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Frontiers in bioengineering and biotechnology2023; 11; 1204737; doi: 10.3389/fbioe.2023.1204737

Effect of pro-inflammatory cytokine priming and storage temperature of the mesenchymal stromal cell (MSC) secretome on equine articular chondrocytes.

Abstract: Osteoarthritis (OA) is an invalidating articular disease characterized by cartilage degradation and inflammatory events. In horses, OA is associated with up to 60% of lameness and leads to reduced animal welfare along with extensive economic losses; currently, there are no curative therapies to treat OA. The mesenchymal stromal cell (MSC) secretome exhibits anti-inflammatory properties, making it an attractive candidate for improving the management of OA. In this study, we determined the best storage conditions for conditioned media (CMs) and tested whether priming MSCs with cytokines can enhance the properties of the MSC secretome. First, properties of CMs collected from bone-marrow MSC cultures and stored at -80°C, -20°C, 4°C, 20°C or 37°C were assessed on 3D cultures of equine articular chondrocytes (eACs). Second, we primed MSCs with IL-1β, TNF-α or IFN-γ, and evaluated the MSC transcript levels of immunomodulatory effectors and growth factors. The primed CMs were also harvested for subsequent treatment of eACs, either cultured in monolayers or as 3D cell cultures. Finally, we evaluated the effect of CMs on the proliferation and the phenotype of eACs and the quality of the extracellular matrix of the neosynthesized cartilage. CM storage at -80°C, -20°C, and 4°C improved collagen protein accumulation, cell proliferation and the downregulation of inflammation. The three cytokines chosen for the MSC priming influenced MSC immunomodulator gene expression, although each cytokine led to a different pattern of MSC immunomodulation. The cytokine-primed CM had no major effect on eAC proliferation, with IL-1β and TNF-α slightly increasing collagen (types IIB and I) accumulation in eAC 3D cultures (particularly with the CM derived from MSCs primed with IL-1β), and IFN-γ leading to a marked decrease. IL-1β-primed CMs resulted in increased eAC transcript levels of and , whereas IFNγ-primed CMs decreased the levels of and . Although the three cytokines differentially affected the expression of immunomodulatory molecules, primed CMs induced a distinct effect on eACs according to the cytokine used for MSC priming. Different mechanisms seemed to be triggered by each priming cytokine, highlighting the need for further investigation. Nevertheless, this study demonstrates the potential of MSC-CMs for improving equine OA management.
Copyright © 2023 Jammes, Contentin, Audigié, Cassé and Galéra.
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Publication Date: 2023-08-31 PubMed ID: 37720315PubMed Central: PMC10502223DOI: 10.3389/fbioe.2023.1204737Google Scholar: Lookup
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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.

This research focuses on understanding how the secretome from mesenchymal stromal cells (MSCs), when exposed to certain cytokines and stored at optimal conditions, could potentially improve the treatment of osteoarthritis in horses.

Significance of the Study

  • Osteoarthritis is a debilitating joint disease that often leads to cartilage damage and inflammation. In the equine world, it’s responsible for up to 60% of lameness, negatively impacting animal welfare and resulting in financial loss.
  • Currently, there are no curative therapies for osteoarthritis, making this research of significant importance.
  • The prime focus of this study is on the secretome of mesenchymal stromal cells (MSCs), which is known for its anti-inflammatory properties. Therefore, it shows promise in managing osteoarthritis.

Research Methodology

  • The study aimed to identify the best storage conditions for conditioned media (CMs) and to determine if ‘priming’ MSCs with cytokines could enhance the secretome’s properties.
  • To do this, CMs were collected from bone-marrow MSC cultures and stored at various temperatures. Then, these CMs were assessed on 3D cultures of equine articular chondrocytes (eACs).
  • The researchers also primed MSCs with IL-1β, TNF-α or IFN-γ. They then evaluated the MSC transcript levels, harvested the primed CMs, and used them to treat eACs in culture, either monolayered or 3D.
  • Finally, the researchers evaluated the CMs’ effect on eAC proliferation, phenotype, and the quality of the newly synthesized cartilage’s extracellular matrix.

