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Home / Equine Research Bank / Front Vet Sci / Characterization and priming of equine muscle-derived mesenc...
Frontiers in veterinary science2026; 12; 1741322; doi: 10.3389/fvets.2025.1741322

Characterization and priming of equine muscle-derived mesenchymal stem cells to enhance their anti-inflammatory and immunomodulatory profiles.

Abstract: A minimally invasive microbiopsy-based method for the isolation of mesenchymal stem cells (MSCs) from equine skeletal muscle (M-MSCs) provides a readily accessible source of MSCs for clinical applications. We examined the expression of genes associated with immunomodulation and anti-inflammatory pathways, in addition to those of growth factors and the major histocompatibility complex (MHC) molecules I and II, at constitutive levels and after priming with inflammatory cytokines, an immunostimulant, and heat-shocking. While there was notable variation between the M-MSCs from each of the horses in their constitutive expression of many of the genes examined, and in their responses to the different priming methods, priming with TNF- and IFN- increased the expression of genes associated with anti-inflammatory pathways, immunomodulation, and tissue repair. M-MSCs from all horses constitutively expressed and lacked expression of ; only heat-shocking induced the expression of . The responses to priming, together with their ease of harvesting, supports further investigation into the use of M-MSCs as a therapy for inflammatory and immune-mediated conditions in the horse. However, due to the variability between M-MSCs from different individuals, characterization of the cells before autologous administration, and the selection of those cells most fit-for-purpose in the case of allogeneic transfer, is recommended.
Copyright © 2026 Shahid, Guitart, Bertin, Simon, Ceusters, Serteyn and Whitworth.
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Publication Date: 2026-01-12 PubMed ID: 41602612PubMed Central: PMC12832516DOI: 10.3389/fvets.2025.1741322Google 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.

Overview

  • This study investigates mesenchymal stem cells (MSCs) derived from horse skeletal muscle using a minimally invasive biopsy method.
  • It evaluates how priming these cells with various stimuli enhances their anti-inflammatory and immunomodulatory functions for potential therapeutic use.

Background and Purpose

  • MSCs are multipotent stem cells capable of modulating immune responses and promoting tissue repair.
  • Equine MSCs can be isolated from skeletal muscle using a microbiopsy method (M-MSCs), which is minimally invasive and clinically practical.
  • The goal is to characterize these M-MSCs in terms of gene expression related to immune modulation, inflammation control, growth factors, and major histocompatibility complex (MHC) molecules.
  • Evaluating the baseline (constitutive) expression of these genes and how this changes after priming with inflammatory cytokines, immunostimulants, or heat shock gives insight into how these cells might be optimized for therapeutic use.

Methods

  • M-MSCs were harvested from multiple individual horses using minimally invasive microbiopsy techniques.
  • Gene expression levels were measured for:
    • Immunomodulatory and anti-inflammatory pathways
    • Growth factors linked to tissue repair
    • MHC class I and II molecules (important for immune recognition)
  • Cells were subjected to different priming techniques:
    • Exposure to inflammatory cytokines TNF-α (tumor necrosis factor-alpha) and IFN-γ (interferon-gamma)
    • Exposure to a general immunostimulant
    • Heat-shock treatment
  • Gene expression was then re-assessed to identify changes induced by priming.

Key Findings

  • There was considerable variability in constitutive gene expression profiles between M-MSCs from different horses.
  • Priming with TNF-α and IFN-γ consistently upregulated genes involved in anti-inflammatory responses, immunomodulation, and tissue repair.
  • All M-MSCs constitutively expressed certain genes (these seem to be immunomodulatory or anti-inflammatory, although specific names are missing from the abstract).
  • MHC class I was expressed consistently, while MHC class II was absent at baseline and only induced by heat-shocking.
  • Heat-shock priming could induce additional gene expressions not seen under other conditions, including MHC class II.

Implications for Therapy

  • The findings suggest that M-MSCs can be effectively primed to enhance their therapeutic potential by boosting their anti-inflammatory and immunomodulatory functions.
  • The variability in gene expression profiles among horses indicates a need for pre-treatment characterization of MSCs when using autologous (self-derived) therapies.
  • For allogeneic (donor-derived) therapies, selecting donor cells with optimal gene expression profiles and priming responsiveness is important to ensure efficacy.
  • Because these M-MSCs can be harvested easily and minimally invasively, they represent a promising cell source for treating inflammatory and immune-mediated conditions in horses.

Conclusions and Recommendations

  • M-MSCs show potential as a practical and effective cell therapy for inflammation-related conditions in equine medicine.
  • Priming with inflammatory cytokines like TNF-α and IFN-γ is a promising strategy to enhance their therapeutic properties.
  • However, individual variability requires a tailored approach, including thorough cell characterization before clinical use.
  • Future work is recommended to further explore the therapeutic applications and optimize protocols for MSC priming and selection.

