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 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
- 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
Researcher Affiliations
- 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
- 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
- 1 Large Animal Hospital, Reproduction Unit, Universitu00e0 degli Studi di Milano , Lodi, Italy .
- 2 Department of Internal Medicine and Molecular Biotechnology Center, University of Torino , Torino, Italy .
- 2 Department of Internal Medicine and Molecular Biotechnology Center, University of Torino , Torino, Italy .
- 3 Department of Veterinary Medicine, University of Perugia , Perugia, Italy .
- 4 Biochemistry, Biology and Genetics, Universitu00e0 Politecnica delle Marche , Ancona, Italy .
- 4 Biochemistry, Biology and Genetics, Universitu00e0 Politecnica delle Marche , Ancona, Italy .
- 4 Biochemistry, Biology and Genetics, Universitu00e0 Politecnica delle Marche , Ancona, Italy .
- 5 Department of Animal Reproduction and Radiology, FMVZ, UNESP , Botucatu, San Paolo, Brazil .
- 6 Centro di Ricerca E. Menni, Fondazione Poliambulanza, Istituto Ospedaliero , Brescia, Italy .
- 6 Centro di Ricerca E. Menni, Fondazione Poliambulanza, Istituto Ospedaliero , Brescia, Italy .
- 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
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