Key Findings

  • The best storage conditions for the CMs were -80°C, -20°C, and 4°C, which improved collagen protein accumulation, cell proliferation and the downregulation of inflammation.
  • The specific cytokines used for MSC priming noticeably influenced MSC immunomodulator gene expression. However, each cytokine induced a different immunomodulation pattern in MSCs.
  • The cytokine-primed CMs did not majorly affect eAC proliferation. IL-1β and TNF-α slightly increased collagen accumulation in eAC 3D cultures, particularly with the CM from MSCs primed with IL-1β. Meanwhile, IFN-γ caused a significant decrease.
  • IL-1β-primed and IFNγ-primed CMs had different effects on eAC transcript levels, demonstrating distinct effects on eACs based on the cytokine used for MSC priming.

Conclusion and Implication

  • Although each priming cytokine triggered different immunomodulatory mechanisms, it’s clear that primed CMs could potentially become an efficient player in managing equine osteoarthritis.
  • The findings underline the importance of further research in this area to clarify the mechanisms triggered by each priming cytokine.

Cite This Article

APA
Jammes M, Contentin R, Audigié F, Cassé F, Galéra P. (2023). Effect of pro-inflammatory cytokine priming and storage temperature of the mesenchymal stromal cell (MSC) secretome on equine articular chondrocytes. Front Bioeng Biotechnol, 11, 1204737. https://doi.org/10.3389/fbioe.2023.1204737

Publication

Frontiers in bioengineering and biotechnology
ISSN: 2296-4185
NlmUniqueID: 101632513
Country: Switzerland
Language: English
Volume: 11
Pages: 1204737
PII: 1204737