Cite This Article

APA
Shahid MA, Guitart AS, Bertin FR, Simon O, Ceusters J, Serteyn D, Whitworth DJ. (2026). Characterization and priming of equine muscle-derived mesenchymal stem cells to enhance their anti-inflammatory and immunomodulatory profiles. Front Vet Sci, 12, 1741322. https://doi.org/10.3389/fvets.2025.1741322

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 12
Pages: 1741322
PII: 1741322

Researcher Affiliations

Shahid, Muhammad A
  • The University of Queensland, Brisbane, QLD, Australia.
Guitart, Albert Sole
  • The University of Queensland, Brisbane, QLD, Australia.
Bertin, François-René
  • The University of Queensland, Brisbane, QLD, Australia.
Simon, Olivier
  • The University of Adelaide, Adelaide, SA, Australia.
Ceusters, Justine
  • Universite de Liege, Liège, Belgium.
Serteyn, Didier
  • Universite de Liege, Liège, Belgium.
Whitworth, Deanne J
  • The University of Queensland, Brisbane, QLD, Australia.

Conflict of Interest Statement

The method for the isolation and maintenance of the M-MSCs used in this study is patented: Mammalian muscle-derived stem cells, WO2015091210. JC and DS are co-inventors on this patent. The remaining author(s) declared that this work 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 91 references
  1. Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (msc): a comparison of adult and neonatal tissue-derived msc. Cell Commun Signal (2011) 9:12.
    doi: 10.1186/1478-811X-9-12pmc: PMC3117820pubmed: 21569606google scholar: lookup
  2. Klingemann H, Matzilevich D, Marchand J. Mesenchymal stem cells–sources and clinical applications. Transfus Med Hemother (2008) 35:272–7.
    doi: 10.1159/000142333pmc: PMC3076359pubmed: 21512642google scholar: lookup
  3. Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng (2010) 12:87–117.
    doi: 10.1146/annurev-bioeng-070909-105309pmc: PMC3759519pubmed: 20415588google scholar: lookup
  4. Najar M, Raicevic G, Fayyad-Kazan H, Bron D, Toungouz M, Lagneaux L. Mesenchymal stromal cells and immunomodulation: a gathering of regulatory immune cells. Cytotherapy (2016) 18:160–71.
    doi: 10.1016/j.jcyt.2015.10.011pubmed: 26794710google scholar: lookup
  5. Jun G, Guo-sheng L, Cui-yu B, Zhi-min H, Ming-yan H. Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction. Inflammation (2007) 30:97–104.
    doi: 10.1007/s10753-007-9025-3pubmed: 17497204google scholar: lookup
  6. Gerdoni E, Gallo B, Casazza S, Musio S, Bonanni I, Pedemonte E. Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol (2007) 61:219–27.
    doi: 10.1002/ana.21076pubmed: 17387730google scholar: lookup
  7. Munn DH, Mellor AL. Indoleamine 2, 3 dioxygenase and metabolic control of immune responses. Trends Immunol (2013) 34:137–43.
    doi: 10.1016/j.it.2012.10.001pmc: PMC3594632pubmed: 23103127google scholar: lookup
  8. Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther (2019) 10:1–22.
    doi: 10.1186/s13287-019-1165-5pmc: PMC6390367pubmed: 30808416google scholar: lookup
  9. MacDonald ES, Barrett JG. The potential of mesenchymal stem cells to treat systemic inflammation in horses. Front Vet Sci (2020) 6:507.
    doi: 10.3389/fvets.2019.00507pmc: PMC6985200pubmed: 32039250google scholar: lookup
  10. Shahid MA, Kim WH, Kweon O-K. Cryopreservation of heat-shocked canine adipose-derived mesenchymal stromal cells with 10% dimethyl sulfoxide and 40% serum results in better viability, proliferation, anti-oxidation, and in-vitro differentiation. Cryobiology (2020) 92:92–102.
    doi: 10.1016/j.cryobiol.2019.11.040pubmed: 31785238google scholar: lookup
  11. Nava MM, Raimondi MT, Pietrabissa R. Controlling self-renewal and differentiation of stem cells via mechanical cues. Biomed Res Int (2012) 2012:12.
    doi: 10.1155/2012/797410pmc: PMC3471035pubmed: 23091358google scholar: lookup
  12. Huang C, Dai J, Zhang XA. Environmental physical cues determine the lineage specification of mesenchymal stem cells. Biochim Biophys Acta (2015) 1850:1261–6.
