tay J., Allan D.S.. A Systematic Review of Preclinical Studies on the Therapeutic Potential of Mesenchymal Stromal Cell-Derived Microvesicles. Stem Cell Rev. 2015;11:150–160.
    doi: 10.1007/s12015-014-9545-9pubmed: 25091427google scholar: lookup
  16. Rani S., Ryan A.E., Griffin M.D., Ritter T. Mesenchymal Stem Cell-Derived Extracellular Vesicles: Toward Cell-Free Therapeutic Applications. Mol. Ther. 2015;23:812–823. doi: 10.1038/mt.2015.44.
    doi: 10.1038/mt.2015.44pmc: PMC4427881pubmed: 25868399google scholar: lookup
  17. Théry C., Witwer K.W., Aikawa E., Alcaraz M.J., Anderson J.D., Andriantsitohaina R., Antoniou A., Arab T., Archer F., Atkin-Smith G.K., 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;7:1535750. doi: 10.1080/20013078.2018.1535750.
  18. Lee J.K., Park S.R., Jung B.K., Jeon Y.K., Lee Y.S., Kim M.K., Kim Y.G., Jang J.Y., Kim C.W. Exosomes Derived from Mesenchymal Stem Cells Suppress Angio-genesis by Down-Regulating VEGF Expression in Breast Cancer Cells. PLoS ONE. 2013;8:e84256. doi: 10.1371/journal.pone.0084256.
  19. Roccaro A.M., Sacco A., Maiso P., Azab A.K., Tai Y.T., Reagan M., Azab F., Flores L.M., Campigotto F., Weller E., et al. BM mesenchymal stromal cell–derived exosomes facilitate multiple myeloma progression. J. Clin. Investig. 2012;123:1542–1555. doi: 10.1172/JCI66517.
    doi: 10.1172/JCI66517pmc: PMC3613927pubmed: 23454749google scholar: lookup
  20. Im H., Shao H., Park Y.I., Peterson V.M., Castro C.M., Weissleder R., Lee H. Label-Free Detection and Molecular Profiling of Exosomes with a Nano-Plasmonic Sensor. Nat. Biotechnol. 2014;32:490–495. doi: 10.1038/nbt.2886.
    doi: 10.1038/nbt.2886pmc: PMC4356947pubmed: 24752081google scholar: lookup
  21. Caplan A.I., Dennis J.E. Mesenchymal Stem Cells as Trophic Mediators. J. Cell Biochem. 2006;98:1076–1084. doi: 10.1002/jcb.20886.
    doi: 10.1002/jcb.20886pubmed: 16619257google scholar: lookup
  22. Ratajczak M.Z. The Emerging Role of Microvesicles in Cellular Therapies for Organ/Tissue Regeneration. Nephrol. Dial. Transpl. 2011;26:1453–1456. doi: 10.1093/ndt/gfr165.
    doi: 10.1093/ndt/gfr165pubmed: 21531733google scholar: lookup
  23. Pan B.T., Johnstone R.M. Fate of the Transferrin Receptor during Maturation of Sheep Reticulocytes in Vitro: Selective Externalization of the Receptor. Cell. 1983;33:967–978. doi: 10.1016/0092-8674(83)90040-5.
    doi: 10.1016/0092-8674(83)90040-5pubmed: 6307529google scholar: lookup
  24. Wang Y., Wen J., Lu T., Han W., Jiao K., Li H. Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists. Int. J. Nanomed. 2024;19:3233–3257. doi: 10.2147/IJN.S441467.
    doi: 10.2147/IJN.S441467pmc: PMC11005933pubmed: 38601346google scholar: lookup
  25. Mathieu M., Martin-Jaular L., Lavieu G., Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to- cell communication. Nat. Cell Biol. 2019;21:9–17. doi: 10.1038/s41556-018-0250-9.
    doi: 10.1038/s41556-018-0250-9pubmed: 30602770google scholar: lookup
  26. van Niel G., Carter D.R.F., Clayton A., Lambert D.W., Raposo G., Vader P. Challenges and directions in studying cell-cell communication by extracellular vesicles. Nat. Rev. Mol. Cell Biol. 2022;23:369–382. doi: 10.1038/s41580-022-00460-3.
    doi: 10.1038/s41580-022-00460-3pubmed: 35260831google scholar: lookup
  27. Varderidou-Minasian S., Lorenowicz M.J. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: Challenges and opportunities. Theranostics. 2020;10:5979–5997. doi: 10.7150/thno.40122.
    doi: 10.7150/thno.40122pmc: PMC7254996pubmed: 32483432google scholar: lookup
  28. Sluijter J.P., Verhage V., Deddens J.C., van den Akker F., Doevendans P.A. Microvesicles and exosomes for intracardiac communication. Cardiovasc. Res. 2014;102:302–311. doi: 10.1093/cvr/cvu022.
    doi: 10.1093/cvr/cvu022pubmed: 24488559google scholar: lookup
  29. Bian S., Zhang L., Duan L., Wang X., Min Y., Yu H. Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model. J. Mol. Med. 2014;92:387–397. doi: 10.1007/s00109-013-1110-5.
    doi: 10.1007/s00109-013-1110-5pubmed: 24337504google scholar: lookup
  30. Khoei S.G., Dermani F.K., Malih S., Fayazi N., Sheykhhasan M. The use of mesenchymal stem cells and their derived extracellular vesicles in cardiovascular disease treatment. Curr. Stem Cell Res. Ther. 2020;15:623–638. doi: 10.2174/1574888X15666200501235201.
  31. Bruno S., Grange C., Collino F., Deregibus M.C., Cantaluppi V., Biancone L., Tetta C., Camussi G. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS ONE. 2012;7:e33115. doi: 10.1371/journal.pone.0033115.
  32. Kilpinen L., Impola U., Sankkila L., Ritamo I., Aatonen M., Kilpinen S., Tuimala J., Valmu L., Levijoki J., Finckenberg P. Extracellular membrane vesicles from umbilical cord blood-derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning. J. Extracell. Vesicles. 2013;2:21927. doi: 10.3402/jev.v2i0.21927.
    doi: 10.3402/jev.v2i0.21927pmc: PMC3860334pubmed: 24349659google scholar: lookup
  33. Sun X., Meng H., Wan W., Xie M., Wen C. Application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases. Curr. Stem Cell Res. Ther. 2019;10:8. doi: 10.1186/s13287-018-1097-5.
    doi: 10.1186/s13287-018-1097-5pmc: PMC6323814pubmed: 30616603google scholar: lookup
  34. Mardpour S., Hassani S.N., Mardpour S., Sayahpour F., Vosough M., Ai J., Aghdami N., Hamidieh A.A., Baharvand H. Extra-cellular vesicles derived from human embryonic stem cell-MSCs ameliorate cirrhosis in thioacetamide-induced chronic liver injury. J. Cell Physiol. 2018;233:9330–9344. doi: 10.1002/jcp.26413.
    doi: 10.1002/jcp.26413pubmed: 29266258google scholar: lookup
  35. Wu R., Fan X., Wang Y., Shen M., Zheng Y., Zhao S., Yang L. Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver immunity and therapy. Front. Immunol. 2022;13:833878. doi: 10.3389/fimmu.2022.833878.
    doi: 10.3389/fimmu.2022.833878pmc: PMC8930843pubmed: 35309311google scholar: lookup
  36. Du Y.M., Zhuansun Y.X., Chen R., Lin L., Lin Y., Li J.G. Mesenchymal stem cell exosomes promote immunosuppression of regulatory T cells in asthma. Exp. Cell Res. 2018;363:114–120. doi: 10.1016/j.yexcr.2017.12.021.
    doi: 10.1016/j.yexcr.2017.12.021pubmed: 29277503google scholar: lookup
  37. Nataliya B., Mikhail A., Vladimir P., Olga G., Maksim V., Ivan Z., Novoseletskaya E., Sagaradze G., Danilova N., Malkov P., et al. Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer. Exp. Mol. Med. 2023;55:1399–1412. doi: 10.1038/s12276-023-01017-w.
    doi: 10.1038/s12276-023-01017-wpmc: PMC10393964pubmed: 37394579google scholar: lookup
  38. Casado-Díaz A., Quesada-Gómez J.M., Dorado G. Extracellular vesicles derived from mesenchymal stem cells (MSC) in regenerative medicine: Applications in skin wound healing. Front. Bioeng. Biotechnol. 2020;8:146. doi: 10.3389/fbioe.2020.00146.
