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Stem cell research & therapy2022; 13(1); 23; doi: 10.1186/s13287-022-02704-7

Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma.

Abstract: Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were randomly divided into two groups (n = 10), and treated either with a single intrabronchial application of autologous AD-MSC or oral dexamethasone for three weeks. A targeted clinical examination with determination of clinical score, maximal change in pleural pressure during the breathing cycle, and an endoscopic examination of the airways were performed at baseline and three weeks after treatment. Bronchoalveolar lavage fluid was analyzed cytologically, and IL-1β, IL-4, IL-8, IL-17, TNFα and IFNγ mRNA and protein concentrations were measured at baseline and three weeks. The horses were then monitored over one year for recurrence of SEA. A non-inferiority analysis and a linear mixed-effects model were performed to assess differences between treatments. The non-inferiority of AD-MSC treatment was not established. However, AD-MSC administration significantly ameliorated the clinical score (P = 0.01), decreased the expression of IL-17 mRNA (P = 0.05) and IL-1β (P ≤ 0.001), IL-4 (P ≤ 0.001), TNFα (P = 0.02) protein levels, and had a positive long-term effect on SEA-associated clinical signs (P = 0.02). Intrabronchial administration of AD-MSC had limited short-term anti-inflammatory effects but improved the clinical signs of SEA at one year.
© 2022. The Author(s).
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Publication Date: 2022-01-21 PubMed ID: 35063028PubMed Central: PMC8777441DOI: 10.1186/s13287-022-02704-7Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't

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.

The research investigates the effect of using autologous adipose-derived mesenchymal stem cells (AD-MSC) in treating severe equine asthma (SEA). It shows that while AD-MSC treatment was not overwhelming, the results showed some positive effects in short-term anti-inflammatory function and in improving clinical signs of SEA for up to a year.

Research Overview

This study targeted severe equine asthma (SEA), an ongoing breathing disorder in horses proving to be a prominent health concern. The treatment solutions applied now have their limitations—while they can enhance lung function and clinical symptoms for a brief period, they rarely lead to full recovery in terms of the horse’s athletic abilities.

Methodology

  • The researchers initiated a randomized, controlled trial involving 20 adult horses diagnosed with SEA.
  • The horses were put into two groups and treated either with a single intrabronchial application of autologous AD-MSC (stem cells derived from their own fat tissues) or three weeks of oral dexamethasone (a corticosteroid used traditionally to treat inflammatory conditions).
  • Before and three weeks after treatment, the horses underwent clinical examinations, including clinical scoring, airways endoscopic examination, and determination of maximal change in pleural pressure during the breathing cycle.
  • The researchers also examined bronchoalveolar lavage fluid cytologically and measured several inflammatory markers at the mRNA and protein levels.
  • The horses were monitored over one year to watch for SEA recurrence.

Results

  • The results revealed that, while the AD-MSC treatment did not outperform traditional therapy (demonstrated by non-inferiority analysis), it still had substantial effects.
  • It significantly improved the clinical score (a measure of disease severity), brought down the expression levels of IL-17 and other cytokines (immune system messengers that can trigger inflammation) and had a sustained beneficial effect on SEA-associated clinical signs a year following treatment.
  • Furthermore, the AD-MSC treatment displayed minor short-term anti-inflammatory impacts but showed potential for progressively treating SEA effects over a longer period.

Implications

The research forms an essential groundwork in exploring new therapeutic frontiers for SEA, offering hope for a better and more effective long-term solution. While more research is needed to confirm these results and optimize the treatment process, it shows that stem cell-based therapies may offer a suitable alternative in instances where conventional treatments fall short.

Cite This Article

APA
Adamič N, Prpar Mihevc S, Blagus R, Kramarič P, Krapež U, Majdič G, Viel L, Hoffman AM, Bienzle D, Vengust M. (2022). Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma. Stem Cell Res Ther, 13(1), 23. https://doi.org/10.1186/s13287-022-02704-7

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 13
Issue: 1
Pages: 23
PII: 23

Researcher Affiliations

Adamič, Neža
  • Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia.
Prpar Mihevc, Sonja
  • Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia.
Blagus, Rok
  • Institute for Biostatistics and Medical Informatics, Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia.
Kramarič, Petra
  • Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia.
Krapež, Uroš
  • Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia.
Majdič, Gregor
  • Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia.
Viel, Laurent
  • Clinical Studies, University of Guelph, Guelph, ON, Canada.
Hoffman, Andrew M
  • School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bienzle, Dorothee
  • Department of Pathobiology, University of Guelph, Guelph, ON, Canada.
Vengust, Modest
  • Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia. modest.vengust@vf.uni-lj.si.