    doi: 10.1016/j.bbagen.2015.02.011pmc: PMC4411082pubmed: 25727396google scholar: lookup
  13. Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med (2018) 22:1428–42.
    doi: 10.1111/jcmm.13492pmc: PMC5824372pubmed: 29392844google scholar: lookup
  14. Baldari S, Di Rocco G, Piccoli M, Pozzobon M, Muraca M, Toietta G. Challenges and strategies for improving the regenerative effects of mesenchymal stromal cell-based therapies. Int J Mol Sci (2017) 18:2087.
    doi: 10.3390/ijms18102087pmc: PMC5666769pubmed: 28974046google scholar: lookup
  15. Petrenko Y, Syková E, Kubinová Š. The therapeutic potential of three-dimensional multipotent mesenchymal stromal cell spheroids. Stem Cell Res Ther (2017) 8:1–9.
    doi: 10.1186/s13287-017-0558-6pmc: PMC5406927pubmed: 28446248google scholar: lookup
  16. Barrachina L, Remacha AR, Romero A, Vázquez FJ, 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 (2016) 26:15–24.
    doi: 10.1089/scd.2016.0209pubmed: 27712399google scholar: lookup
  17. Worster AA, Nixon AJ, Brower-Toland BD, Williams J. Effect of transforming growth factor β1 on chondrogenic differentiation of cultured equine mesenchymal stem cells.. Am J Vet Res (2000) 61:1003–10.
    doi: 10.2460/ajvr.2000.61.1003pubmed: 10976727google scholar: lookup
  18. Pourjafar M, Saidijam M, Mansouri K, Ghasemibasir H, Karimi Dermani F, Najafi R. All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo.. Cell Prolif (2017) 50:e12315.
    doi: 10.1111/cpr.12315pmc: PMC6529123pubmed: 27862498google scholar: lookup
  19. Du W, Zhang K, Zhang S, Wang R, Nie Y, Tao H. Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer.. Biomaterials (2017) 133:70–81.
    doi: 10.1016/j.biomaterials.2017.04.030pubmed: 28433939google scholar: lookup
  20. Ranera B, Remacha AR, Álvarez-Arguedas S, Romero A, Vázquez FJ, Zaragoza P. Effect of hypoxia on equine mesenchymal stem cells derived from bone marrow and adipose tissue.. BMC Vet Res (2012) 8:142.
    doi: 10.1186/1746-6148-8-142pmc: PMC3483288pubmed: 22913590google scholar: lookup
  21. Najar M, Krayem M, Merimi M, Burny A, Meuleman N, Bron D. Insights into inflammatory priming of mesenchymal stromal cells: functional biological impacts.. Inflamm Res (2018) 67:467–77.
    doi: 10.1007/s00011-018-1131-1pubmed: 29362849google scholar: lookup
  22. Shahsavari A, Weeratunga P, Ovchinnikov DA, Whitworth DJ. Pluripotency and immunomodulatory signatures of canine induced pluripotent stem cell-derived mesenchymal stromal cells are similar to harvested mesenchymal stromal cells.. Sci Rep (2021) 11:1–18.
    doi: 10.1038/s41598-021-82856-3pmc: PMC7875972pubmed: 33568729google scholar: lookup
  23. Barrachina L, Remacha A, Romero A, Vázquez F, Albareda J, Prades M. Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties.. Vet Immunol Immunopathol (2016) 171:57–65.
    doi: 10.1016/j.vetimm.2016.02.007pubmed: 26964718google scholar: lookup
  24. Ceusters J, Lejeune J-P, Sandersen C, Niesten A, Lagneaux L, Serteyn D. From skeletal muscle to stem cells: an innovative and minimally-invasive process for multiple species.. Sci Rep (2017) 7:696.
    doi: 10.1038/s41598-017-00803-7pmc: PMC5429713pubmed: 28386120google scholar: lookup
  25. Wang Y, Fang J, Liu B, Shao C, Shi Y. Reciprocal regulation of mesenchymal stem cells and immune responses.. Cell Stem Cell (2022) 29:1515–30.
    doi: 10.1016/j.stem.2022.10.001pubmed: 36332569google scholar: lookup
  26. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation.. Cell Stem Cell (2013) 13:392–402.
    doi: 10.1016/j.stem.2013.09.006pubmed: 24094322google scholar: lookup
  27. Han Y, Yang J, Fang J, Zhou Y, Candi E, Wang J. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases.. Signal Transduct Target Ther (2022) 7:92.
    doi: 10.1038/s41392-022-00932-0pmc: PMC8935608pubmed: 35314676google scholar: lookup