    doi: 10.3389/fbioe.2020.00146pmc: PMC7062641pubmed: 32195233google scholar: lookup
  39. Ha D.H., Kim H.K., Lee J., Kwon H.H., Park G.H., Yang S.H., Jung J.Y., Choi H., Lee J.H., Sung S., et al. Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells. 2020;9:1157. doi: 10.3390/cells9051157.
    doi: 10.3390/cells9051157pmc: PMC7290908pubmed: 32392899google scholar: lookup
  40. Kim J., Kim E.H., Lee H., Sung J.H., Bang O.Y. Clinical-Scale Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Wound Healing. Int. J. Mol. Sci. 2023;24:4273. doi: 10.3390/ijms24054273.
    doi: 10.3390/ijms24054273pmc: PMC10001880pubmed: 36901703google scholar: lookup
  41. Dong L., Pu Y., Zhang L., Qi Q., Xu L., Li W., Wei C., Wang X., Zhou S., Zhu J., et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410. Cell Death Dis. 2018;9:218. doi: 10.1038/s41419-018-0323-5.
    doi: 10.1038/s41419-018-0323-5pmc: PMC5833395pubmed: 29440630google scholar: lookup
  42. Zhao Q., Hai B., Kelly J., Wu S., Liu F. Extracellular vesicle mimics made from iPS cell-derived mesenchymal stem cells improve the treatment of metastatic prostate cancer. Stem Cell Res. Ther. 2021;12:29. doi: 10.1186/s13287-020-02097-5.
    doi: 10.1186/s13287-020-02097-5pmc: PMC7792192pubmed: 33413659google scholar: lookup
  43. Weng Z., Zhang B., Wu C., Yu F., Han B., Li B., Li L. Therapeutic roles of mesenchymal stem cell-derived extracellular vesi-cles in cancer. J. Hematol. Oncol. 2021;14:136. doi: 10.1186/s13045-021-01141-y.
    doi: 10.1186/s13045-021-01141-ypmc: PMC8414028pubmed: 34479611google scholar: lookup
  44. Mathew B., Torres L.A., Gamboa Acha L., Tran S., Liu A., Patel R., Chennakesavalu M., Aneesh A., Huang C.C., Feinstein D.L., et al. Uptake and distribution of administered bone marrow mesenchymal stem cell extracellular vesicles in retina. Cells. 2021;10:730. doi: 10.3390/cells10040730.
    doi: 10.3390/cells10040730pmc: PMC8064505pubmed: 33806128google scholar: lookup
  45. Reddy S.K., Ballal A.R., Shailaja S., Seetharam R.N., Raghu C.H., Sankhe R., Pai K., Tender T., Mathew M., Aroor A., et al. Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy. Theranostics. 2023;13:2241–2255. doi: 10.7150/thno.78426.
    doi: 10.7150/thno.78426pmc: PMC10157735pubmed: 37153730google scholar: lookup
  46. Wang M., Yuan Q., Xie L. Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application. Stem Cells Int. 2018;2018:3057624. doi: 10.1155/2018/3057624.
    doi: 10.1155/2018/3057624pmc: PMC6022321pubmed: 30013600google scholar: lookup
  47. Chen Y., Yu Q., Hu Y., Shi Y. Current Research and Use of Mesenchymal Stem Cells in the Therapy of Autoimmune Diseases. Curr. Stem Cell Res. Ther. 2019;14:579–582. doi: 10.2174/1574888X14666190429141421.
  48. Gómez-Ferrer M., Amaro-Prellezo E., Dorronsoro A., Sánchez-Sánchez R., Vicente Á., Cosín-Roger J., Barrachina M.D., Baquero M.C., Valencia J., Sepúlveda P. HIF-Overexpression and Pro-Inflammatory Priming in Human Mesenchymal Stro-mal Cells Improves the Healing Properties of Extracellular Vesicles in Experimental Crohn’s Disease. Int. J. Mol. Sci. 2021;22:11269. doi: 10.3390/ijms222011269.
    doi: 10.3390/ijms222011269pmc: PMC8540690pubmed: 34681929google scholar: lookup
  49. Madel R.J., Börger V., Dittrich R., Bremer M., Tertel T., Phuong N.N.T., Baba H.A., Kordelas L., Staubach S., Stein F., et al. Independent human mesenchymal stromal cell-derived extracellular vesicle preparations differentially attenuate symptoms in an advanced murine graft-versus-host disease model. Cytotherapy. 2023;25:821–836. doi: 10.1016/j.jcyt.2023.03.008.
    doi: 10.1016/j.jcyt.2023.03.008pubmed: 37055321google scholar: lookup
  50. Hackel A., Vollmer S., Bruderek K., Lang S., Brandau S. Immunological priming of mesenchymal stromal/stem cells and their extracellular vesicles augments their therapeutic benefits in experimental graft-versus-host disease via engagement of PD-1 ligands. Front. Immunol. 2023;14:1078551. doi: 10.3389/fimmu.2023.1078551.
    doi: 10.3389/fimmu.2023.1078551pmc: PMC9978482pubmed: 36875112google scholar: lookup
  51. van Velthoven C.T., Braccioli L., Willemen H.L., Kavelaars A., Heijnen C.J. Therapeutic potential of genetically modified mesenchymal stem cells after neonatal hypoxic-ischemic brain damage. Mol. Ther. 2014;22:645–654. doi: 10.1038/mt.2013.260.
    doi: 10.1038/mt.2013.260pmc: PMC3944339pubmed: 24172866google scholar: lookup
  52. Mao Q., Nguyen P.D., Shanti R.M., Shi S., Shakoori P., Zhang Q., Le A.D. Gingiva-derived mesenchymal stem cell-extracellular vesicles activate schwann cell repair phenotype and promote nerve regeneration. Tissue Eng. Part A. 2019;25:887–900. doi: 10.1089/ten.tea.2018.0176.
    doi: 10.1089/ten.tea.2018.0176pubmed: 30311853google scholar: lookup
  53. Guy R., Herman S., Benyamini H., Ben-Zur T., Kobo H., Pasmanik-Chor M., Yaacobi D., Barel E., Yagil C., Yagil Y., et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles as Proposed Therapy in a Rat Model of Cerebral Small Vessel Disease. Int. J. Mol. Sci. 2022;23:11211. doi: 10.3390/ijms231911211.
    doi: 10.3390/ijms231911211pmc: PMC9569832pubmed: 36232513google scholar: lookup
  54. Yang Y., Yuan L., Cao H., Guo J., Zhou X., Zeng Z. Application and Molecular Mechanisms of Extracellular Vesicles De-rived from Mesenchymal Stem Cells in Osteoporosis. Curr. Issues Mol. Biol. 2022;44:6346–6367. doi: 10.3390/cimb44120433.
    doi: 10.3390/cimb44120433pmc: PMC9776574pubmed: 36547094google scholar: lookup
  55. Yin B., Ni J., Witherel C.E., Yang M., Burdick J.A., Wen C., Wong S.H.D. Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis theranostics. Theranostics. 2022;12:207–231. doi: 10.7150/thno.62708.
    doi: 10.7150/thno.62708pmc: PMC8690930pubmed: 34987642google scholar: lookup
  56. Zou J., Yang W., Cui W., Li C., Ma C., Ji X., Hong J., Qu Z., Chen J., Liu A., et al. Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing. J. Nanobiotechnol. 2023;21:14. doi: 10.1186/s12951-023-01778-6.
    doi: 10.1186/s12951-023-01778-6pmc: PMC9841717pubmed: 36642728google scholar: lookup
  57. Lötvall J., Hill A.F., Hochberg F., Buzás E.I., Di Vizio D., Gardiner C., Gho Y.S., Kurochkin I.V., Mathivanan S., Quesenberry P., et al. Minimal experimental requirements for definition of extracellular vesicles and their functions (MISEV2014): A position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles. 2014;3:26913. doi: 10.3402/jev.v3.26913.
    doi: 10.3402/jev.v3.26913pmc: PMC4275645pubmed: 25536934google scholar: lookup
  58. Moccia V., Sammarco A., Cavicchioli L., Castagnaro M., Bongiovanni L., Zappulli V. Extracellular Vesicles in Veterinary Medicine. Animals. 2022;12:2716. doi: 10.3390/ani12192716.
