Stem cells and development2016; 25(8); 610-621; doi: 10.1089/scd.2015.0348

Equine Amniotic Microvesicles and Their Anti-Inflammatory Potential in a Tenocyte Model In Vitro.

Abstract: Administration of horse amniotic mesenchymal cells (AMCs) and their conditioned medium (AMC-CM) improves the in vivo recovery of spontaneous equine tendon lesions and inhibits in vitro proliferation of peripheral blood mononuclear cells (PBMC). This process may involve microvesicles (MVs) as an integral component of cell-to-cell communication during tissue regeneration. In this study, the presence and type of MVs secreted by AMCs were investigated and the response of equine tendon cells to MVs was studied using a dose-response curve at different concentrations and times. Moreover, the ability of MVs to counteract in vitro inflammation of tendon cells induced by lipopolysaccharide was studied through the expression of some proinflammatory genes such as metallopeptidase (MPP) 1, 9, and 13 and tumor necrosis factor-α (TNFα), and expression of transforming growth factor-β (TGF-β). Lastly, the immunomodulatory potential of MVs was investigated. Results show that AMCs secrete MVs ranging in size from 100 to 200 nm. An inverse relationship between concentration and time was found in their uptake by tendon cells: the maximal uptake occurred after 72 h at a concentration of 40 × 10(6) MVs/mL. MVs induced a downregulation of MMP1, MMP9, MMP13, and TNFα expression without affecting PBMC proliferation, contrary to CM and supernatant. Our data suggest that MVs contribute to in vivo healing of tendon lesions, alongside soluble factors in AMC-CM.
Publication Date: 2016-02-26 PubMed ID: 26914245DOI: 10.1089/scd.2015.0348Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study explores the effect of microvesicles (MVs) – tiny vesicles released by cells – secreted by horse amniotic mesenchymal cells (AMCs) on equine tendon inflammation and its role in the repair process, highlighting its potential to reduce inflammation and thus enhance tendon healing in horses.

Investigation into Microvesicles

  • The researchers looked into the presence and types of microvesicles (MVs) produced by amniotic mesenchymal cells (AMCs). These AMCs have previously been determined to aid the healing of spontaneous equine tendon injuries, and inhibit the proliferation of peripheral blood mononuclear cells (PBMC) when used in their conditioned medium (AMC-CM).

Equine Tendon Cells’ Response to MVs

  • The study also investigated how equine tendon cells responded to MVs. A dose-response curve was utilized in order to ascertain the effects at different concentrations and time intervals.
  • Microvesicles were found to have an inverse relationship between concentration and time in their uptake by tendon cells, with the highest uptake occurring after 72 hours at a concentration of 40 × 10(6) MVs/mL.

Anti-Inflammatory Effect of MVs

  • The research further studied the ability of MVs to counteract tendon cell inflammation that was artificially induced. Specifically, they looked at expression levels of several pro-inflammatory genes (MPP1, 9, 13 and tumor necrosis factor-α (TNFα)) and of the anti-inflammatory gene transforming growth factor-β (TGF-β). The MVs were found to decrease the expression of the pro-inflammatory genes, demonstrating their anti-inflammatory potential.

Immunomodulatory Potential of MVs

  • The study also probed the immunomodulatory potential of MVs, finding that while the MVs could decrease expression of pro-inflammatory genes, they did not affect the proliferation of PBMCs. This is contrary to the effects of the conditioned medium (CM) and its supernatant, suggesting that the anti-inflammatory effects of CM are not solely due to the presence of MVs.
  • However, the results do suggest that MVs play a significant role in aiding the healing of tendon lesions, along with the soluble factors in AMC-CM.