MeSH Terms

  • Animals
  • Asthma / therapy
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid
  • Horse Diseases / therapy
  • Horses
  • Mesenchymal Stem Cells
  • Transplantation, Autologous

Conflict of Interest Statement

GM is partial owner of Animacel ltd. Other authors have no conflict of interest.

References

This article includes 107 references
  1. Robinson NE. International Workshop on Equine Chronic Airway Disease. Michigan State University 16-18 June 2000.. Equine Vet J 2001 Jan;33(1):5-19.
    pubmed: 11191611doi: 10.2746/042516401776767412google scholar: lookup
  2. Lavoie JP. Recurrent airway obstruction (heaves) and summer-pasture-associated obstructive pulmonary disease. In: McGorum BC, Dixon PM, Robinson NE, Schumacher J, editors: Equine Respiratory Medicine and Surgery. Saunders Elsevier; Amsterdam 2007. p. 565–589.
  3. Aviza G, Ainsworth D, Eicker S, Santiago M, Divers T, Perkins G. Outcome of horses diagnosed with and treated for heaves (recurrent airway obstruction). Equine Vet Educ 2001;13:243–246.
  4. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
    pubmed: 21824219doi: 10.1111/j.1440-1843.2011.02033.xgoogle scholar: lookup
  5. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions.. Front Vet Sci 2020;7:450.
    pmc: PMC7438831pubmed: 32903600doi: 10.3389/fvets.2020.00450google scholar: lookup
  6. Custovic A, Johnston SL, Pavord I, Gaga M, Fabbri L, Bel EH, Le Souëf P, Lötvall J, Demoly P, Akdis CA, Ryan D, Mäkelä MJ, Martinez F, Holloway JW, Saglani S, O'Byrne P, Papi A, Sergejeva S, Magnan A, Del Giacco S, Kalayci O, Hamelmann E, Papadopoulos NG. EAACI position statement on asthma exacerbations and severe asthma.. Allergy 2013 Dec;68(12):1520-31.
    pmc: PMC7159478pubmed: 24410781doi: 10.1111/all.12275google scholar: lookup
  7. Corcoran BM, Foster DJ, Fuentes VL. Feline asthma syndrome: a retrospective study of the clinical presentation in 29 cats.. J Small Anim Pract 1995 Nov;36(11):481-8.
    pubmed: 8587322doi: 10.1111/j.1748-5827.1995.tb02787.xgoogle scholar: lookup
  8. Trzil JE. Feline Asthma: Diagnostic and Treatment Update.. Vet Clin North Am Small Anim Pract 2020 Mar;50(2):375-391.
    pubmed: 31812220doi: 10.1016/j.cvsm.2019.10.002google scholar: lookup
  9. Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
    pmc: PMC4913592pubmed: 26806374doi: 10.1111/jvim.13824google scholar: lookup
  10. Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model.. Am J Respir Cell Mol Biol 2012 Nov;47(5):589-96.
    pubmed: 22721832doi: 10.1165/rcmb.2011-0363ocgoogle scholar: lookup
  11. Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.. Sci Rep 2017 Aug 18;7(1):8843.
    pmc: PMC5562887pubmed: 28821845doi: 10.1038/s41598-017-09414-8google scholar: lookup
  12. Cuming RS, Groover ES, Wooldridge AA, Caldwell FJ. Review of glucocorticoid therapy in horses. Part 1: pharmacology. Equine Vet Educ 2018;30(3):141–50.
  13. Eyre P, Elmes PJ, Strickland S. Corticosteroid-potentiated vascular responses of the equine digit: a possible pharmacologic basis for laminitis.. Am J Vet Res 1979 Jan;40(1):135-8.
    pubmed: 453675
  14. Cohen ND, Carter GK. Steroid hepatopathy in a horse with glucocorticoid-induced hyperadrenocorticism.. J Am Vet Med Assoc 1992 Jun 1;200(11):1682-4.
    pubmed: 1624345
  15. Mair TS. Bacterial pneumonia associated with corticosteroid therapy in three horses.. Vet Rec 1996 Mar 2;138(9):205-7.