Researcher Affiliations

Jammes, Manon
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.
Contentin, Romain
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.
Audigié, Fabrice
  • Unit Under Contract 957 Equine Biomechanics and Locomotor Disorders (USC 957 BPLC), Center of Imaging and Research on Locomotor Affections on Equines (CIRALE), French National Research Institute for Agriculture Food and Environment (INRAE), École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
Cassé, Frédéric
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.
Galéra, Philippe
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 72 references
  1. Abramoff B, Caldera F E. Osteoarthritis: pathology, diagnosis, and treatment options. Med. Clin. North Am. 104 (2), 293–311.
    doi: 10.1016/j.mcna.2019.10.007pubmed: 32035570google scholar: lookup
  2. Barrachina L, Remacha A R, Romero A, Vázquez F J, Albareda J, Prades M. Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties. Vet. Immunol. Immunopathol. 171, 57–65.
    doi: 10.1016/j.vetimm.2016.02.007pubmed: 26964718google scholar: lookup
  3. Barrachina L, Remacha A R, Romero A, Vázquez F J, Albareda J, Prades M. Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments. J. Vet. Sci. 18 (1), 39–49.
    doi: 10.4142/jvs.2017.18.1.39pmc: PMC5366301pubmed: 27297420google scholar: lookup
  4. Barrachina L, Remacha A R, Romero A, Vázquez F J, Albareda J, Prades M. Priming equine bone marrow-derived mesenchymal stem cells with proinflammatory cytokines: implications in immunomodulation-immunogenicity balance, cell viability, and differentiation potential. Stem Cells Dev. 26 (1), 15–24.
    doi: 10.1089/scd.2016.0209pubmed: 27712399google scholar: lookup
  5. Bertoni L, Branly T, Jacquet S, Desancé M, Desquilbet L, Rivory P. Intra-articular injection of 2 different dosages of autologous and allogeneic bone marrow- and umbilical cord-derived mesenchymal stem cells triggers a variable inflammatory response of the fetlock joint on 12 sound experimental horses. Stem Cells Int. 2019, 1–17.
    doi: 10.1155/2019/9431894pmc: PMC6525957pubmed: 31191689google scholar: lookup
  6. Bertoni L, Jacquet-Guibon S, Branly T, Desancé M, Legendre F, Melin M. Evaluation of allogeneic bone-marrow-derived and umbilical cord blood-derived mesenchymal stem cells to prevent the development of osteoarthritis in an equine model. Int. J. Mol. Sci. 22 (5), 2499.
    doi: 10.3390/ijms22052499pmc: PMC7958841pubmed: 33801461google scholar: lookup
  7. Bhat M Y, Solanki H S, Advani J, Khan A A, Keshava Prasad T S, Gowda H. Comprehensive network map of interferon gamma signaling. J. Cell. Commun. Signal 12 (4), 745–751.
    doi: 10.1007/s12079-018-0486-ypmc: PMC6235777pubmed: 30191398google scholar: lookup
  8. Bourdon B, Contentin R, Cassé F, Maspimby C, Oddoux S, Noël A. Marine collagen hydrolysates downregulate the synthesis of pro-catabolic and pro-inflammatory markers of osteoarthritis and favor collagen production and metabolic activity in equine articular chondrocyte organoids. Int. J. Mol. Sci. 22 (2), 580.
    doi: 10.3390/ijms22020580pmc: PMC7826754pubmed: 33430111google scholar: lookup
  9. Branly T, Bertoni L, Contentin R, Rakic R, Gomez-Leduc T, Desancé M. Characterization and use of equine bone marrow mesenchymal stem cells in equine cartilage engineering. Study of their hyaline cartilage forming potential when cultured under hypoxia within a biomaterial in the presence of BMP-2 and TGF-ß1. Stem Cell. Rev. Rep. 13 (5), 611–630.
    doi: 10.1007/s12015-017-9748-ypubmed: 28597211google scholar: lookup
  10. Branly T, Contentin R, Desancé M, Jacquel T, Bertoni L, Jacquet S. Improvement of the chondrocyte-specific phenotype upon equine bone marrow mesenchymal stem cell differentiation: influence of culture time, transforming growth factors and type I collagen siRNAs on the differentiation index. Int. J. Mol. Sci. 19 (2), 435.
    doi: 10.3390/ijms19020435pmc: PMC5855657pubmed: 29389887google scholar: lookup
  11. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N. Engl. J. Med. 331 (14), 889–895.