    doi: 10.3390/ani12192716pmc: PMC9559303pubmed: 36230457google scholar: lookup
  59. Arévalo-Turrubiarte M., Baratta M., Ponti G., Chiaradia E., Martignani E. Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro. Equine Vet. J. 2022;54:1133–1143. doi: 10.1111/evj.13537.
    doi: 10.1111/evj.13537pmc: PMC9787580pubmed: 34741769google scholar: lookup
  60. Navarrete F., Wong Y.S., Cabezas J., Riadi G., Manríquez J., Rojas D., Furlanetto Mancanares A.C., Rodriguez-Alvarez L., Saravia F., Castro F.O. Distinctive cellular transcriptomic signature and MicroRNA cargo of extracellular vesicles of horse adipose and endometrial mesenchymal stem cells from the same donors. Cell Reprogramming. 2020;22:311–327. doi: 10.1089/cell.2020.0026.
    doi: 10.1089/cell.2020.0026pubmed: 32991224google scholar: lookup
  61. Ji Y., Jiang W., Zeng F., Zou D., Li S., Zhang X., Zhu Q., Liang Q., Li M., Li D. Characterization of Canine Gingival-Derived Mesenchymal Stem Cells and Their Exosomes. J. Vet. Dent. 2023 doi: 10.1177/08987564231206459.
    doi: 10.1177/08987564231206459pubmed: 37844620google scholar: lookup
  62. Pipino C., Mandatori D., Buccella F., Lanuti P., Preziuso A., Castellani F., Grotta L., Di Tomo P., Marchetti S., Di Pietro N., et al. Identification and characterization of a stem cell-like population in bovine milk: A potential new source for regenerative medicine in veterinary. Stem Cells Dev. 2018;27:1587–1597. doi: 10.1089/scd.2018.0114.
    doi: 10.1089/scd.2018.0114pubmed: 30142991google scholar: lookup
  63. Eirin A., Riester S.M., Zhu X.Y., Tang H., Evans J.M., O’Brien D., van Wijnen A.J., Lerman L.O. MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells. Gene. 2014;551:55–64. doi: 10.1016/j.gene.2014.08.041.
    doi: 10.1016/j.gene.2014.08.041pmc: PMC4174680pubmed: 25158130google scholar: lookup
  64. Chen K.H., Chen C.H., Wallace C.G., Yuen C.M., Kao G.S., Chen Y.L., Shao P.L., Chen Y.L., Chai H.T., Lin K.C., et al. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget. 2016;7:74537. doi: 10.18632/oncotarget.12902.
    doi: 10.18632/oncotarget.12902pmc: PMC5342685pubmed: 27793019google scholar: lookup
  65. Eirin A., Zhu X.Y., Puranik A.S., Woollard J.R., Tang H., Dasari S., Lerman A., van Wijnen A.J., Lerman L.O. Comparative proteomic analysis of extracellular vesicles isolated from porcine adipose tissue-derived mesenchymal stem/stromal cells. Sci. Rep. 2016;6:36120. doi: 10.1038/srep36120.
    doi: 10.1038/srep36120pmc: PMC5081562pubmed: 27786293google scholar: lookup
  66. Eirin A., Zhu X.Y., Puranik A.S., Woollard J.R., Tang H., Dasari S., Lermna A., van Wijnen A.J., Lerman L.O. Comparative Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells. PLoS ONE. 2017;12:e0174303. doi: 10.1371/journal.pone.0174303.
  67. Eirin A., Zhu X.Y., Puranik A.S., Tang H., McGurren K.A., van Wijnen A.J., Lerman A., Lerman L.O. Mesenchymal stem cell–derived extracellular vesicles attenuate kidney inflammation. Kidney Int. 2017;92:114–124. doi: 10.1016/j.kint.2016.12.023.
    doi: 10.1016/j.kint.2016.12.023pmc: PMC5483390pubmed: 28242034google scholar: lookup
  68. Eirin A., Zhu X.Y., Jonnada S., Lerman A., van Wijnen A.J., Lerman L.O. Mesenchymal stem cell-derived extracellular vesicles improve the renal microvasculature in metabolic renovascular disease in swine. Cell Transplant. 2018;27:1080–1095. doi: 10.1177/0963689718780942.
    doi: 10.1177/0963689718780942pmc: PMC6158551pubmed: 29954220google scholar: lookup
  69. Meng Y., Eirin A., Zhu X.Y., O’Brien D.R., Lerman A., Van Wijnen A.J., Lerman L.O. The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells. Diabetol. Metab. Syndr. 2018;10:58. doi: 10.1186/s13098-018-0359-9.
    doi: 10.1186/s13098-018-0359-9pmc: PMC6054724pubmed: 30038668google scholar: lookup
  70. Khatri M., Richardson L.A., Meulia T. Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. Stem Cell Res. Ther. 2018;9:17. doi: 10.1186/s13287-018-0774-8.
    doi: 10.1186/s13287-018-0774-8pmc: PMC5789598pubmed: 29378639google scholar: lookup
  71. Meng Y., Eirin A., Zhu X.Y., Tang H., Chanana P., Lerman A., Van Wijnen A.J., Lerman L.O. The metabolic syndrome alters the miRNA signature of porcine adipose tissue-derived mesenchymal stem cells. Cytom. Part A. 2018;93:93–103. doi: 10.1002/cyto.a.23165.
    doi: 10.1002/cyto.a.23165pmc: PMC5756133pubmed: 28678424google scholar: lookup
  72. Eirin A., Zhu X.Y., Woollard J.R., Tang H., Dasari S., Lerman A., Lerman L.O. Metabolic syndrome interferes with packaging of proteins within porcine mesenchymal stem cell-derived extracellular vesicles. Stem Cells Transl. Med. 2019;8:430–440. doi: 10.1002/sctm.18-0171.
    doi: 10.1002/sctm.18-0171pmc: PMC6477000pubmed: 30707002google scholar: lookup
  73. Conley S.M., Shook J.E., Zhu X.Y., Eirin A., Jordan K.L., Woollard J.R., Isik B., Hickson L.J., Puranik A.S., Lerman L.O. Metabolic syndrome induces release of smaller extracellular vesicles from porcine mesenchymal stem cells. Cell Transplant. 2019;28:1271–1278. doi: 10.1177/0963689719860840.
    doi: 10.1177/0963689719860840pmc: PMC6767891pubmed: 31250656google scholar: lookup
  74. Thankam F.G., Chandra I., Diaz C., Dilisio M.F., Fleegel J., Gross R.M., Agrawal D.K. Matrix regeneration proteins in the hypoxia-triggered exosomes of shoulder tenocytes and adipose-derived mesenchymal stem cells. Mol. Cell Biochem. 2020;465:75–87. doi: 10.1007/s11010-019-03669-7.
    doi: 10.1007/s11010-019-03669-7pmc: PMC6957752pubmed: 31797254google scholar: lookup
  75. Zhang L., Zhu X.Y., Zhao Y., Eirin A., Liu L., Ferguson C.M., Tang H., Lerman A., Lerman L.O. Selective intrarenal delivery of mesenchymal stem cell-derived extracellular vesicles attenuates myocardial injury in experimental metabolic renovascular disease. Basic Res. Cardiol. 2020;115:16. doi: 10.1007/s00395-019-0772-8.
    doi: 10.1007/s00395-019-0772-8pmc: PMC7333936pubmed: 31938859google scholar: lookup
  76. Pawar A.S., Eirin A., Tang H., Zhu X.Y., Lerman A., Lerman L.O. Upregulated tumor necrosis factor-α transcriptome and proteome in adipose tissue-derived mesenchymal stem cells from pigs with metabolic syndrome. Cytokine. 2020;130:155080. doi: 10.1016/j.cyto.2020.155080.
    doi: 10.1016/j.cyto.2020.155080pmc: PMC7529712pubmed: 32240922google scholar: lookup
  77. Zhao Y., Zhu X., Zhang L., Ferguson C.M., Song T., Jiang K., Conley S.M., Krier J.D., Tang H., Saadiq I., et al. Mesenchymal stem/stromal cells and their extracellular vesicle progeny decrease injury in poststenotic swine kidney through different mechanisms. Stem Cells Dev. 2020;29:1190–1200. doi: 10.1089/scd.2020.0030.
    doi: 10.1089/scd.2020.0030pmc: PMC7482134pubmed: 32657229google scholar: lookup
  78. Song T., Eirin A., Zhu X., Zhao Y., Krier J.D., Tang H., Jordan K.L., Woollard J.R., Taner T., Lerman A., et al. Mesenchymal stem cell–derived extracellular vesicles induce regulatory t cells to ameliorate chronic kidney injury. Hypertension. 2020;75:1223–1232. doi: 10.1161/HYPERTENSIONAHA.119.14546.