  28. Xia Y, Stadler D, Lucifora J, Reisinger F, Webb D, Hösel M. Interferon-γ and tumor necrosis factor-α produced by t cells reduce the hbv persistence form, cccdna, without cytolysis.. Gastroenterology (2016) 150:194–205.
    doi: 10.1053/j.gastro.2015.09.026pubmed: 26416327google scholar: lookup
  29. Cassano JM, Schnabel LV, Goodale MB, Fortier LA. Inflammatory licensed equine mscs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment.. Stem Cell Res Ther (2018) 9:1–13.
    doi: 10.1186/s13287-018-0840-2pmc: PMC5883371pubmed: 29615127google scholar: lookup
  30. Szabó E, Fajka-Boja R, Kriston-Pál É, Hornung Á, Makra I, Kudlik G. Licensing by inflammatory cytokines abolishes heterogeneity of immunosuppressive function of mesenchymal stem cell population.. Stem Cells Dev (2015) 24:2171–80.
    doi: 10.1089/scd.2014.0581pubmed: 26153898google scholar: lookup
  31. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (msc) paradigm: polarization into a pro-inflammatory msc1 or an immunosuppressive msc2 phenotype. PLoS One. (2010) 5:e10088. doi: 10.1371/journal.pone.0010088,
    doi: 10.1371/journal.pone.0010088pmc: PMC2859930pubmed: 20436665google scholar: lookup
  32. Kim WK, Kim WH, Kweon O-K, Kang B-J. Heat-shock proteins can potentiate the therapeutic ability of cryopreserved mesenchymal stem cells for the treatment of acute spinal cord injury in dogs. Stem Cell Rev Rep. (2022) 18:1461–77. doi: 10.1007/s12015-021-10316-6,
    doi: 10.1007/s12015-021-10316-6pubmed: 35001344google scholar: lookup
  33. Mastri M, Shah Z, McLaughlin T, Greene CJ, Baum L, Suzuki G, et al. Activation of toll-like receptor 3 amplifies mesenchymal stem cell trophic factors and enhances therapeutic potency. Am J Physiol Cell Physiol. (2012) 303:C1021–33. doi: 10.1152/ajpcell.00191.2012,
    doi: 10.1152/ajpcell.00191.2012pmc: PMC3492833pubmed: 22843797google scholar: lookup
  34. Re F, Strominger JL. Il-10 released by concomitant tlr2 stimulation blocks the induction of a subset of th1 cytokines that are specifically induced by tlr4 or tlr3 in human dendritic cells. J Immunol. (2004) 173:7548–55. doi: 10.4049/jimmunol.173.12.7548,
    doi: 10.4049/jimmunol.173.12.7548pubmed: 15585882google scholar: lookup
  35. Salem ML, El-Naggar SA, Mobasher MA, Elgharabawy RM. The toll-like receptor 3 agonist polyriboinosinic polyribocytidylic acid increases the numbers of nk cells with distinct phenotype in the liver of b6 mice. J Immunol Res. (2020) 2020:2489407. doi: 10.1155/2020/2489407
    doi: 10.1155/2020/2489407pmc: PMC7077049pubmed: 32211442google scholar: lookup
  36. Dasari P, Nicholson IC, Hodge G, Dandie GW, Zola H. Expression of toll-like receptors on b lymphocytes. Cell Immunol. (2005) 236:140–5. doi: 10.1016/j.cellimm.2005.08.020
    doi: 10.1016/j.cellimm.2005.08.020pubmed: 16188245google scholar: lookup
  37. Cassano JM, Schnabel LV, Goodale MB, Fortier LA. The immunomodulatory function of equine mscs is enhanced by priming through an inflammatory microenvironment or tlr3 ligand. Vet Immunol Immunopathol. (2018) 195:33–9. doi: 10.1016/j.vetimm.2017.10.003,
    doi: 10.1016/j.vetimm.2017.10.003pubmed: 29249315google scholar: lookup
  38. Zhao X, Liu D, Gong W, Zhao G, Liu L, Yang L, et al. The toll-like receptor 3 ligand, poly(i:C), improves immunosuppressive function and therapeutic effect of mesenchymal stem cells on sepsis via inhibiting mir-143. Stem Cells. (2014) 32:521–33. doi: 10.1002/stem.1543,
    doi: 10.1002/stem.1543pubmed: 24105952google scholar: lookup
  39. Souza-Moreira L, Tan Y, Wang Y, Wang J-P, Salkhordeh M, Virgo J, et al. Poly (I:C) enhances mesenchymal stem cell control of myeloid cells from covid-19 patients. IScience. (2022) 25:4188. doi: 10.1016/j.isci.2022.104188
    doi: 10.1016/j.isci.2022.104188pmc: PMC8975597pubmed: 35402859google scholar: lookup