    doi: 10.1056/NEJM199410063311401pubmed: 8078550google scholar: lookup
  12. Caffi V, Espinosa G, Gajardo G, Morales N, Durán M C, Uberti B. Pre-conditioning of equine bone marrow-derived mesenchymal stromal cells increases their immunomodulatory capacity. Front. Vet. Sci. 7, 318.
    doi: 10.3389/fvets.2020.00318pmc: PMC7325884pubmed: 32656251google scholar: lookup
  13. Cassano J M, Schnabel L V, Goodale M B, Fortier L A. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment. Stem Cell. Res. Ther. 9 (1), 82.
    doi: 10.1186/s13287-018-0840-2pmc: PMC5883371pubmed: 29615127google scholar: lookup
  14. Cequier A, Vázquez F J, Romero A, Vitoria A, Bernad E, García-Martínez M. The immunomodulation–immunogenicity balance of equine Mesenchymal Stem Cells (MSCs) is differentially affected by the immune cell response depending on inflammatory licensing and major histocompatibility complex (MHC) compatibility. Front. Vet. Sci. 9, 957153.
    doi: 10.3389/fvets.2022.957153pmc: PMC9632425pubmed: 36337202google scholar: lookup
  15. Chen S, Sun F, Qian H, Xu W, Jiang J. Preconditioning and engineering strategies for improving the efficacy of mesenchymal stem cell-derived exosomes in cell-free therapy. Stem Cells Int. 2022, 1–18.
    doi: 10.1155/2022/1779346pmc: PMC9124131pubmed: 35607400google scholar: lookup
  16. Cokelaere S, Malda J, van Weeren R. Cartilage defect repair in horses: current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach. Vet. J. 214, 61–71.
    doi: 10.1016/j.tvjl.2016.02.005pubmed: 27387728google scholar: lookup
  17. Colombini A, Perucca Orfei C, Kouroupis D, Ragni E, De Luca P, ViganÒ M. Mesenchymal stem cells in the treatment of articular cartilage degeneration: new biological insights for an old-timer cell. Cytotherapy 21 (12), 1179–1197.
    doi: 10.1016/j.jcyt.2019.10.004pubmed: 31784241google scholar: lookup
  18. Contentin R, Demoor M, Concari M, Desancé M, Audigié F, Branly T. Comparison of the chondrogenic potential of mesenchymal stem cells derived from bone marrow and umbilical cord blood intended for cartilage tissue engineering. Stem Cell. Rev. Rep. 16 (1), 126–143.
    doi: 10.1007/s12015-019-09914-2pubmed: 31745710google scholar: lookup
  19. Contentin R, Jammes M, Bourdon B, Cassé F, Bianchi A, Audigié F. Bone marrow MSC secretome increases equine articular chondrocyte collagen accumulation and their migratory capacities. Int. J. Mol. Sci. 23 (10), 5795.
    doi: 10.3390/ijms23105795pmc: PMC9146805pubmed: 35628604google scholar: lookup
  20. Contino E K. Management and rehabilitation of joint disease in sport horses. Vet. Clin. North Am. Equine Pract. 34 (2), 345–358.
    doi: 10.1016/j.cveq.2018.04.007pubmed: 29793734google scholar: lookup
  21. Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci. Rep. 7 (1), 16214.
    doi: 10.1038/s41598-017-15376-8pmc: PMC5701135pubmed: 29176667google scholar: lookup
  22. Crisostomo P R, Wang Y, Markel T A, Wang M, Lahm T, Meldrum D R. Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. Am. J. Physiol. Cell. Physiol. 294 (3), C675–C682.
    doi: 10.1152/ajpcell.00437.2007pubmed: 18234850google scholar: lookup
  23. Cullier A, Cassé F, Manivong S, Contentin R, Legendre F, Garcia A A. Functionalized nanogels with endothelin-1 and bradykinin receptor antagonist peptides decrease inflammatory and cartilage degradation markers of osteoarthritis in a horse organoid model of cartilage. Int. J. Mol. Sci. 23 (16), 8949.
    doi: 10.3390/ijms23168949pmc: PMC9408731pubmed: 36012214google scholar: lookup
  24. De Luna A, Otahal A, Nehrer S. Mesenchymal stromal cell-derived extracellular vesicles - silver linings for cartilage regeneration?. Front. Cell. Dev. Biol. 8, 593386.
    doi: 10.3389/fcell.2020.593386pmc: PMC7758223pubmed: 33363147google scholar: lookup
  25. Del Amo C, Perez-Valle A, Atilano L, Andia I. Unraveling the signaling secretome of platelet-rich plasma: towards a better understanding of its therapeutic potential in knee osteoarthritis. J. Clin. Med. 11 (3), 473.
    doi: 10.3390/jcm11030473pmc: PMC8836812pubmed: 35159924google scholar: lookup