  79. Li Y., Meng Y., Zhu X., Saadiq I.M., Jordan K.L., Eirin A., Lerman L.O. Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells. Cell Commun. Signal. 2020;18:124. doi: 10.1186/s12964-020-00624-8.
    doi: 10.1186/s12964-020-00624-8pmc: PMC7425605pubmed: 32787856google scholar: lookup
  80. Farahani R.A., Zhu X.Y., Tang H., Jordan K.L., Lerman A., Lerman L.O., Eirin A. Metabolic syndrome alters the cargo of mitochondria-related microRNAs in swine mesenchymal stem cell-derived extracellular vesicles, impairing their capacity to repair the stenotic kidney. Stem Cells Int. 2020;2020:8845635. doi: 10.1155/2020/8845635.
    doi: 10.1155/2020/8845635pmc: PMC7685840pubmed: 33281903google scholar: lookup
  81. Monguió-Tortajada M., Prat-Vidal C., Moron-Font M., Clos-Sansalvador M., Calle A., Gastelurrutia P., Cserkoova A., Morancho A., Ramírez M.A., Rosell A., et al. Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction. Bioact. Mater. 2021;6:3314–3327. doi: 10.1016/j.bioactmat.2021.02.026.
  82. Ferguson C.M., Farahani R.A., Zhu X.Y., Tang H., Jordan K.L., Saadiq I.M., Lerman A., Lerman L.O., Eirin A. Mesenchymal stem/stromal cell-derived extracellular vesicles elicit better preservation of the intra-renal microvasculature than renal revascularization in pigs with renovascular disease. Cells. 2021;10:763. doi: 10.3390/cells10040763.
    doi: 10.3390/cells10040763pmc: PMC8103265pubmed: 33807246google scholar: lookup
  83. Jiang Y., Hong S., Zhu X., Zhang L., Tang H., Jordan K.L., Saadiq I.M., Huang W., Lerman A., Eirin A., et al. IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension. Front. Immunol. 2022;13:940093. doi: 10.3389/fimmu.2022.940093.
    doi: 10.3389/fimmu.2022.940093pmc: PMC9530748pubmed: 36203611google scholar: lookup
  84. Monguió-Tortajada M., Prat-Vidal C., Martínez-Falguera D., Teis A., Soler-Botija C., Courageux Y., Munizaga-Larroudé M., Moron-Font M., Bayes-Genis A., Borràs F.E., et al. Acellular cardiac scaffolds enriched with MSC-derived extracellular vesicles limit ventricular remodelling and exert local and systemic immunomodulation in a myocardial infarction porcine model. Theranostics. 2022;12:4656. doi: 10.7150/thno.72289.
    doi: 10.7150/thno.72289pmc: PMC9254233pubmed: 35832072google scholar: lookup
  85. Jiang W., Cui Y., Li X., Xiong Y., Yue G., Yang Y. Isolation and Identification of Porcine Bone Marrow Mesenchymal Stem Cells and their Derived Extracellular Vesicles. JoVE. 2022;182:e63785. doi: 10.3791/63785.
    doi: 10.3791/63785pubmed: 35532274google scholar: lookup
  86. Hong S., Zhu X.Y., Jiang Y., Zhang L., Tang H., Jordan K.L., Saadiq I.M., Huang W., Lerman A., Eirin A., et al. Autologous Extracellular Vesicles attenuate cardiac injury in experimental atherosclerotic renovascular disease more effectively than their parent Mesenchymal Stem/Stromal Cells. Stem Cell Rev. Rep. 2023;19:700–712. doi: 10.1007/s12015-022-10473-2.
    doi: 10.1007/s12015-022-10473-2pmc: PMC10073252pubmed: 36344721google scholar: lookup
  87. Wang Y., Piao C., Liu T., Lu X., Ma Y., Zhang J., Liu G., Wang H. Effects of the exosomes of adipose-derived mesenchymal stem cells on apoptosis and pyroptosis of injured liver in miniature pigs. Biomed. Pharmacother. 2023;169:115873. doi: 10.1016/j.biopha.2023.115873.
    doi: 10.1016/j.biopha.2023.115873pubmed: 37979374google scholar: lookup
  88. Wang Y., Liu T., Jiao G., Lv Y., Piao C., Lu X., Ma H., Wang H. Exosomes from adipose-derived mesenchymal stem cells can attenuate liver injury caused by minimally invasive hemihepatectomy combined with ischemia-reperfusion in minipigs by modulating the endoplasmic reticulum stress response. Life Sci. 2023;321:121618. doi: 10.1016/j.lfs.2023.121618.
    doi: 10.1016/j.lfs.2023.121618pubmed: 36966916google scholar: lookup
  89. Shulman I., Ageeva T., Kostennikov A., Ogurcov S., Tazetdinova L., Kabdesh I., Rogozhin A., Ganiev I., Rizvanov I., Mukhamedshina Y. Intrathecal Injection of Autologous Mesenchymal Stem-Cell-Derived Extracellular Vesicles in Spinal Cord Injury: A Feasibility Study in Pigs. Int. J. Mol. Sci. 2023;24:8240. doi: 10.3390/ijms24098240.
    doi: 10.3390/ijms24098240pmc: PMC10179045pubmed: 37175946google scholar: lookup
  90. Aggarwal R., Shao A., Potel K.N., So S.W., Swingen C.M., Wright C.A., Hocum Stone L.L., McFalls E.O., Butterick T.A., Kelly R.F. Stem cell-derived exosome patch with coronary artery bypass graft restores cardiac function in chronically ischemic porcine myocardium. J. Thorac. Cardiovasc. Surg. 2023;166:e512–e530. doi: 10.1016/j.jtcvs.2023.07.014.
    doi: 10.1016/j.jtcvs.2023.07.014pubmed: 37482241google scholar: lookup
  91. Pascucci L., Alessandri G., Dall’Aglio C., Mercati F., Coliolo P., Bazzucchi C., Dante S., Petrini S., Curina G., Ceccarelli P. Membrane vesicles mediate pro-angiogenic activity of equine adipose-derived mesenchymal stromal cells. Vet. J. 2014;202:361–366. doi: 10.1016/j.tvjl.2014.08.021.
    doi: 10.1016/j.tvjl.2014.08.021pubmed: 25241947google scholar: lookup
  92. Pascucci L., Dall’Aglio C., Bazzucchi C., Mercati F., Mancini M.G., Pessina A., Alessandri G., Giammarioli M., Dante S., Brunati G., et al. Horse adipose-derived mesenchymal stromal cells constitutively produce membrane vesicles: A morphological study. Histol. Histopathol. 2015;30:549–557.
    pubmed: 25418078
  93. Marycz K., Michalak I., Kocherova I., Marędziak M., Weiss C. The Cladophora glomerata enriched by biosorption process in Cr (III) improves viability, and reduces oxidative stress and apoptosis in equine metabolic syndrome derived adipose mesenchymal stromal stem cells (ASCs) and their extracellular vesicles (MV’s) Mar. Drugs. 2017;15:385. doi: 10.3390/md15120385.
    doi: 10.3390/md15120385pmc: PMC5742845pubmed: 29292726google scholar: lookup
  94. Capomaccio S., Cappelli K., Bazzucchi C., Coletti M., Gialletti R., Moriconi F., Passamonti F., Pepe M., Petrini S., Mecocci S., et al. Equine adipose-derived mesenchymal stromal cells release extracellular vesicles enclosing different subsets of small RNAs. Stem Cells Int. 2019;2019:4957806. doi: 10.1155/2019/4957806.