Cite This Article

APA
Lange-Consiglio A, Perrini C, Tasquier R, Deregibus MC, Camussi G, Pascucci L, Marini MG, Corradetti B, Bizzaro D, De Vita B, Romele P, Parolini O, Cremonesi F. (2016). Equine Amniotic Microvesicles and Their Anti-Inflammatory Potential in a Tenocyte Model In Vitro. Stem Cells Dev, 25(8), 610-621. https://doi.org/10.1089/scd.2015.0348

Publication

ISSN: 1557-8534
NlmUniqueID: 101197107
Country: United States
Language: English
Volume: 25
Issue: 8
Pages: 610-621

Researcher Affiliations

Lange-Consiglio, Anna
  • 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
Perrini, Claudia
  • 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
Tasquier, Riccardo
  • 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
Deregibus, Maria Chiara
  • 2 Department of Internal Medicine and Molecular Biotechnology Center, University of Torino , Torino, Italy .
Camussi, Giovanni
  • 2 Department of Internal Medicine and Molecular Biotechnology Center, University of Torino , Torino, Italy .
Pascucci, Luisa
  • 3 Department of Veterinary Medicine, University of Perugia , Perugia, Italy .
Marini, Maria Giovanna
  • 4 Biochemistry, Biology and Genetics, Universitu00e0 Politecnica delle Marche , Ancona, Italy .
Corradetti, Bruna
  • 4 Biochemistry, Biology and Genetics, Universitu00e0 Politecnica delle Marche , Ancona, Italy .
Bizzaro, Davide
  • 4 Biochemistry, Biology and Genetics, Universitu00e0 Politecnica delle Marche , Ancona, Italy .
De Vita, Bruna
  • 5 Department of Animal Reproduction and Radiology, FMVZ, UNESP , Botucatu, San Paolo, Brazil .
Romele, Pietro
  • 6 Centro di Ricerca E. Menni, Fondazione Poliambulanza, Istituto Ospedaliero , Brescia, Italy .
Parolini, Ornella
  • 6 Centro di Ricerca E. Menni, Fondazione Poliambulanza, Istituto Ospedaliero , Brescia, Italy .
Cremonesi, Fausto
  • 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
  • 7 Department of Veterinary Medical Science, Universitu00e0 degli Studi di Milano , Milano, Italy .

MeSH Terms

  • Amnion / cytology
  • Animals
  • Cell Proliferation
  • Cell-Derived Microparticles / physiology
  • Cells, Cultured
  • Collagenases / metabolism
  • Culture Media, Conditioned
  • Horses
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / pharmacology
  • Mesenchymal Stem Cells / metabolism
  • Tendons / cytology
  • Tenocytes / immunology
  • Tenocytes / metabolism