  26. Demoor M, Ollitrault D, Gomez-Leduc T, Bouyoucef M, Hervieu M, Fabre H. Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction. Biochim. Biophys. Acta 1840 (8), 2414–2440.
    doi: 10.1016/j.bbagen.2014.02.030pubmed: 24608030google scholar: lookup
  27. Even K M, Gaesser A M, Ciamillo S A, Linardi R L, Ortved K F. Comparing the immunomodulatory properties of equine BM-MSCs culture expanded in autologous platelet lysate, pooled platelet lysate, equine serum and fetal bovine serum supplemented culture media. Front. Vet. Sci. 9, 958724.
    doi: 10.3389/fvets.2022.958724pmc: PMC9453159pubmed: 36090170google scholar: lookup
  28. Fernandes T L, Gomoll A H, Lattermann C, Hernandez A J, Bueno D F, Amano M T. Macrophage: A potential target on cartilage regeneration. Front. Immunol. 11, 111.
    doi: 10.3389/fimmu.2020.00111pmc: PMC7026000pubmed: 32117263google scholar: lookup
  29. Gelibter S, Marostica G, Mandelli A, Siciliani S, Podini P, Finardi A. The impact of storage on extracellular vesicles: A systematic study. J. Extracell. Vesicles 11 (2), e12162.
    doi: 10.1002/jev2.12162pmc: PMC8804350pubmed: 35102719google scholar: lookup
  30. Giannasi C, Niada S, Magagnotti C, Ragni E, Andolfo A, Brini A T. Comparison of two ASC-derived therapeutics in an in vitro OA model: secretome versus extracellular vesicles. Stem Cell. Res. Ther. 11 (1), 521.
    doi: 10.1186/s13287-020-02035-5pmc: PMC7711257pubmed: 33272318google scholar: lookup
  31. Goodrich L R, Nixon A J. Medical treatment of osteoarthritis in the horse - a review. Vet. J. 171 (1), 51–69.
    doi: 10.1016/j.tvjl.2004.07.008pubmed: 16427582google scholar: lookup
  32. Hackel A, Aksamit A, Bruderek K, Lang S, Brandau S. TNF-α and IL-1β sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment. Eur. J. Immunol. 51 (2), 319–330.
    doi: 10.1002/eji.201948336pubmed: 32845509google scholar: lookup
  33. Hade M D, Suire C N, Suo Z. Mesenchymal stem cell-derived exosomes: applications in regenerative medicine. Cells 10 (8), 1959.
    doi: 10.3390/cells10081959pmc: PMC8393426pubmed: 34440728google scholar: lookup
  34. Herberts C A, Kwa M S, Hermsen H P. Risk factors in the development of stem cell therapy. J. Transl. Med. 9 (1), 29.
    doi: 10.1186/1479-5876-9-29pmc: PMC3070641pubmed: 21418664google scholar: lookup
  35. Hill J A, Cassano J M, Goodale M B, Fortier L A. Antigenicity of mesenchymal stem cells in an inflamed joint environment. Am. J. Vet. Res. 78 (7), 867–875.
    doi: 10.2460/ajvr.78.7.867pubmed: 28650243google scholar: lookup
  36. Hunter D J, Bierma-Zeinstra S. Osteoarthr. Lancet. 393 (10182), 1745–1759.
    doi: 10.1016/S0140-6736(19)30417-9pubmed: 31034380google scholar: lookup
  37. Jammes M, Contentin R, Cassé F, Galéra P. Equine osteoarthritis: strategies to enhance mesenchymal stromal cell-based acellular therapies. Front. Vet. Sci. 10, 1115774.
    doi: 10.3389/fvets.2023.1115774pmc: PMC9950114pubmed: 36846261google scholar: lookup
  38. Jenei-Lanzl Z, Meurer A, Zaucke F. Interleukin-1β signaling in osteoarthritis - chondrocytes in focus. Cell. Signal 53, 212–223.
    doi: 10.1016/j.cellsig.2018.10.005pubmed: 30312659google scholar: lookup
  39. Jeyaram A, Jay S M. Preservation and storage stability of extracellular vesicles for therapeutic applications. AAPS J. 20 (1), 1.
    doi: 10.1208/s12248-017-0160-ypmc: PMC6582961pubmed: 29181730google scholar: lookup
  40. Joswig A J, Mitchell A, Cummings K J, Levine G J, Gregory C A, Smith R. Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model. Stem Cell. Res. Ther. 8 (1), 42.
    doi: 10.1186/s13287-017-0503-8pmc: PMC5329965pubmed: 28241885google scholar: lookup
  41. Kearney C M, Khatab S, van Buul G M, Plomp S G M, Korthagen N M, Labberté M C. Treatment effects of intra-articular allogenic mesenchymal stem cell secretome in an equine model of joint inflammation. Front. Vet. Sci. 9, 907616.
    doi: 10.3389/fvets.2022.907616pmc: PMC9257274pubmed: 35812845google scholar: lookup
  42. Kim M, Shin D I, Choi B H, Min B H. Exosomes from IL-1β-primed mesenchymal stem cells inhibited IL-1β- and TNF-α-mediated inflammatory responses in osteoarthritic SW982 cells. Tissue Eng. Regen. Med. 18, 525–536.