    doi: 10.1155/2019/4957806pmc: PMC6442443pubmed: 31011332google scholar: lookup
  95. Klymiuk M.C., Balz N., Elashry M.I., Heimann M., Wenisch S., Arnhold S. Exosomes isolation and identification from equine mesenchymal stem cells. BMC Vet. Res. 2019;15:42. doi: 10.1186/s12917-019-1789-9.
    doi: 10.1186/s12917-019-1789-9pmc: PMC6348641pubmed: 30691449google scholar: lookup
  96. Kornicka-Garbowska K., Pędziwiatr R., Woźniak P., Kucharczyk K., Marycz K. Microvesicles isolated from 5-azacytidine-and-resveratrol-treated mesenchymal stem cells for the treatment of suspensory ligament injury in horse—A case report. Stem Cell Res. Ther. 2019;10:394. doi: 10.1186/s13287-019-1469-5.
    doi: 10.1186/s13287-019-1469-5pmc: PMC6921487pubmed: 31852535google scholar: lookup
  97. Hotham W.E., Thompson C., Szu-Ting L., Henson F.M.D. The anti-inflammatory effects of equine bone marrow stem cell-derived extracellular vesicles on autologous chondrocytes. Vet. Rec. 2021;8:e22. doi: 10.1002/vro2.22.
    doi: 10.1002/vro2.22pmc: PMC8580791pubmed: 34795904google scholar: lookup
  98. Mocchi M., Grolli S., Dotti S., Di Silvestre D., Villa R., Berni P., Conti V., Passignani G., Brambilla F., Del Bue M., et al. Equine mesenchymal stem/stromal cells freeze-dried secretome (Lyosecretome) for the treatment of musculoskeletal diseases: Production process validation and batch release test for clinical use. Pharmaceuticals. 2021;14:553. doi: 10.3390/ph14060553.
    doi: 10.3390/ph14060553pmc: PMC8226765pubmed: 34200627google scholar: lookup
  99. Contentin R., Jammes M., Bourdon B., Cassé F., Bianchi A., Audigié F., Branly T., Velot E., Galéra P. Bone marrow MSC secretome increases equine articular chondrocyte collagen accumulation and their migratory capacities. Int. J. Mol. Sci. 2022;23:5795. doi: 10.3390/ijms23105795.
    doi: 10.3390/ijms23105795pmc: PMC9146805pubmed: 35628604google scholar: lookup
  100. Soukup R., Gerner I., Gültekin S., Baik H., Oesterreicher J., Grillari J., Jenner F. Characterisation of extracellular vesicles from equine mesenchymal stem cells. Int. J. Mol. Sci. 2022;23:5858. doi: 10.3390/ijms23105858.
    doi: 10.3390/ijms23105858pmc: PMC9145091pubmed: 35628667google scholar: lookup
  101. Clarke E.J., Johnson E., Caamaño Gutierrez E., Andersen C., Berg L.C., Jenkins R.E., Lindegaard C., Uvebrant K., Lundgren-Åkerlund E., Turlo A., et al. Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis. Front. Vet. Sci. 2022;9:1057667. doi: 10.3389/fvets.2022.1057667.
    doi: 10.3389/fvets.2022.1057667pmc: PMC9730043pubmed: 36504839google scholar: lookup
  102. Soukup R., Gerner I., Mohr T., Gueltekin S., Grillari J., Jenner F. Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction. Int. J. Mol. Sci. 2023;24:10857. doi: 10.3390/ijms241310857.
    doi: 10.3390/ijms241310857pmc: PMC10342101pubmed: 37446034google scholar: lookup
  103. Abdelnaby E.A., Abdallah A.N., Anwar I.M., El-Tookhy O.S., Shamaa A.A. The therapeutic effect of stem cell-derived exosomes in the treatment of chronic endometritis as assessed by histopathological, Doppler and hormonal expression in Arabian mares. Equine Vet. Educ. 2023;36:347–356. doi: 10.1111/eve.13888.
    doi: 10.1111/eve.13888google scholar: lookup
  104. Cassé F., Velot E., Bianchi A., Audigié F., Contentin R., Galéra P. Pro-Inflammatory Cytokine Priming and Purification Method Modulate the Impact of Exosomes Derived from Equine Bone Marrow Mesenchymal Stromal Cells on Equine Articular Chondrocytes. Int. J. Mol. Sci. 2023;24:14169. doi: 10.3390/ijms241814169.
    doi: 10.3390/ijms241814169pmc: PMC10531906pubmed: 37762473google scholar: lookup
  105. El-Tookhy O.S., Shamaa A.A., Shehab G.G., Abdallah A.N., Azzam O.M. Histological evaluation of experimentally induced critical size defect skin wounds using exosomal solution of mesenchymal stem cells derived microvesicles. Int. J. Stem Cells. 2017;10:144–153. doi: 10.15283/ijsc17043.
    doi: 10.15283/ijsc17043pmc: PMC5741195pubmed: 29084422google scholar: lookup
  106. Qamar A.Y., Fang X., Kim M.J., Cho J. Improved post-thaw quality of canine semen after treatment with exosomes from conditioned medium of adipose-derived mesenchymal stem cells. Animals. 2019;9:865. doi: 10.3390/ani9110865.
    doi: 10.3390/ani9110865pmc: PMC6912283pubmed: 31731505google scholar: lookup
  107. Villatoro A.J., Alcoholado C., Martín-Astorga M.C., Fernández V., Cifuentes M., Becerra J. Comparative analysis and characterization of soluble factors and exosomes from cultured adipose tissue and bone marrow mesenchymal stem cells in canine species. Vet. Immunol. Immunopathol. 2019;208:6–15. doi: 10.1016/j.vetimm.2018.12.003.
    doi: 10.1016/j.vetimm.2018.12.003pubmed: 30712794google scholar: lookup
  108. An J.H., Li Q., Bhang D.H., Song W.J., Youn H.Y. TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis. Sci. Rep. 2020;10:2115. doi: 10.1038/s41598-020-58909-4.
    doi: 10.1038/s41598-020-58909-4pmc: PMC7005871pubmed: 32034203google scholar: lookup
  109. An J.H., Li Q., Ryu M.O., Nam A.R., Bhang D.H., Jung Y.C., Song W.J., Youn H.Y. TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis. PLoS ONE. 2020;15:e0220756. doi: 10.1371/journal.pone.0220756.
  110. Park S.M., An J.H., Lee J.H., Kim K.B., Chae H.K., Oh Y.I., Song W.J., Youn H.Y. Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase. PLoS ONE. 2021;16:e0254657. doi: 10.1371/journal.pone.0254657.
  111. Teshima T., Yuchi Y., Suzuki R., Matsumoto H., Koyama H. Immunomodulatory effects of canine adipose tissue mesenchymal stem cell-derived extracellular vesicles on stimulated CD4+ T cells isolated from peripheral blood mononuclear cells. J. Immunol. Res. 2021;2021:2993043. doi: 10.1155/2021/2993043.
    doi: 10.1155/2021/2993043pmc: PMC8384509pubmed: 34447855google scholar: lookup
  112. Mocchi M., Bari E., Dotti S., Villa R., Berni P., Conti V., Del Bue M., Squassino G.P., Segale L., Ramoni R., et al. Canine mesenchymal cell lyosecretome production and safety evaluation after allogenic intraarticular injection in osteoarthritic dogs. Animals. 2021;11:3271. doi: 10.3390/ani11113271.
    doi: 10.3390/ani11113271pmc: PMC8614457pubmed: 34828003google scholar: lookup
  113. Kuwahara Y., Yoshizaki K., Nishida H., Kamishina H., Maeda S., Takano K., Fujita N., Nishimura R., Jo J.I., Tabata Y., et al. Extracellular vesicles derived from canine mesenchymal stromal cells in serum free culture medium have anti-inflammatory effect on microglial cells. Front. Vet. Sci. 2021;8:633426. doi: 10.3389/fvets.2021.633426.
    doi: 10.3389/fvets.2021.633426pmc: PMC8113404pubmed: 33996963google scholar: lookup
  114. Kim S.Y., Yoon T.H., Na J., Yi S.J., Jin Y., Kim M., Oh T.H., Chung T.W. Mesenchymal stem cells and extracellular vesicles derived from canine adipose tissue ameliorates inflammation, skin barrier function and pruritus by reducing JAK/STAT signaling in atopic dermatitis. Int. J. Mol. Sci. 2022;23:4868. doi: 10.3390/ijms23094868.