    pubmed: 8686153doi: 10.1136/vr.138.9.205google scholar: lookup
  16. Pereira MM, Groover E, Wooldridge A, Caldwell F. Review of glucocorticoid therapy in horses. Part 2: clinical use of systemic glucocorticoids in horses. Equine Vet Educ 2018;30(4):213–24.
  17. Satija NK, Singh VK, Verma YK, Gupta P, Sharma S, Afrin F, Sharma M, Sharma P, Tripathi RP, Gurudutta GU. Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine.. J Cell Mol Med 2009 Nov-Dec;13(11-12):4385-402.
    pmc: PMC4515054pubmed: 19602034doi: 10.1111/j.1582-4934.2009.00857.xgoogle scholar: lookup
  18. Voga M, Adamic N, Vengust M, Majdic G. Stem Cells in Veterinary Medicine-Current State and Treatment Options.. Front Vet Sci 2020;7:278.
    pmc: PMC7326035pubmed: 32656249doi: 10.3389/fvets.2020.00278google scholar: lookup
  19. Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL. Identification of a lineage of multipotent hematopoietic progenitors.. Development 1997 May;124(10):1929-39.
    pubmed: 9169840doi: 10.1242/dev.124.10.1929google scholar: lookup
  20. Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal Stem Cell Migration and Tissue Repair.. Cells 2019 Jul 28;8(8).
    pmc: PMC6721499pubmed: 31357692doi: 10.3390/cells8080784google scholar: lookup
  21. Fujita Y, Kadota T, Araya J, Ochiya T, Kuwano K. Clinical Application of Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapeutics for Inflammatory Lung Diseases.. J Clin Med 2018 Oct 14;7(10).
    pmc: PMC6210470pubmed: 30322213doi: 10.3390/jcm7100355google scholar: lookup
  22. Harrell CR, Sadikot R, Pascual J, Fellabaum C, Jankovic MG, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Mesenchymal Stem Cell-Based Therapy of Inflammatory Lung Diseases: Current Understanding and Future Perspectives.. Stem Cells Int 2019;2019:4236973.
    pmc: PMC6525794pubmed: 31191672doi: 10.1155/2019/4236973google scholar: lookup
  23. Zhang LB, He M. Effect of mesenchymal stromal (stem) cell (MSC) transplantation in asthmatic animal models: A systematic review and meta-analysis.. Pulm Pharmacol Ther 2019 Feb;54:39-52.
    pubmed: 30496803doi: 10.1016/j.pupt.2018.11.007google scholar: lookup
  24. Yen BL, Yen ML, Wang LT, Liu KJ, Sytwu HK. Current status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: Gleaning insights for possible use in COVID-19.. Stem Cells Transl Med 2020 Oct;9(10):1163-1173.
    pmc: PMC7300965pubmed: 32526079doi: 10.1002/sctm.20-0186google scholar: lookup
  25. Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.. Am J Physiol Lung Cell Mol Physiol 2010 Dec;299(6):L760-70.
    pmc: PMC4116401pubmed: 20817776doi: 10.1152/ajplung.00182.2009google scholar: lookup
  26. Lee SH, Jang AS, Kwon JH, Park SK, Won JH, Park CS. Mesenchymal stem cell transfer suppresses airway remodeling in a toluene diisocyanate-induced murine asthma model.. Allergy Asthma Immunol Res 2011 Jul;3(3):205-11.
    pmc: PMC3121063pubmed: 21738887doi: 10.4168/aair.2011.3.3.205google scholar: lookup
  27. Cho KS, Park MK, Kang SA, Park HY, Hong SL, Park HK, Yu HS, Roh HJ. Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma.. Mediators Inflamm 2014;2014:436476.
    pmc: PMC4160627pubmed: 25246732doi: 10.1155/2014/436476google scholar: lookup
  28. Mariñas-Pardo L, Mirones I, Amor-Carro O, Fraga-Iriso R, Lema-Costa B, Cubillo I, Rodríguez Milla MÁ, García-Castro J, Ramos-Barbón D. Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma.. Allergy 2014 Jun;69(6):730-40.