    doi: 10.1007/s13770-020-00324-xpmc: PMC8325746pubmed: 33495946google scholar: lookup
  43. Kudlik G, Hegyi B, Czibula A, Monostori É, Buday L, Uher F. Mesenchymal stem cells promote macrophage polarization toward M2b-like cells. Exp. Cell. Res. 348 (1), 36–45.
    doi: 10.1016/j.yexcr.2016.08.022pubmed: 27578361google scholar: lookup
  44. Kumar P, Kandoi S, Misra R, Verma R S. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev. 46, 1–9.
    doi: 10.1016/j.cytogfr.2019.04.002pubmed: 30954374google scholar: lookup
  45. Laggner M, Gugerell A, Bachmann C, Hofbauer H, Vorstandlechner V, Seibold M. Reproducibility of GMP-compliant production of therapeutic stressed peripheral blood mononuclear cell-derived secretomes, a novel class of biological medicinal products. Stem Cell. Res. Ther. 11 (1), 9.
    doi: 10.1186/s13287-019-1524-2pmc: PMC6942406pubmed: 31900195google scholar: lookup
  46. Li H, Ghazanfari R, Zacharaki D, Lim H C, Scheding S. Isolation and characterization of primary bone marrow mesenchymal stromal cells. Ann. N. Y. Acad. Sci. 1370 (1), 109–118.
    doi: 10.1111/nyas.13102pubmed: 27270495google scholar: lookup
  47. Lin Z, Fitzgerald J B, Xu J, Willers C, Wood D, Grodzinsky A J. Gene expression profiles of human chondrocytes during passaged monolayer cultivation. J. Orthop. Res. 26 (9), 1230–1237.
    doi: 10.1002/jor.20523pubmed: 18404652google scholar: lookup
  48. Ling Y, Zhang W, Wang P, Xie W, Yang W, Wang D A. Three-dimensional (3D) hydrogel serves as a platform to identify potential markers of chondrocyte dedifferentiation by combining RNA sequencing. Bioact. Mater 6 (9), 2914–2926.
    doi: 10.1016/j.bioactmat.2021.02.018pmc: PMC7917462pubmed: 33718672google scholar: lookup
  49. Liu C, Li Y, Yang Z, Zhou Z, Lou Z, Zhang Q. Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair. Nanomedicine (Lond) 15 (3), 273–288.
    doi: 10.2217/nnm-2019-0208pubmed: 31789105google scholar: lookup
  50. Liu X, Yang Y, Li Y, Niu X, Zhao B, Wang Y. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale 9 (13), 4430–4438.
    doi: 10.1039/c7nr00352hpubmed: 28300264google scholar: lookup
  51. López-García L, Castro-Manrreza M E. TNF-Α and IFN-γ participate in improving the immunoregulatory capacity of mesenchymal stem/stromal cells: importance of cell–cell contact and extracellular vesicles. Int. J. Mol. Sci. 22 (17), 9531.
    doi: 10.3390/ijms22179531pmc: PMC8431422pubmed: 34502453google scholar: lookup
  52. Mardpour S, Hamidieh A A, Taleahmad S, Sharifzad F, Taghikhani A, Baharvand H. Interaction between mesenchymal stromal cell-derived extracellular vesicles and immune cells by distinct protein content. J. Cell. Physiol. 234 (6), 8249–8258.
    doi: 10.1002/jcp.27669pubmed: 30378105google scholar: lookup
  53. Maumus M, Roussignol G, Toupet K, Penarier G, Bentz I, Teixeira S. Utility of a mouse model of osteoarthritis to demonstrate cartilage protection by ifnγ-primed equine mesenchymal stem cells. Front. Immunol. 7, 392.
    doi: 10.3389/fimmu.2016.00392pmc: PMC5037129pubmed: 27729913google scholar: lookup
  54. McIlwraith C W, Frisbie D D, Kawcak C E. The horse as a model of naturally occurring osteoarthritis. Bone Jt. Res. 1 (11), 297–309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  55. Muhammad S A, Nordin N, Mehat M Z, Fakurazi S. Comparative efficacy of stem cells and secretome in articular cartilage regeneration: A systematic review and meta-analysis. Cell. Tissue Res. 375 (2), 329–344.
    doi: 10.1007/s00441-018-2884-0pubmed: 30084022google scholar: lookup
  56. O’Connell B, Wragg N M, Wilson S L. The use of PRP injections in the management of knee osteoarthritis. Cell. Tissue Res. 376 (2), 143–152.
    doi: 10.1007/s00441-019-02996-xpubmed: 30758709google scholar: lookup
  57. Polur I, Lee P L, Servais J M, Xu L, Li Y. Role of HTRA1, a serine protease, in the progression of articular cartilage degeneration. Histol. Histopathol. 25 (5), 599–608.
    doi: 10.14670/HH-25.599pmc: PMC2894561pubmed: 20238298google scholar: lookup