  40. Hwa Cho H, Bae YC, Jung JS. Role of toll-like receptors on human adipose-derived stromal cells. Stem Cells. (2006) 24:2744–52. doi: 10.1634/stemcells.2006-0189,
    doi: 10.1634/stemcells.2006-0189pubmed: 16902195google scholar: lookup
  41. Qiao PF, Yao L, Zhang XC, Li GD, Wu DQ. Heat shock pretreatment improves stem cell repair following ischemia-reperfusion injury via autophagy. World J Gastroenterol. (2015) 21:12822–34. doi: 10.3748/wjg.v21.i45.12822,
    doi: 10.3748/wjg.v21.i45.12822pmc: PMC4671037pubmed: 26668506google scholar: lookup
  42. Zhou J, Wang LP, Feng X, Fan DD, Zang WJ, Wang B. Synthetic peptides from heat-shock protein 65 inhibit proinflammatory cytokine secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients. Clin Exp Pharmacol Physiol. (2014) 41:67–72. doi: 10.1111/1440-1681.12178,
    doi: 10.1111/1440-1681.12178pubmed: 24111596google scholar: lookup
  43. Celis L, Vandevyver C, Geusens P, Dequeker J, Raus J, Zhang J. Clonal expansion of mycobacterial heat-shock protein–reactive t lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients. Arthritis Rheum. (1997) 40:510–9. doi: 10.1002/art.1780400317,
    doi: 10.1002/art.1780400317pubmed: 9082939google scholar: lookup
  44. Yoo C-G, Lee S, Lee C-T, Kim YW, Han SK, Shim Y-S. Anti-inflammatory effect of heat shock protein induction is related to stabilization of iκbα through preventing iκb kinase activation in respiratory epithelial cells. J Immunol. (2000) 164:5416–23. doi: 10.4049/jimmunol.164.10.5416,
    doi: 10.4049/jimmunol.164.10.5416pubmed: 10799907google scholar: lookup
  45. Villar J, Ribeiro SP, Mullen JBM, Kuliszewski M, Post M, Slutsky AS, et al. Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model. Crit Care Med. (1994) 22:917–21. doi: 10.1097/00003246-199406000-00007,
    doi: 10.1097/00003246-199406000-00007pubmed: 8205824google scholar: lookup
  46. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2− δδct method. Methods. (2001) 25:402–8. doi: 10.1006/meth.2001.1262
    doi: 10.1006/meth.2001.1262pubmed: 11846609google scholar: lookup
  47. Spanholtz TA, Theodorou P, Holzbach T, Wutzler S, Giunta RE, Machens H-G. Vascular endothelial growth factor (vegf165) plus basic fibroblast growth factor (bfgf) producing cells induce a mature and stable vascular network—a future therapy for ischemically challenged tissue. J Surg Res. (2011) 171:329–38. doi: 10.1016/j.jss.2010.03.033,
    doi: 10.1016/j.jss.2010.03.033pubmed: 20605609google scholar: lookup
  48. Li P, Ou Q, Shi S, Shao C. Immunomodulatory properties of mesenchymal stem cells/dental stem cells and their therapeutic applications. Cell Mol Immunol. (2023) 20:558–69. doi: 10.1038/s41423-023-00998-y,
    doi: 10.1038/s41423-023-00998-ypmc: PMC10040934pubmed: 36973490google scholar: lookup
  49. González-González A, García-Sánchez D, Dotta M, Rodríguez-Rey JC, Pérez-Campo FM. Mesenchymal stem cells secretome: the cornerstone of cell-free regenerative medicine. World J Stem Cells. (2020) 12:1529–52. doi: 10.4252/wjsc.v12.i12.1529,
    doi: 10.4252/wjsc.v12.i12.1529pmc: PMC7789121pubmed: 33505599google scholar: lookup
  50. Harman RM, Patel RS, Fan JC, Park JE, Rosenberg BR, Van de Walle GR. Single-cell rna sequencing of equine mesenchymal stromal cells from primary donor-matched tissue sources reveals functional heterogeneity in immune modulation and cell motility. Stem Cell Res Ther. (2020) 11:524. doi: 10.1186/s13287-020-02043-5
    doi: 10.1186/s13287-020-02043-5pmc: PMC7716481pubmed: 33276815google scholar: lookup
  51. Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA. Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in mhc class ii expression and capable of inciting an immune response in vitro. Stem Cell Res Ther. (2014) 5:13. doi: 10.1186/scrt402
    doi: 10.1186/scrt402pmc: PMC4055004pubmed: 24461709google scholar: lookup