    pmc: PMC4114550pubmed: 24750069doi: 10.1111/all.12392google scholar: lookup
  29. Abreu SC, Antunes MA, Xisto DG, Cruz FF, Branco VC, Bandeira E, Zola Kitoko J, de Araújo AF, Dellatorre-Texeira L, Olsen PC, Weiss DJ, Diaz BL, Morales MM, Rocco PRM. Bone Marrow, Adipose, and Lung Tissue-Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma.. Stem Cells Transl Med 2017 Jun;6(6):1557-1567.
    pmc: PMC5689762pubmed: 28425576doi: 10.1002/sctm.16-0398google scholar: lookup
  30. Hao Y, Ran Y, Lu B, Li J, Zhang J, Feng C, Fang J, Ma R, Qiao Z, Dai X, Xiong W, Liu J, Zhou Q, Hao J, Li R, Dai J. Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells on Canine Radiation-Induced Lung Injury.. Int J Radiat Oncol Biol Phys 2018 Oct 1;102(2):407-416.
    pubmed: 30191872doi: 10.1016/j.ijrobp.2018.05.068google scholar: lookup
  31. Trzil JE, Masseau I, Webb TL, Chang CH, Dodam JR, Liu H, Quimby JM, Dow SW, Reinero CR. Intravenous adipose-derived mesenchymal stem cell therapy for the treatment of feline asthma: a pilot study.. J Feline Med Surg 2016 Dec;18(12):981-990.
    pubmed: 26384398doi: 10.1177/1098612x15604351google scholar: lookup
  32. Ihara K, Fukuda S, Enkhtaivan B, Trujillo R, Perez-Bello D, Nelson C, Randolph A, Alharbi S, Hanif H, Herndon D, Prough D, Enkhbaatar P. Adipose-derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation.. PLoS One 2017;12(10):e0185937.
    pmc: PMC5628899pubmed: 28982177doi: 10.1371/journal.pone.0185937google scholar: lookup
  33. Cardenes N, Aranda-Valderrama P, Carney JP, Sellares Torres J, Alvarez D, Kocyildirim E, Wolfram Smith JA, Ting AE, Lagazzi L, Yu Z, Mason S, Santos E, Lopresti BJ, Rojas M. Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model.. BMJ Open Respir Res 2019;6(1):e000308.
    pmc: PMC6339992pubmed: 30713713doi: 10.1136/bmjresp-2018-000308google scholar: lookup
  34. Barussi FC, Bastos FZ, Leite LM, Fragoso FY, Senegaglia AC, Brofman PR, Nishiyama A, Pimpão CT, Michelotto PV Jr. Intratracheal therapy with autologous bone marrow-derived mononuclear cells reduces airway inflammation in horses with recurrent airway obstruction.. Respir Physiol Neurobiol 2016 Oct;232:35-42.
    pubmed: 27396936doi: 10.1016/j.resp.2016.07.002google scholar: lookup
  35. Murcia RY, Vargas A, Lavoie JP. The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids.. PLoS One 2016;11(5):e0154755.
    pmc: PMC4854453pubmed: 27138006doi: 10.1371/journal.pone.0154755google scholar: lookup
  36. Cornelisse CJ, Robinson NE, Berney CE, Kobe CA, Boruta DT, Derksen FJ. Efficacy of oral and intravenous dexamethasone in horses with recurrent airway obstruction.. Equine Vet J 2004 Jul;36(5):426-30.
    pubmed: 15253084doi: 10.2746/0425164044868413google scholar: lookup
  37. DeLuca L, Erb HN, Young JC, Perkins GA, Ainsworth DM. The effect of adding oral dexamethasone to feed alterations on the airway cell inflammatory gene expression in stabled horses affected with recurrent airway obstruction.. J Vet Intern Med 2008 Mar-Apr;22(2):427-35.
    pubmed: 18346142doi: 10.1111/j.1939-1676.2008.0055.xgoogle scholar: lookup
  38. Ainsworth DM, Cheetham J. Disorders of the respiratory system. In: Reed S, Bayly W, Sellon D, editors. Equine internal medicine. 3. New York: Elsevier Saunders; 2010. pp. 290–371.
  39. Beeler-Marfisi J, Clark ME, Wen X, Sears W, Huber L, Ackerley C, Viel L, Bienzle D. Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses.. Am J Vet Res 2010 Jun;71(6):682-9.