  58. Qin B, Zhang Q, Hu X M, Mi T Y, Yu H Y, Liu S S. How does temperature play a role in the storage of extracellular vesicles?. J. Cell. Physiol. 235 (11), 7663–7680.
    doi: 10.1002/jcp.29700pubmed: 32324279google scholar: lookup
  59. Rakic R, Bourdon B, Hervieu M, Branly T, Legendre F, Saulnier N. RNA interference and BMP-2 stimulation allows equine chondrocytes redifferentiation in 3D-hypoxia cell culture model: application for matrix-induced autologous chondrocyte implantation. Int. J. Mol. Sci. 18 (9), 1842.
    doi: 10.3390/ijms18091842pmc: PMC5618491pubmed: 28837082google scholar: lookup
  60. Rasmusson I. Immune modulation by mesenchymal stem cells. Exp. Cell. Res. 312 (12), 2169–2179.
    doi: 10.1016/j.yexcr.2006.03.019pubmed: 16631737google scholar: lookup
  61. Ren S, Wang C, Guo S. Review of the role of mesenchymal stem cells and exosomes derived from mesenchymal stem cells in the treatment of orthopedic disease. Med. Sci. Monit. 28, 9359377–e936011.
    doi: 10.12659/MSM.935937pmc: PMC9063455pubmed: 35477700google scholar: lookup
  62. Shi Y, Su J, Roberts A I, Shou P, Rabson A B, Ren G. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 33 (3), 136–143.
    doi: 10.1016/j.it.2011.11.004pmc: PMC3412175pubmed: 22227317google scholar: lookup
  63. Szabó E, Fajka-Boja R, Kriston-Pal E, Hornung A, Makra I, Kudlik G. Licensing by inflammatory cytokines abolishes heterogeneity of immunosuppressive function of mesenchymal stem cell population. Stem Cells Dev. 24 (18), 2171–2180.
    doi: 10.1089/scd.2014.0581pubmed: 26153898google scholar: lookup
  64. Tetlow L C, Adlam D J, Woolley D E. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 44 (3), 585–594.
    doi: 10.1002/1529-0131(200103)44:3<585:aid-anr107>3.0.co;2-cpubmed: 11263773google scholar: lookup
  65. Toh W S, Lai R C, Hui J H P, Lim S K. MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. Semin. Cell. Dev. Bio 67, 56–64.
    doi: 10.1016/j.semcdb.2016.11.008pubmed: 27871993google scholar: lookup
  66. Velot É, Madry H, Venkatesan J K, Bianchi A, Cucchiarini M. Is extracellular vesicle-based therapy the next answer for cartilage regeneration?. Front. Bioeng. Biotechnol. 9, 645039.
    doi: 10.3389/fbioe.2021.645039pmc: PMC8102683pubmed: 33968913google scholar: lookup
  67. Voskamp C, Koevoet W J L M, Somoza R A, Caplan A I, Lefebvre V, van Osch G J V M. Enhanced chondrogenic capacity of mesenchymal stem cells after TNFα pre-treatment. Front. Bioeng. Biotechnol. 8, 658.
    doi: 10.3389/fbioe.2020.00658pmc: PMC7344141pubmed: 32714905google scholar: lookup
  68. Wang Y, Yu D, Liu Z, Zhou F, Dai J, Wu B. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell. Res. Ther. 8 (1), 189.
    doi: 10.1186/s13287-017-0632-0pmc: PMC5556343pubmed: 28807034google scholar: lookup
  69. Webster J D, Vucic D. The balance of TNF mediated pathways regulates inflammatory cell death signaling in healthy and diseased tissues. Front. Cell. Dev. Biol. 8, 365.
    doi: 10.3389/fcell.2020.00365pmc: PMC7326080pubmed: 32671059google scholar: lookup
  70. Yuan F, Li Y M, Wang Z. Preserving extracellular vesicles for biomedical applications: consideration of storage stability before and after isolation. Drug Deliv. 28 (1), 1501–1509.
    doi: 10.1080/10717544.2021.1951896pmc: PMC8281093pubmed: 34259095google scholar: lookup
  71. Zhang M, Zhou Q, Liang Q Q, Li C G, Holz J D, Tang D. IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways. Osteoarthr. Cartil. 17 (1), 100–106.
    doi: 10.1016/j.joca.2008.05.007pubmed: 18595745google scholar: lookup
  72. Zhao Y, Li Y, Qu R, Chen X, Wang W, Qiu C. Cortistatin binds to TNF-α receptors and protects against osteoarthritis. EBioMedicine 41, 556–570.
    doi: 10.1016/j.ebiom.2019.02.035pmc: PMC6443028pubmed: 30826358google scholar: lookup

Citations

This article has been cited 1 times.
  1. Jammes M, 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 Sep 16;24(18).
    doi: 10.3390/ijms241814169pubmed: 37762473google scholar: lookup
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