  52. Cequier A, Vázquez FJ, Romero A, Vitoria A, Bernad E, García-Martínez M, et al. 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. (2022) 9:957153. doi: 10.3389/fvets.2022.957153,
    doi: 10.3389/fvets.2022.957153pmc: PMC9632425pubmed: 36337202google scholar: lookup
  53. Lange-Consiglio A, Romele P, Magatti M, Silini A, Idda A, Martino NA, et al. Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells. Stem Cell Res Ther. (2020) 11:1–14. doi: 10.1186/s13287-020-01611-z
    doi: 10.1186/s13287-020-01611-zpmc: PMC7055152pubmed: 32131892google scholar: lookup
  54. Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B, et al. Pre-conditioning of equine bone marrow-derived mesenchymal stromal cells increases their immunomodulatory capacity. Front Vet Sci. (2020) 7:318. doi: 10.3389/fvets.2020.00318
    doi: 10.3389/fvets.2020.00318pmc: PMC7325884pubmed: 32656251google scholar: lookup
  55. Bétous R, Renoud M-L, Hoede C, Gonzalez I, Jones N, Longy M, et al. Human adipose-derived stem cells expanded under ambient oxygen concentration accumulate oxidative DNA lesions and experience procarcinogenic DNA replication stress. Stem Cells Transl Med. (2016) 6:68–76. doi: 10.5966/sctm.2015-0401
    doi: 10.5966/sctm.2015-0401pmc: PMC5442744pubmed: 28170194google scholar: lookup
  56. Herger N, Heggli I, Mengis T, Devan J, Arpesella L, Brunner F, et al. Impacts of priming on distinct immunosuppressive mechanisms of mesenchymal stromal cells under translationally relevant conditions. Stem Cell Res Ther. (2024) 15:65. doi: 10.1186/s13287-024-03677-5
    doi: 10.1186/s13287-024-03677-5pmc: PMC10916130pubmed: 38443999google scholar: lookup
  57. Tolstova T, Dotsenko E, Kozhin P, Novikova S, Zgoda V, Rusanov A, et al. The effect of tlr3 priming conditions on msc immunosuppressive properties. Stem Cell Res Ther. (2023) 14:344. doi: 10.1186/s13287-023-03579-y
    doi: 10.1186/s13287-023-03579-ypmc: PMC10687850pubmed: 38031182google scholar: lookup
  58. Lv H, Yuan X, Zhang J, Lu T, Yao J, Zheng J, et al. Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing nlrp3 inflammasome activation in macrophages. Stem Cell Res Ther. (2021) 12:290. doi: 10.1186/s13287-021-02328-3
    doi: 10.1186/s13287-021-02328-3pmc: PMC8127288pubmed: 34001255google scholar: lookup
  59. Shi Y, Hu G, Su J, Li W, Chen Q, Shou P, et al. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res. (2010) 20:510–8. doi: 10.1038/cr.2010.44,
    doi: 10.1038/cr.2010.44pubmed: 20368733google scholar: lookup
  60. Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood. (2007) 110:3691–4. doi: 10.1182/blood-2007-02-075481
    doi: 10.1182/blood-2007-02-075481pubmed: 17684157google scholar: lookup
  61. Soares MP, Marguti I, Cunha A, Larsen R. Immunoregulatory effects of ho-1: how does it work? Curr Opin Pharmacol. (2009) 9:482–9. doi: 10.1016/j.coph.2009.05.008,
    doi: 10.1016/j.coph.2009.05.008pubmed: 19586801google scholar: lookup
  62. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hmscs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein tsg-6. Cell Stem Cell. (2009) 5:54–63. doi: 10.1016/j.stem.2009.05.003
    doi: 10.1016/j.stem.2009.05.003pmc: PMC4154377pubmed: 19570514google scholar: lookup
  63. Dorronsoro A, Lang V, Ferrin I, Fernández-Rueda J, Zabaleta L, Pérez-Ruiz E, et al. Intracellular role of il-6 in mesenchymal stromal cell immunosuppression and proliferation. Sci Rep. (2020) 10:21853. doi: 10.1038/s41598-020-78864-4
    doi: 10.1038/s41598-020-78864-4pmc: PMC7736882pubmed: 33318571google scholar: lookup
  64. Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL. Equine mesenchymal stem cells inhibit t cell proliferation through different mechanisms depending on tissue source. Stem Cells Dev. (2014) 23:1258–65. doi: 10.1089/scd.2013.0537,
    doi: 10.1089/scd.2013.0537pubmed: 24438346google scholar: lookup
  65. Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL. Comparative analysis of the immunomodulatory properties of equine adult-derived mesenchymal stem cells. Cell Med. (2012) 4:1–12. doi: 10.3727/215517912X647217,