    doi: 10.3390/ijms23094868pmc: PMC9101369pubmed: 35563259google scholar: lookup
  115. Cho B.S., Kim S.B., Kim S., Rhee B., Yoon J., Lee J.W. Canine Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Attenuate Atopic Dermatitis. Animals. 2023;13:2215. doi: 10.3390/ani13132215.
    doi: 10.3390/ani13132215pmc: PMC10339941pubmed: 37444013google scholar: lookup
  116. Liu H., Huang L., Chen F., Zhong Z., Ma X., Zhou Z., Cao S., Shen L., Peng G. Adipose-derived mesenchymal stem cells secrete extracellular vesicles: A potential cell-free therapy for canine renal ischaemia-reperfusion injury. Vet. Med. Sci. 2023;9:1134–1142. doi: 10.1002/vms3.1105.
    doi: 10.1002/vms3.1105pmc: PMC10188084pubmed: 36913179google scholar: lookup
  117. Yoshizaki K., Nishida H., Tabata Y., Jo J.I., Nakase I., Akiyoshi H. Controlled release of canine MSC-derived extracellular vesicles by cationized gelatin hydrogels. Regen. Ther. 2023;22:1–6. doi: 10.1016/j.reth.2022.11.009.
    doi: 10.1016/j.reth.2022.11.009pmc: PMC9761439pubmed: 36582604google scholar: lookup
  118. Sung S.E., Seo M.S., Kang K.K., Choi J.H., Lee S., Sung M., Kim K., Lee G.W., Lim J.H., Yang S.Y., et al. Mesenchymal stem cell exosomes derived from feline adipose tissue enhance the effects of anti-inflammation compared to fibroblasts-derived exosomes. Vet. Sci. 2021;8:182. doi: 10.3390/vetsci8090182.
    doi: 10.3390/vetsci8090182pmc: PMC8473240pubmed: 34564576google scholar: lookup
  119. Villatoro A.J., Martín-Astorga M.D.C., Alcoholado C., Cárdenas C., Fariñas F., Becerra J., Visser R. Altered proteomic profile of adipose tissue-derived mesenchymal stem cell exosomes from cats with severe chronic gingivostomatitis. Animals. 2021;11:2466. doi: 10.3390/ani11082466.
    doi: 10.3390/ani11082466pmc: PMC8388770pubmed: 34438923google scholar: lookup
  120. Villatoro A.J., Martín-Astorga M.D.C., Alcoholado C., Sánchez-Martín M.D.M., Becerra J. Proteomic analysis of the secretome and exosomes of feline adipose-derived mesenchymal stem cells. Animals. 2021;11:295. doi: 10.3390/ani11020295.
    doi: 10.3390/ani11020295pmc: PMC7912403pubmed: 33498940google scholar: lookup
  121. Li D., Luo H., Ruan H., Chen Z., Chen S., Wang B., Xie Y. Isolation and identification of exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells. BMC Vet. Res. 2021;17:272. doi: 10.1186/s12917-021-02960-4.
    doi: 10.1186/s12917-021-02960-4pmc: PMC8359027pubmed: 34384449google scholar: lookup
  122. Li W., Wang W., He X., Liao Z., Aierken A., Hua J., Wang Y., Lu D., Zhang S. Rapid recovery of male cats with postrenal acute kidney injury by treating with allogeneic adipose mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res. Ther. 2022;13:379. doi: 10.1186/s13287-022-03039-z.
    doi: 10.1186/s13287-022-03039-zpmc: PMC9331582pubmed: 35902973google scholar: lookup
  123. von Stade D., Meyers M., Johnson J., Schlegel T.T., Romeo A., Regan D., McGilvray K. Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes. Tissue Eng. Part A. 2023;29:282–291. doi: 10.1089/ten.tea.2022.0185.
    doi: 10.1089/ten.tea.2022.0185pmc: PMC10178933pubmed: 36792933google scholar: lookup
  124. De Coppiz P., Bartsch G.J., Siddiqui M.M., Xu T., Santos C.C., Perin L., Mostoslavsky G., Serre A.C., Snyder E.Y., Yoo J.J., et al. Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 2007;25:100–106. doi: 10.1038/nbt1274.
    doi: 10.1038/nbt1274pubmed: 17206138google scholar: lookup
  125. Delo D.M., De Coppi P., Bartsch G.J., Atala A. Amniotic fluid e placental stem cells. Methods Enzymol. 2006;419:426–438.
    pubmed: 17141065
  126. Gucciardo L., Lories R., Ochsenbein-Kolble N., Done E., Zwijsen A., Depresta J. Fetal mesenchymal stem cells: Isolation, properties e potential use in perinatology e regenerative medicine. BJOG. 2009;116:166–172. doi: 10.1111/j.1471-0528.2008.02005.x.
  127. In’t Anker P.S., Scherjon S.A., Kleijburg-van der Keur C., De Groot Swings G.M., Claas F.H., Fibbe W.E., Kanhai H.H.H. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells. 2004;22:1338–1345. doi: 10.1634/stemcells.2004-0058.
    doi: 10.1634/stemcells.2004-0058pubmed: 15579651google scholar: lookup
  128. Kern S., Eichler H., Stoeve J., Kluter H., Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24:1294–1301. doi: 10.1634/stemcells.2005-0342.
    doi: 10.1634/stemcells.2005-0342pubmed: 16410387google scholar: lookup
  129. Kögler G., Sensken S., Airey J.A., Trapp T., Mschen M., Feldhahn N., Liedtke S., Sorg R.V., Fischer J., Rosenbaum C., et al. New human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J. Exp. Med. 2004;200:123–135. doi: 10.1084/jem.20040440.
    doi: 10.1084/jem.20040440pmc: PMC2212008pubmed: 15263023google scholar: lookup
  130. Lange-Consiglio A., Rossi D., Tassan S., Perego R., Cremonesi F., Parolini O. Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: Immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo. Stem Cells Dev. 2013;22:3015–3024. doi: 10.1089/scd.2013.0214.
    doi: 10.1089/scd.2013.0214pubmed: 23795963google scholar: lookup
  131. Moore K.L., Persaud T.V.N. The developing human: Clinically oriented embryology. 1998, Sanders
  132. Evangelista M., Soncini M., Parolini O. Placenta-derived stem cells: New hope for cell therapy? Cytotechnology. 2008;58:33–42. doi: 10.1007/s10616-008-9162-z.
    doi: 10.1007/s10616-008-9162-zpmc: PMC2593758pubmed: 19002775google scholar: lookup
  133. Zucca E., Corsini E., Galbiati V., Lange-Consiglio A., Ferrucci F. Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: An in vitro approach to lung inflammation. Stem Cell Res. Ther. 2016;7:137. doi: 10.1186/s13287-016-0398-9.
    doi: 10.1186/s13287-016-0398-9pmc: PMC5028987pubmed: 27651133google scholar: lookup
  134. Perrini C., Strillacci M.G., Bagnato A., Esposti P., Marini M.G., Corradetti B., Bizzaro D., Idda A., Ledda S., Capra E., et al. Microvesicles secreted from equine amniotic-derived cells and their potential role in reducing inflammation in endometrial cells in an in-vitro model. Stem Cell Res. Ther. 2016;7:169. doi: 10.1186/s13287-016-0429-6.
    doi: 10.1186/s13287-016-0429-6pmc: PMC5114748pubmed: 27863532google scholar: lookup
  135. Lange-Consiglio A., Lazzari B., Perrini C., Pizzi F., Stella A., Cremonesi F., Capra E. MicroRNAs of equine amniotic mesenchymal cell-derived microvesicles and their involvement in anti-inflammatory processes. Cell Transplant. 2018;27:45–54. doi: 10.1177/0963689717724796.
    doi: 10.1177/0963689717724796pmc: PMC6434479pubmed: 29562776google scholar: lookup
  136. Lange-Consiglio A., Perrini C., Tasquier R., Deregibus M.C., Camussi G., Pascucci L., Marini M.G., Corradetti B., Bizzaro D., De Vita B., et al. Equine amniotic microvesicles and their anti-inflammatory potential in a tenocyte model in vitro. Stem Cells Dev. 2016;25:610–621. doi: 10.1089/scd.2015.0348.