    pubmed: 20513185doi: 10.2460/ajvr.71.6.682google scholar: lookup
  40. Willoughby RA, McDonell WN. Pulmonary function testing in horses.. Vet Clin North Am Large Anim Pract 1979 May;1(1):171-96.
    pubmed: 388831doi: 10.1016/s0196-9846(17)30204-5google scholar: lookup
  41. Klein HJ, Deegen E. The measurement of interpleural pressure - a method to assess lung mechanics in the horse. 1987;4(3):141–7.
  42. Hoffman AM. Clinical application of pulmonary function testing in horses. In: Lekeux P, editor. Equine respiratory diseases. 2002. https://www.ivis.org/library/equine-respiratory-diseases/clinical-application-of-pulmonary-function-testing-horses. Accessed 14 Feb 2021.
  43. Couetil L, Hammer J, Miskovic Feutz M, Nogradi N, Perez-Moreno C, Ivester K. Effects of N-butylscopolammonium bromide on lung function in horses with recurrent airway obstruction.. J Vet Intern Med 2012 Nov-Dec;26(6):1433-8.
    pubmed: 22925156doi: 10.1111/j.1939-1676.2012.00992.xgoogle scholar: lookup
  44. Hoffman AM. Bronchoalveolar lavage: sampling technique and guidelines for cytologic preparation and interpretation.. Vet Clin North Am Equine Pract 2008 Aug;24(2):423-35, vii-viii.
    pubmed: 18652963doi: 10.1016/j.cveq.2008.04.003google scholar: lookup
  45. Beekman L, Tohver T, Dardari R, Léguillette R. Evaluation of suitable reference genes for gene expression studies in bronchoalveolar lavage cells from horses with inflammatory airway disease.. BMC Mol Biol 2011 Jan 28;12:5.
    pmc: PMC3039571pubmed: 21272375doi: 10.1186/1471-2199-12-5google scholar: lookup
  46. Giguère S, Prescott JF. Quantitation of equine cytokine mRNA expression by reverse transcription-competitive polymerase chain reaction.. Vet Immunol Immunopathol 1999 Jan 4;67(1):1-15.
    pubmed: 9950350doi: 10.1016/s0165-2427(98)00212-8google scholar: lookup
  47. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR.. Nucleic Acids Res 2001 May 1;29(9):e45.
    pmc: PMC55695pubmed: 11328886doi: 10.1093/nar/29.9.e45google scholar: lookup
  48. Forlenza M, Kaiser T, Savelkoul HF, Wiegertjes GF. The use of real-time quantitative PCR for the analysis of cytokine mRNA levels.. Methods Mol Biol 2012;820:7-23.
    pubmed: 22131023doi: 10.1007/978-1-61779-439-1_2google scholar: lookup
  49. Picandet V, Léguillette R, Lavoie JP. Comparison of efficacy and tolerability of isoflupredone and dexamethasone in the treatment of horses affected with recurrent airway obstruction ('heaves').. Equine Vet J 2003 Jun;35(4):419-24.
    pubmed: 12880012doi: 10.2746/042516403776014208google scholar: lookup
  50. Pinheiro J, Bates D, DebRoy S, Sarkar D, R Core Team. nlme: Linear and Nonlinear Mixed Effects Models. R package version 3.1–144. 2020. Available from: https://CRAN.R-project.org/package=nlme. Accessed 5 Nov 2020.
  51. Henningsen A. censReg: Censored Regression (Tobit) Models. R package version 0.5–32. 2020. Available from: https://cran.r-project.org/web/packages/censReg/censReg.pdf. Accessed 5 Nov 2020.
  52. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol 1995;57(1):289–300.
  53. R Core Team. R: a language and environment for statistical computing. R version 3.6.3. R Foundation for Statistical Computing, Vienna, Austria. 2020. Available from: https://www.eea.europa.eu/data-and-maps/indicators/oxygen-consuming-substances-in-rivers/r-development-core-team-2006. Accessed 5 Nov 2020.