    doi: 10.3727/215517912X647217pmc: PMC3495591pubmed: 23152950google scholar: lookup
  66. Cortés-Araya Y, Amilon K, Rink BE, Black G, Lisowski Z, Donadeu FX, et al. Comparison of antibacterial and immunological properties of mesenchymal stem/stromal cells from equine bone marrow, endometrium, and adipose tissue. Stem Cells Dev. (2018) 27:1518–25. doi: 10.1089/scd.2017.0241,
    doi: 10.1089/scd.2017.0241pmc: PMC6209426pubmed: 30044182google scholar: lookup
  67. Pricola KL, Kuhn NZ, Haleem-Smith H, Song Y, Tuan RS. Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an erk1/2-dependent mechanism. J Cell Biochem. (2009) 108:577–88. doi: 10.1002/jcb.22289,
    doi: 10.1002/jcb.22289pmc: PMC2774119pubmed: 19650110google scholar: lookup
  68. Matsumoto K, Ema M. Roles of vegf-a signalling in development, regeneration, and tumours. J Biochem. (2014) 156:1–10. doi: 10.1093/jb/mvu031,
    doi: 10.1093/jb/mvu031pubmed: 24839295google scholar: lookup
  69. Marra KG, DeFail AJ, Clavijo-Alvarez JA, Badylak SF, Taieb A, Schipper B, et al. Fgf-2 enhances vascularization for adipose tissue engineering. Plast Reconstr Surg. (2008) 121:72. doi: 10.1097/01.prs.0000305517.93747.72,
    doi: 10.1097/01.prs.0000305517.93747.72pubmed: 18349632google scholar: lookup
  70. Bikfalvi A, Klein S, Pintucci G, Rifkin DB. Biological roles of fibroblast growth factor-2*. Endocr Rev. (1997) 18:26–45. doi: 10.1210/edrv.18.1.0292,
    doi: 10.1210/edrv.18.1.0292pubmed: 9034785google scholar: lookup
  71. Cano A, Eraso P, Mazón MJ, Portillo F. Loxl2 in cancer: a two-decade perspective. Int J Mol Sci. (2023) 24:14405. doi: 10.3390/ijms241814405,
    doi: 10.3390/ijms241814405pmc: PMC10532419pubmed: 37762708google scholar: lookup
  72. Zhang X, Wang Q, Wu J, Wang J, Shi Y, Liu M. Crystal structure of human lysyl oxidase-like 2 (hloxl2) in a precursor state. Proc Natl Acad Sci USA. (2018) 115:3828–33. doi: 10.1073/pnas.1720859115,
    doi: 10.1073/pnas.1720859115pmc: PMC5899467pubmed: 29581294google scholar: lookup
  73. DelaRosa O, Dalemans W, Lombardo E. Toll-like receptors as modulators of mesenchymal stem cells. Front Immunol. (2012) 3:182. doi: 10.3389/fimmu.2012.00182,
    doi: 10.3389/fimmu.2012.00182pmc: PMC3387651pubmed: 22783256google scholar: lookup
  74. Shirjang S, Mansoori B, Solali S, Hagh MF, Shamsasenjan K. Toll-like receptors as a key regulator of mesenchymal stem cell function: an up-to-date review. Cell Immunol. (2017) 315:1–10. doi: 10.1016/j.cellimm.2016.12.005,
    doi: 10.1016/j.cellimm.2016.12.005pubmed: 28284487google scholar: lookup
  75. Raicevic G, Najar M, Stamatopoulos B, De Bruyn C, Meuleman N, Bron D, et al. The source of human mesenchymal stromal cells influences their tlr profile as well as their functional properties. Cell Immunol. (2011) 270:207–16. doi: 10.1016/j.cellimm.2011.05.010,
    doi: 10.1016/j.cellimm.2011.05.010pubmed: 21700275google scholar: lookup
  76. Pezzanite LM, Chow L, Johnson V, Griffenhagen GM, Goodrich L, Dow S. Toll-like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion. Vet Surg. (2021) 50:858–71. doi: 10.1111/vsu.13628,
    doi: 10.1111/vsu.13628pubmed: 33797775google scholar: lookup
  77. Lei J, Wang Z, Hui D, Yu W, Zhou D, Xia W, et al. Ligation of tlr2 and tlr4 on murine bone marrow-derived mesenchymal stem cells triggers differential effects on their immunosuppressive activity. Cell Immunol. (2011) 271:147–56. doi: 10.1016/j.cellimm.2011.06.014,
    doi: 10.1016/j.cellimm.2011.06.014pubmed: 21757189google scholar: lookup
  78. Sangiorgi B, Panepucci RA. Modulation of immunoregulatory properties of mesenchymal stromal cells by toll-like receptors: potential applications on gvhd. Stem Cells Int. (2016) 2016:9434250. doi: 10.1155/2016/9434250
    doi: 10.1155/2016/9434250pmc: PMC5050362pubmed: 27738438google scholar: lookup