Citations

This article has been cited 28 times.
  1. 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 Jun 29;24(13).
    doi: 10.3390/ijms241310857pubmed: 37446034google scholar: lookup
  2. 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 Mar 8;24(6).
    doi: 10.3390/ijms24065166pubmed: 36982240google scholar: lookup
  3. Ning C, Li P, Gao C, Fu L, Liao Z, Tian G, Yin H, Li M, Sui X, Yuan Z, Liu S, Guo Q. Recent advances in tendon tissue engineering strategy.. Front Bioeng Biotechnol 2023;11:1115312.
    doi: 10.3389/fbioe.2023.1115312pubmed: 36890920google scholar: lookup
  4. Quintero D, Perucca Orfei C, Kaplan LD, de Girolamo L, Best TM, Kouroupis D. The roles and therapeutic potentialof mesenchymal stem/stromal cells and their extracellular vesicles in tendinopathies.. Front Bioeng Biotechnol 2023;11:1040762.
    doi: 10.3389/fbioe.2023.1040762pubmed: 36741745google scholar: lookup
  5. Papait A, Ragni E, Cargnoni A, Vertua E, Romele P, Masserdotti A, Perucca Orfei C, Signoroni PB, Magatti M, Silini AR, De Girolamo L, Parolini O. Comparison of EV-free fraction, EVs, and total secretome of amniotic mesenchymal stromal cells for their immunomodulatory potential: a translational perspective.. Front Immunol 2022;13:960909.
    doi: 10.3389/fimmu.2022.960909pubmed: 36052081google scholar: lookup
  6. Soukup R, Gerner I, Gu00fcltekin S, Baik H, Oesterreicher J, Grillari J, Jenner F. Characterisation of Extracellular Vesicles from Equine Mesenchymal Stem Cells.. Int J Mol Sci 2022 May 23;23(10).
    doi: 10.3390/ijms23105858pubmed: 35628667google scholar: lookup
  7. Russo V, El Khatib M, Prencipe G, Citeroni MR, Faydaver M, Mauro A, Berardinelli P, Cerveru00f3-Varona A, Haidar-Montes AA, Turriani M, Di Giacinto O, Raspa M, Scavizzi F, Bonaventura F, Stu00f6ckl J, Barboni B. Tendon Immune Regeneration: Insights on the Synergetic Role of Stem and Immune Cells during Tendon Regeneration.. Cells 2022 Jan 27;11(3).
    doi: 10.3390/cells11030434pubmed: 35159244google scholar: lookup
  8. Lange-Consiglio A, Capra E, Herrera V, Lang-Olip I, Ponsaerts P, Cremonesi F. Application of Perinatal Derivatives in Ovarian Diseases.. Front Bioeng Biotechnol 2022;10:811875.
    doi: 10.3389/fbioe.2022.811875pubmed: 35141212google scholar: lookup
  9. Hotham WE, Thompson C, Szu-Ting L, Henson FMD. The anti-inflammatory effects of equine bone marrow stem cell-derived extracellular vesicles on autologous chondrocytes.. Vet Rec Open 2021 Dec;8(1):e22.
    doi: 10.1002/vro2.22pubmed: 34795904google scholar: lookup
  10. Meeremans M, Van Damme L, De Spiegelaere W, Van Vlierberghe S, De Schauwer C. Equine Tenocyte Seeding on Gelatin Hydrogels Improves Elongated Morphology.. Polymers (Basel) 2021 Feb 28;13(5).
    doi: 10.3390/polym13050747pubmed: 33670848google scholar: lookup
  11. Ragni E, Papait A, Perucca Orfei C, Silini AR, Colombini A, Viganu00f2 M, Libonati F, Parolini O, de Girolamo L. Amniotic membrane-mesenchymal stromal cells secreted factors and extracellular vesicle-miRNAs: Anti-inflammatory and regenerative features for musculoskeletal tissues.. Stem Cells Transl Med 2021 Jul;10(7):1044-1062.
    doi: 10.1002/sctm.20-0390pubmed: 33656805google scholar: lookup
  12. Jafari A, Rezaei-Tavirani M, Farhadihosseinabadi B, Zali H, Niknejad H. Human amniotic mesenchymal stem cells to promote/suppress cancer: two sides of the same coin.. Stem Cell Res Ther 2021 Feb 12;12(1):126.
    doi: 10.1186/s13287-021-02196-xpubmed: 33579346google scholar: lookup
  13. Zakirova EY, Aimaletdinov AM, Malanyeva AG, Rutland CS, Rizvanov AA. Extracellular Vesicles: New Perspectives of Regenerative and Reproductive Veterinary Medicine.. Front Vet Sci 2020;7:594044.
    doi: 10.3389/fvets.2020.594044pubmed: 33330719google scholar: lookup