  54. Therneau T. A package for survival analysis in S. version 2.38. 2015. Available from: https://mran.microsoft.com/snapshot/2017-02-04/web/packages/survival/citation.html. Accessed 5 Nov 2020.
  55. Russell KA, Chow NH, Dukoff D, Gibson TW, LaMarre J, Betts DH, Koch TG. Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.. PLoS One 2016;11(12):e0167442.
    pmc: PMC5131977pubmed: 27907211doi: 10.1371/journal.pone.0167442google scholar: lookup
  56. Bearden RN, Huggins SS, Cummings KJ, Smith R, Gregory CA, Saunders WB. In-vitro characterization of canine multipotent stromal cells isolated from synovium, bone marrow, and adipose tissue: a donor-matched comparative study.. Stem Cell Res Ther 2017 Oct 3;8(1):218.
    pmc: PMC5627404pubmed: 28974260doi: 10.1186/s13287-017-0639-6google scholar: lookup
  57. Sasaki A, Mizuno M, Ozeki N, Katano H, Otabe K, Tsuji K, Koga H, Mochizuki M, Sekiya I. Canine mesenchymal stem cells from synovium have a higher chondrogenic potential than those from infrapatellar fat pad, adipose tissue, and bone marrow.. PLoS One 2018;13(8):e0202922.
    pmc: PMC6107231pubmed: 30138399doi: 10.1371/journal.pone.0202922google scholar: lookup
  58. Tang GN, Li CL, Yao Y, Xu ZB, Deng MX, Wang SY, Sun YQ, Shi JB, Fu QL. MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.. Stem Cells Dev 2016 Jun 15;25(12):883-96.
    pmc: PMC4928133pubmed: 27106170doi: 10.1089/scd.2015.0339google scholar: lookup
  59. Du YM, Zhuansun YX, Chen R, Lin L, Lin Y, Li JG. Mesenchymal stem cell exosomes promote immunosuppression of regulatory T cells in asthma.. Exp Cell Res 2018 Feb 1;363(1):114-120.
    pubmed: 29277503doi: 10.1016/j.yexcr.2017.12.021google scholar: lookup
  60. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.. Cytotherapy 2006;8(4):315-7.
    pubmed: 16923606doi: 10.1080/14653240600855905google scholar: lookup
  61. Holcombe SJ, Jackson C, Gerber V, Jefcoat A, Berney C, Eberhardt S, Robinson NE. Stabling is associated with airway inflammation in young Arabian horses.. Equine Vet J 2001 May;33(3):244-9.
    pubmed: 11352345doi: 10.2746/042516401776249606google scholar: lookup
  62. Robinson NE. Recurrent airway obstruction (Heaves). In: Lekeux P, editor: Equine Respiratory Diseases; IVIS; 2001. Available from: http://www.ivis.org/special_books/Lekeux/robinson/reference.asp. Accessed 17 Mar 2000.
  63. Giguère S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.. Vet Immunol Immunopathol 2002 Mar;85(3-4):147-58.
    pubmed: 11943316doi: 10.1016/s0165-2427(01)00420-2google scholar: lookup
  64. Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B, Erb HN, Antczak DF. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2003 Nov 15;96(1-2):83-91.
    pubmed: 14522137doi: 10.1016/s0165-2427(03)00142-9google scholar: lookup
  65. Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP. Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2005 May 1;105(1-2):25-31.
    pubmed: 15797472doi: 10.1016/j.vetimm.2004.12.013google scholar: lookup
  66. Padoan E, Ferraresso S, Pegolo S, Castagnaro M, Barnini C, Bargelloni L. Real time RT-PCR analysis of inflammatory mediator expression in recurrent airway obstruction-affected horses.. Vet Immunol Immunopathol 2013 Dec 15;156(3-4):190-9.
    pubmed: 24176614doi: 10.1016/j.vetimm.2013.09.020google scholar: lookup