  79. Traggiai E, Volpi S, Schena F, Gattorno M, Ferlito F, Moretta L, et al. Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of b cells isolated from healthy donors and systemic lupus erythematosus patients. Stem Cells. (2007) 26:562–9. doi: 10.1634/stemcells.2007-0528
    doi: 10.1634/stemcells.2007-0528pubmed: 18024418google scholar: lookup
  80. Zhang Y, Ravikumar M, Ling L, Nurcombe V, Cool SM. Age-related changes in the inflammatory status of human mesenchymal stem cells: implications for cell therapy. Stem Cell Rep. (2021) 16:694–707. doi: 10.1016/j.stemcr.2021.01.021,
    doi: 10.1016/j.stemcr.2021.01.021pmc: PMC8072029pubmed: 33636113google scholar: lookup
  81. Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. (2014) 32:252–60. doi: 10.1038/nbt.2816,
    doi: 10.1038/nbt.2816pmc: PMC4320647pubmed: 24561556google scholar: lookup
  82. Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW. Immune response to allogeneic equine mesenchymal stromal cells. Stem Cell Res Ther. (2021) 12:1–19. doi: 10.1186/s13287-021-02624-y
    doi: 10.1186/s13287-021-02624-ypmc: PMC8588742pubmed: 34772445google scholar: lookup
  83. Hagymasi AT, Dempsey JP, Srivastava PK. Heat-shock proteins. Curr Protoc Immunol. (2022) 2:e592. doi: 10.1002/cpz1.592,
    doi: 10.1002/cpz1.592pubmed: 36367390google scholar: lookup
  84. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic t-cell responses by indoleamine 2, 3-dioxygenase–mediated tryptophan degradation. Blood. (2004) 103:4619–21. doi: 10.1182/blood-2003-11-3909
    doi: 10.1182/blood-2003-11-3909pubmed: 15001472google scholar: lookup
  85. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, et al. Nitric oxide plays a critical role in suppression of t-cell proliferation by mesenchymal stem cells. Blood. (2007) 109:228–34. doi: 10.1182/blood-2006-02-002246
    doi: 10.1182/blood-2006-02-002246pubmed: 16985180google scholar: lookup
  86. Mellor A. Indoleamine 2, 3 dioxygenase and regulation of t cell immunity. Biochem Biophys Res Commun. (2005) 338:20–4. doi: 10.1016/j.bbrc.2005.08.232,
    doi: 10.1016/j.bbrc.2005.08.232pubmed: 16157293google scholar: lookup
  87. Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, et al. Inhibition of allogeneic t cell proliferation by indoleamine 2, 3-dioxygenase–expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med. (2002) 196:447–57. doi: 10.1084/jem.20020052,
    doi: 10.1084/jem.20020052pmc: PMC2196057pubmed: 12186837google scholar: lookup
  88. Lu L, Bonham CA, Chambers FG, Watkins SC, Hoffman RA, Simmons RL, et al. Induction of nitric oxide synthase in mouse dendritic cells by ifn-gamma, endotoxin, and interaction with allogeneic t cells: nitric oxide production is associated with dendritic cell apoptosis. J Immunol. (1996) 157:3577–86. doi: 10.4049/jimmunol.157.8.3577
    doi: 10.4049/jimmunol.157.8.3577pubmed: 8871658google scholar: lookup
  89. Wang G, Cao K, Liu K, Xue Y, Roberts AI, Li F, et al. Kynurenic acid, an ido metabolite, controls tsg-6-mediated immunosuppression of human mesenchymal stem cells. Cell Death Differ. (2018) 25:1209–23. doi: 10.1038/s41418-017-0006-2,
    doi: 10.1038/s41418-017-0006-2pmc: PMC6030103pubmed: 29238069google scholar: lookup
  90. Quintana AM, Landolt GA, Annis KM, Hussey GS. Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model. Vet Immunol Immunopathol. (2011) 140:226–36. doi: 10.1016/j.vetimm.2010.12.008,
    doi: 10.1016/j.vetimm.2010.12.008pubmed: 21292331google scholar: lookup
  91. Huang H, Lavoie-Lamoureux A, Moran K, Lavoie J-P. Il-4 stimulates the expression of cxcl-8, e-selectin, vegf, and inducible nitric oxide synthase mrna by equine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol. (2007) 292:L1147–54. doi: 10.1152/ajplung.00294.2006,
    doi: 10.1152/ajplung.00294.2006pubmed: 17494951google scholar: lookup

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