    doi: 10.1089/scd.2015.0348pubmed: 26914245google scholar: lookup
  137. Desantis S., Accogli G., Albrizio M., Rossi R., Cremonesi F., Lange Consiglio A. Glycan profiling analysis of Equine amniotic progenitor mesenchymal cells and their derived extracellular microvesicles. Stem Cells Dev. 2019;28:812–821. doi: 10.1089/scd.2019.0013.
    doi: 10.1089/scd.2019.0013pubmed: 30900531google scholar: lookup
  138. Crain S.K., Robinson S.R., Thane K.E., Davis A.M., Meola D.M., Barton B.A., Yang V.K., Hoffman A.M. Extracellular vesicles from Wharton’s Jelly mesenchymal stem cells suppress CD4 expressing T Cells through Transforming Growth Factor Beta and Adenosine Signaling in a canine model. Stem Cells Dev. 2019;28:212–226. doi: 10.1089/scd.2018.0097.
    doi: 10.1089/scd.2018.0097pubmed: 30412034google scholar: lookup
  139. Wright A., Snyder O.L., He H., Christenson L.K., Fleming S., Weiss M.L. Procoagulant Activity of Umbilical Cord-Derived Mesenchymal Stromal Cells’ Extracellular Vesicles (MSC-EVs) Int. J. Mol. Sci. 2023;24:9216. doi: 10.3390/ijms24119216.
    doi: 10.3390/ijms24119216pmc: PMC10252357pubmed: 37298168google scholar: lookup
  140. Karam R.G., Motta L.C.B., de Almeida M.F., Bridi A., da Silveira J.C., Ambrósio C.E. Secretion pattern of canine amniotic stem cells derived extracellular vesicles. Anim. Reprod. 2022;19:e20220063. doi: 10.1590/1984-3143-ar2022-0063.
  141. Scassiotti R.F., de Paula Coutinho M., Pinto Santos S.I., Ferreira Pinto P.A., Ferreira de Almeida M., Karam R.G., da Silva Rosa P.M., Dos Santos Martins D., Coelho da Silveira J., Ambrósio C.E. Adipose and amnion-derived mesenchymal stem cells: Extracellular vesicles characterization and implication for reproductive biotechnology. Theriogenology. 2023;198:264–272. doi: 10.1016/j.theriogenology.2022.12.012.
  142. Pastore S., Troisi A., Romani R., Bellezza I., Gargaro M., De Michele A., Orlandi R., Guerrera G., Bazzano M., Polisca A. Isolation of extracellular vesicles from bitch’s amnion-derived cells culture and their CD59 expression: Preliminary results. Theriogenology. 2023;198:164–171. doi: 10.1016/j.theriogenology.2022.12.017.
  143. Ophelders D.R., Wolfs T.G., Jellema R.K., Zwanenburg A., Andriessen P., Delhaas T., Ludwig A.K., Radtke S., Peters V., Janssen L., et al. Mesenchymal stromal cell-derived extracellular vesicles protect the fetal brain after hypoxia-ischemia. Stem Cells Transl. Med. 2016;5:754–763. doi: 10.5966/sctm.2015-0197.
    doi: 10.5966/sctm.2015-0197pmc: PMC4878333pubmed: 27160705google scholar: lookup
  144. Jenner F., Wagner A., Gerner I., Ludewig E., Trujanovic R., Rohde E., von Rechenberg B., Gimona M., Traweger A. Evaluation of the potential of umbilical cord mesenchymal stromal cell–derived small extracellular vesicles to improve rotator cuff healing: A pilot ovine study. Am. J. Sports Med. 2023;51:331–342. doi: 10.1177/03635465221145958.
    doi: 10.1177/03635465221145958pubmed: 36645050google scholar: lookup
  145. Homma K., Bazhanov N., Hashimoto K., Shimizu M., Heathman T., Hao Q., Nawgiri R., Muthukumarana V., Lee J.W., Prough D.S., et al. Mesenchymal stem cell-derived exosomes for treatment of sepsis. Front. Immunol. 2023;14:1136964. doi: 10.3389/fimmu.2023.1136964.
    doi: 10.3389/fimmu.2023.1136964pmc: PMC10169690pubmed: 37180159google scholar: lookup
  146. Lange-Consiglio A., Lazzari B., Pizzi F., Idda A., Cremonesi F., Capra E. Amniotic microvesicles impact hatching and pregnancy percentages of in vitro bovine embryos and blastocyst microRNA expression versus in vivo controls. Sci. Rep. 2020;10:501. doi: 10.1038/s41598-019-57060-z.
    doi: 10.1038/s41598-019-57060-zpmc: PMC6965648pubmed: 31949175google scholar: lookup
  147. Lange-Consiglio A., Gusmara C., Manfredi E., Idda A., Soggiu A., Greco V., Bonizzi L., Cremonesi F., Zecconi A. Antimicrobial effects of conditioned medium from amniotic progenitor cells in vitro and in vivo: Toward tissue regenerative therapies for bovine mastitis. Front. Vet. Sci. 2019;6:443. doi: 10.3389/fvets.2019.00443.
    doi: 10.3389/fvets.2019.00443pmc: PMC6930869pubmed: 31921904google scholar: lookup
  148. Lange-Consiglio A., Funghi F., Cantile C., Idda A., Cremonesi F., Riccaboni P. Case report: Use of amniotic microvesicles for regenerative medicine treatment of a mare with chronic endometritis. Front. Vet. Sci. 2020;7:347. doi: 10.3389/fvets.2020.00347.
    doi: 10.3389/fvets.2020.00347pmc: PMC7311574pubmed: 32626730google scholar: lookup
  149. Lange-Consiglio A., Gaspari G., Funghi F., Capra E., Cretich M., Frigerio R., Bosi G., Cremonesi F. Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis. Int. J. Mol. Sci. 2023;24:5166. doi: 10.3390/ijms24065166.
    doi: 10.3390/ijms24065166pmc: PMC10049450pubmed: 36982240google scholar: lookup
  150. Mocchi M., Bari E., Marrubini G., Bonda A.F., Perteghella S., Tartara F., Cofano F., di Perna G., Giovannelli L., Mandracchia D., et al. Freeze-Dried Mesenchymal Stem Cell-Secretome pharmaceuticalization: Optimization of formulation and manufacturing process robustness. Pharmaceutics. 2021;13:1129. doi: 10.3390/pharmaceutics13081129.
  151. Bemis L.T., McCue P.M., Hatzel J.N., Bemis J., Ferris R.A. Evidence for production of early pregnancy factor (Hsp10), micro RNAs and exosomes by day 8 equine embryos. 8th ISEET Abstracts. J. Equine Vet. Sci. 2012;32:398. doi: 10.1016/j.jevs.2012.05.010.
  152. Ng Y.H., Rome S., Jalabert A., Forterre A., Singh H., Hincks C.L., Salamonsen L.A. Endometrial exosomes/microvesicles in the uterine microenvironment: A new paradigm for embryo-endometrial cross talk at implantation. PLoS ONE. 2013;8:e58502. doi: 10.1371/journal.pone.0058502.
  153. Rebordao M.R., Amaral A., Lukasik K., Szostek-Mioduchowska A., Pinto-Bravo P., Galvao A., Skarzynski D.J., Ferreira-Dias G. Impairment of the antifi-brotic prostaglandin E2 pathway may influence neutrophil extracellular trapsinduced fibrosis in the mare endometrium. Domest. Anim. Endocrinol. 2019;67:1–10. doi: 10.1016/j.domaniend.2018.10.004.