  67. Bullone M, Murcia RY, Lavoie JP. Environmental heat and airborne pollen concentration are associated with increased asthma severity in horses.. Equine Vet J 2016 Jul;48(4):479-84.
    pubmed: 26708931doi: 10.1111/evj.12559google scholar: lookup
  68. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis.. Science 1995 Oct 13;270(5234):286-90.
    pubmed: 7569976doi: 10.1126/science.270.5234.286google scholar: lookup
  69. Barnes PJ. Nuclear factor-kappa B.. Int J Biochem Cell Biol 1997 Jun;29(6):867-70.
    pubmed: 9304801doi: 10.1016/s1357-2725(96)00159-8google scholar: lookup
  70. van der Velden VH. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.. Mediators Inflamm 1998;7(4):229-37.
    pmc: PMC1781857pubmed: 9792333doi: 10.1080/09629359890910google scholar: lookup
  71. Zamorano J, Rivas MD, Pérez-G M. Interleukin-4: a multifunctional cytokine. Inmunologia 2003;22(2):215–224.
  72. Eggenhofer E, Benseler V, Kroemer A, Popp FC, Geissler EK, Schlitt HJ, Baan CC, Dahlke MH, Hoogduijn MJ. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion.. Front Immunol 2012;3:297.
    pmc: PMC3458305pubmed: 23056000doi: 10.3389/fimmu.2012.00297google scholar: lookup
  73. de Witte SFH, Luk F, Sierra Parraga JM, Gargesha M, Merino A, Korevaar SS, Shankar AS, O'Flynn L, Elliman SJ, Roy D, Betjes MGH, Newsome PN, Baan CC, Hoogduijn MJ. Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered Through Phagocytosis of MSC By Monocytic Cells.. Stem Cells 2018 Apr;36(4):602-615.
    pubmed: 29341339doi: 10.1002/stem.2779google scholar: lookup
  74. Horohov DW, Beadle RE, Mouch S, Pourciau SS. Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2005 Oct 18;108(1-2):237-45.
    pubmed: 16098607doi: 10.1016/j.vetimm.2005.07.013google scholar: lookup
  75. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease.. Immunol Rev 2008 Jun;223:87-113.
    pmc: PMC3299089pubmed: 18613831doi: 10.1111/j.1600-065x.2008.00628.xgoogle scholar: lookup
  76. Bond SL, Hundt J, Léguillette R. Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma.. BMC Vet Res 2019 Nov 6;15(1):397.
    pmc: PMC6833259pubmed: 31694631doi: 10.1186/s12917-019-2144-xgoogle scholar: lookup
  77. Beringer A, Noack M, Miossec P. IL-17 in Chronic Inflammation: From Discovery to Targeting.. Trends Mol Med 2016 Mar;22(3):230-241.
    pubmed: 26837266doi: 10.1016/j.molmed.2016.01.001google scholar: lookup
  78. Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease.. Immunology 2010 Mar;129(3):311-21.
    pmc: PMC2826676pubmed: 20409152doi: 10.1111/j.1365-2567.2009.03240.xgoogle scholar: lookup
  79. Khan D, Ansar Ahmed S. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs.. Front Genet 2015;6:236.
    pmc: PMC4500956pubmed: 26236331doi: 10.3389/fgene.2015.00236google scholar: lookup
  80. Park J, Jeong S, Park K, Yang K, Shin S. Expression profile of microRNAs following bone marrow-derived mesenchymal stem cell treatment in lipopolysaccharide-induced acute lung injury.. Exp Ther Med 2018 Jun;15(6):5495-5502.
    pmc: PMC5996665pubmed: 29904430doi: 10.3892/etm.2018.6118google scholar: lookup
  81. Zenobia C, Hajishengallis G. Basic biology and role of interleukin-17 in immunity and inflammation.. Periodontol 2000 2015 Oct;69(1):142-59.
    pmc: PMC4530463pubmed: 26252407doi: 10.1111/prd.12083google scholar: lookup
  82. Alangari AA. Genomic and non-genomic actions of glucocorticoids in asthma.. Ann Thorac Med 2010 Jul;5(3):133-9.