  14. Lui PPY. Mesenchymal Stem Cell-Derived Extracellular Vesicles for the Promotion of Tendon Repair - an Update of Literature.. Stem Cell Rev Rep 2021 Apr;17(2):379-389.
    doi: 10.1007/s12015-020-10023-8pubmed: 32785869google scholar: lookup
  15. 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.2020.00347pubmed: 32626730google scholar: lookup
  16. Ragni E, Perucca Orfei C, Silini AR, Colombini A, Viganu00f2 M, Parolini O, de Girolamo L. miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells.. Pharmaceutics 2020 Apr 11;12(4).
    doi: 10.3390/pharmaceutics12040347pubmed: 32290510google scholar: lookup
  17. 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.2019.00443pubmed: 31921904google scholar: lookup
  18. Lim WL, Liau LL, Ng MH, Chowdhury SR, Law JX. Current Progress in Tendon and Ligament Tissue Engineering.. Tissue Eng Regen Med 2019 Dec;16(6):549-571.
    doi: 10.1007/s13770-019-00196-wpubmed: 31824819google scholar: lookup
  19. Capomaccio S, Cappelli K, Bazzucchi C, Coletti M, Gialletti R, Moriconi F, Passamonti F, Pepe M, Petrini S, Mecocci S, Silvestrelli M, Pascucci L. Equine Adipose-Derived Mesenchymal Stromal Cells Release Extracellular Vesicles Enclosing Different Subsets of Small RNAs.. Stem Cells Int 2019;2019:4957806.
    doi: 10.1155/2019/4957806pubmed: 31011332google scholar: lookup
  20. Iacono E, Pascucci L, Bazzucchi C, Cunto M, Ricci F, Rossi B, Merlo B. Could hypoxia influence basic biological properties and ultrastructural features of adult canine mesenchymal stem /stromal cells?. Vet Res Commun 2018 Dec;42(4):297-308.
    doi: 10.1007/s11259-018-9738-9pubmed: 30238341google scholar: lookup
  21. Giulietti M, Santoni M, Cimadamore A, Carrozza F, Piva F, Cheng L, Lopez-Beltran A, Scarpelli M, Battelli N, Montironi R. Exploring Small Extracellular Vesicles for Precision Medicine in Prostate Cancer.. Front Oncol 2018;8:221.
    doi: 10.3389/fonc.2018.00221pubmed: 29951374google scholar: lookup
  22. 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 Jan;27(1):45-54.
    doi: 10.1177/0963689717724796pubmed: 29562776google scholar: lookup
  23. Corradetti B, Taraballi F, Giretti I, Bauza G, Pistillo RS, Banche Niclot F, Pandolfi L, Demarchi D, Tasciotti E. Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes.. Front Bioeng Biotechnol 2017;5:54.
    doi: 10.3389/fbioe.2017.00054pubmed: 28983481google scholar: lookup
  24. Corradetti B, Taraballi F, Martinez JO, Minardi S, Basu N, Bauza G, Evangelopoulos M, Powell S, Corbo C, Tasciotti E. Hyaluronic acid coatings as a simple and efficient approach to improve MSC homing toward the site of inflammation.. Sci Rep 2017 Aug 11;7(1):7991.
    doi: 10.1038/s41598-017-08687-3pubmed: 28801676google scholar: lookup
  25. Balbi C, Piccoli M, Barile L, Papait A, Armirotti A, Principi E, Reverberi D, Pascucci L, Becherini P, Varesio L, Mogni M, Coviello D, Bandiera T, Pozzobon M, Cancedda R, Bollini S. First Characterization of Human Amniotic Fluid Stem Cell Extracellular Vesicles as a Powerful Paracrine Tool Endowed with Regenerative Potential.. Stem Cells Transl Med 2017 May;6(5):1340-1355.
    doi: 10.1002/sctm.16-0297pubmed: 28271621google scholar: lookup
  26. Perrini C, Strillacci MG, Bagnato A, Esposti P, Marini MG, Corradetti B, Bizzaro D, Idda A, Ledda S, Capra E, Pizzi F, Lange-Consiglio A, Cremonesi F. 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 Nov 18;7(1):169.
    doi: 10.1186/s13287-016-0429-6pubmed: 27863532google scholar: lookup
  27. 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 Sep 20;7(1):137.
    doi: 10.1186/s13287-016-0398-9pubmed: 27651133google scholar: lookup
  28. Di Germanio C, Bernier M, Petr M, Mattioli M, Barboni B, de Cabo R. Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence.. Oncotarget 2016 Jun 28;7(26):39051-39064.
    doi: 10.18632/oncotarget.9694pubmed: 27259996google scholar: lookup