  154. Volk S.W., Bohling M.W. Comparative wound healing--are the small animal veterinarian’s clinical patients an improved translational model for human wound healing research? Wound Repair Regen. 2013;21:372–381. doi: 10.1111/wrr.12049.
    doi: 10.1111/wrr.12049pubmed: 23627643google scholar: lookup
  155. Iacono E., Lanci A., Merlo B., Ricci F., Pirrone A., Antonelli C., Mariella J., Castagnetti C. Effects of amniotic fluid mesenchymal stem cells in carboxymethyl cellulosegel on healing of spontaneous pressure sores: Clinical outcome in seven hospitalized neonatal foals. Turk. J. Biol. 2016;40:484–492. doi: 10.3906/biy-1507-147.
    doi: 10.3906/biy-1507-147google scholar: lookup
  156. Lanci A., Merlo B., Mariella J., Castagnetti C., Iacono E. Heterologous Wharton’s jelly derived mesenchymal stem cells application on a large chronic skin wound in a 6-month-old filly. Front. Vet. Sci. 2019;6:9. doi: 10.3389/fvets.2019.00009.
    doi: 10.3389/fvets.2019.00009pmc: PMC6363668pubmed: 30761313google scholar: lookup
  157. Enciso N., Avedillo L., Fermín M.L., Fragío C., Tejero C. Cutaneous wound healing: Canine allogeneic ASC therapy. Stem Cell Res. Ther. 2020;11:261. doi: 10.1186/s13287-020-01778-5.
    doi: 10.1186/s13287-020-01778-5pmc: PMC7325024pubmed: 32600465google scholar: lookup
  158. Cheng Y., Cao X., Qin L. Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy for Sepsis. Front. Immunol. 2020;11:647. doi: 10.3389/fimmu.2020.00647.
    doi: 10.3389/fimmu.2020.00647pmc: PMC7186296pubmed: 32373121google scholar: lookup
  159. Manzoor T., Saleem A., Farooq N., Dar L.A., Nazir J., Saleem S., Ismail S., Gugjoo M.B., Shiekh P.A., Ahmad S.M. Extracellular vesicles derived from mesenchymal stem cells—A novel therapeutic tool in infectious diseases. Inflamm. Regen. 2023;43:17. doi: 10.1186/s41232-023-00266-6.
    doi: 10.1186/s41232-023-00266-6pmc: PMC9970864pubmed: 36849892google scholar: lookup
  160. Palma E., Tilocca B., Roncada P. Antimicrobial resistance in veterinary medicine: An overview. Int. J. Mol. Sci. 2020;21:1914. doi: 10.3390/ijms21061914.
    doi: 10.3390/ijms21061914pmc: PMC7139321pubmed: 32168903google scholar: lookup
  161. Indira V., Corteling R., Stevanato L., Hicks C., Sinden J. The development of stem cell-derived exosomes as a cell-free regenerative medicine. J. Circ. Biomark. 2014;3:2
  162. Pollock K., Stroemer P., Patel S., Stevanato L., Hope A., Miljan E., Dong Z., Hodges H., Price J., Sinden J.D. A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke. Exp. Neurol. 2006;199:143–155. doi: 10.1016/j.expneurol.2005.12.011.
  163. Yeo R.W., Lai R.C., Zhang B., Tan S.S., Yin Y., Teh B.J., Lim S.K. Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery. Adv. Drug Deliv. Rev. 2013;65:336–341. doi: 10.1016/j.addr.2012.07.001.
    doi: 10.1016/j.addr.2012.07.001pubmed: 22780955google scholar: lookup
  164. Haraszti R.A., Miller R., Stoppato M., Sere Y.Y., Coles A., Didiot M.C., Wollacott R., Sapp E., Dubuke M.L., Li X., et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol. Ther. 2018;26:2838–2847. doi: 10.1016/j.ymthe.2018.09.015.
    doi: 10.1016/j.ymthe.2018.09.015pmc: PMC6277553pubmed: 30341012google scholar: lookup
  165. Nordin J.Z., Lee Y., Vader P., Mager I., Johansson H.J., Heusermann W., Wiklander O.P.B., Hällbrink M., Seow Y., Bultema J.J., et al. Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. Nanomedicine. 2015;11:879–883. doi: 10.1016/j.nano.2015.01.003.
    doi: 10.1016/j.nano.2015.01.003pubmed: 25659648google scholar: lookup
  166. Benedikter B.J., Bouwman F.G., Vajen T., Heinzmann A.C.A., Grauls G., Mariman E.C., Wouters E.F.M., Savelkoul P.H., Lopez-Iglesias C., Koenen R.R., et al. Ultrafiltration combined with size exclusion chromatography efficiently isolates extracellular vesicles from cell culture media for compositional and functional studies. Sci. Rep. 2017;7:15297. doi: 10.1038/s41598-017-15717-7.
    doi: 10.1038/s41598-017-15717-7pmc: PMC5681555pubmed: 29127410google scholar: lookup
  167. Mol E.A., Goumans M.J., Doevendans P.A., Sluijter J.P.G., Vader P. Higher functionality of extracellular vesicles isolated using sizeexclusion chromatography compared to ultracentrifugation. Nanomedicine. 2017;13:2061–2065. doi: 10.1016/j.nano.2017.03.011.
    doi: 10.1016/j.nano.2017.03.011pubmed: 28365418google scholar: lookup
  168. Monguio-Tortajada M., Galvez-Monton C., Bayes-Genis A., Roura S., Borras F.E. Extracellular vesicle isolation methods: Rising impact of size-exclusion chromatography. Cell Mol. Life Sci. 2019;76:2369–2382. doi: 10.1007/s00018-019-03071-y.
    doi: 10.1007/s00018-019-03071-ypmc: PMC11105396pubmed: 30891621google scholar: lookup
  169. Lener T., Gimona M., Aigner L., Börger V., Buzas E., Camussi G., Chaput N., Chatterjee D., Court F.A., Del Portillo H.A., et al. Applying extracellular vesicles based therapeutics in clinical trials—An ISEV position paper. J. Extracell. Vesicles. 2015;4:30087. doi: 10.3402/jev.v4.30087.
    doi: 10.3402/jev.v4.30087pmc: PMC4698466pubmed: 26725829google scholar: lookup
  170. Pachler K., Lener T., Streif D., Dunai Z.A., Desgeorges A., Feichtner M., Öller M., Schallmoser K., Rohde E., Gimona M. A good manufacturing prac-tice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy. 2017;19:458–472. doi: 10.1016/j.jcyt.2017.01.001.
    doi: 10.1016/j.jcyt.2017.01.001pubmed: 28188071google scholar: lookup
  171. Burrello J., Monticone S., Gai C., Gomez Y., Kholia S., Camussi G. Stem cell-derived extracellular vesicles and immune-modulation. Front. Cell Dev. Biol. 2016;4:83. doi: 10.3389/fcell.2016.00083.
    doi: 10.3389/fcell.2016.00083pmc: PMC4992732pubmed: 27597941google scholar: lookup

Citations

This article has been cited 5 times.
  1. González E, Falcón-Pérez JM. Expanding Horizons: Next-Generation and Interdisciplinary Advances in the Applications of Extracellular Vesicles.. J Extracell Biol 2025 Dec;4(12):e70101.
    doi: 10.1002/jex2.70101pubmed: 41404187google scholar: lookup
  2. Gad WA, Ibrahim S, Nagdy H, Elsawy BSM, Aboelsoued D, Abdel-Ghany HSM, Abdel-Wareth AAA, Abd El-Razik KA, Mahmoud KGM, Soliman WTM, Taqi MO. Bridging biology and therapy: translational advances of extracellular vesicles in veterinary clinical practice.. Vet Res Commun 2025 Nov 17;50(1):42.
    doi: 10.1007/s11259-025-10917-3pubmed: 41247562google scholar: lookup
  3. Prabowo TA, Muttaqin Z, Herdis H, Santoso S, Priyatno TP, Sitaresmi PI, Kostaman T, Hudaya MF, Asmarasari SA, Kusumaningrum DA, Azizah N, Suyatno S. Mesenchymal stem cell therapy in bovine reproduction: Mechanistic insights, clinical applications, and translational challenges.. Vet World 2025 Sep;18(9):2888-2899.
  4. Aeri A, Gorla M, Sharma GT. Veterinary Regenerative Medicine: The Evolving Role of Stem Cell-Based Therapies.. Stem Cell Rev Rep 2025 Nov;21(8):2484-2510.
    doi: 10.1007/s12015-025-10963-zpubmed: 40900287google scholar: lookup
  5. Oontawee S, Siriarchavatana P, Rodprasert W, Padeta I, Pamulang YV, Somparn P, Pisitkun T, Nambooppha B, Sthitmatee N, Na Nan D, Osathanon T, Egusa H, Sawangmake C. Small extracellular vesicles derived from sequential stimulation of canine adipose-derived mesenchymal stem cells enhance anti-inflammatory activity.. BMC Vet Res 2025 Jan 21;21(1):31.
    doi: 10.1186/s12917-024-04465-2pubmed: 39838398google scholar: lookup