    pmc: PMC2930650pubmed: 20835306doi: 10.4103/1817-1737.65040google scholar: lookup
  83. Knudsen PJ, Dinarello CA, Strom TB. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate.. J Immunol 1986 Nov 15;137(10):3189-94.
    pubmed: 3021848
  84. Schindler R, Clark BD, Dinarello CA. Dissociation between interleukin-1 beta mRNA and protein synthesis in human peripheral blood mononuclear cells.. J Biol Chem 1990 Jun 25;265(18):10232-7.
    pubmed: 2354999
  85. Dokter WH, Esselink MT, Sierdsema SJ, Halie MR, Vellenga E. Transcriptional and posttranscriptional regulation of the interleukin-4 and interleukin-3 genes in human T cells.. Blood 1993 Jan 1;81(1):35-40.
    pubmed: 8417800
  86. Wong CK, Ho CY, Ko FW, Chan CH, Ho AS, Hui DS, Lam CW. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma.. Clin Exp Immunol 2001 Aug;125(2):177-83.
    pmc: PMC1906135pubmed: 11529906doi: 10.1046/j.1365-2249.2001.01602.xgoogle scholar: lookup
  87. Fallon PG, Jolin HE, Smith P, Emson CL, Townsend MJ, Fallon R, Smith P, McKenzie AN. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13.. Immunity 2002 Jul;17(1):7-17.
    pubmed: 12150887doi: 10.1016/s1074-7613(02)00332-1google scholar: lookup
  88. Umland SP, Razac S, Shah H, Nahrebne DK, Egan RW, Billah MM. Interleukin-5 mRNA stability in human T cells is regulated differently than interleukin-2, interleukin-3, interleukin-4, granulocyte/macrophage colony-stimulating factor, and interferon-gamma.. Am J Respir Cell Mol Biol 1998 May;18(5):631-42.
    pubmed: 9569233doi: 10.1165/ajrcmb.18.5.3046google scholar: lookup
  89. Yarovinsky TO, Butler NS, Monick MM, Hunninghake GW. Early exposure to IL-4 stabilizes IL-4 mRNA in CD4+ T cells via RNA-binding protein HuR.. J Immunol 2006 Oct 1;177(7):4426-35.
    pubmed: 16982877doi: 10.4049/jimmunol.177.7.4426google scholar: lookup
  90. Popescu FD, Popescu F. A review of antisense therapeutic interventions for molecular biological targets in asthma.. Biologics 2007 Sep;1(3):271-83.
    pmc: PMC2721314pubmed: 19707336
  91. Ferraiolo BL, Moore JA, Crase D, Gribling P, Wilking H, Baughman RA. Pharmacokinetics and tissue distribution of recombinant human tumor necrosis factor-alpha in mice.. Drug Metab Dispos 1988 Mar-Apr;16(2):270-5.
    pubmed: 2898346
  92. Simó R, Barbosa-Desongles A, Lecube A, Hernandez C, Selva DM. Potential role of tumor necrosis factor-α in downregulating sex hormone-binding globulin.. Diabetes 2012 Feb;61(2):372-82.
    pmc: PMC3266423pubmed: 22210320doi: 10.2337/db11-0727google scholar: lookup
  93. Mahmoud L, Al-Enezi F, Al-Saif M, Warsy A, Khabar KS, Hitti EG. Sustained stabilization of Interleukin-8 mRNA in human macrophages.. RNA Biol 2014;11(2):124-33.
    pmc: PMC3973731pubmed: 24525793doi: 10.4161/rna.27863google scholar: lookup
  94. Montgomery JB, Husulak ML, Kosolofski H, Dos Santos S, Burgess H, Meachem MD. Tumor necrosis factor-alpha protein concentrations in bronchoalveolar lavage fluid from healthy horses and horses with severe equine asthma.. Vet Immunol Immunopathol 2018 Aug;202:70-73.
    pubmed: 30078601doi: 10.1016/j.vetimm.2018.06.014google scholar: lookup
  95. Clark A. Post-transcriptional regulation of pro-inflammatory gene expression.. Arthritis Res 2000;2(3):172-4.
    pmc: PMC129998pubmed: 11094425doi: 10.1186/ar83google scholar: lookup
  96. Mijatovic T, Houzet L, Defrance P, Droogmans L, Huez G, Kruys V. Tumor necrosis factor-alpha mRNA remains unstable and hypoadenylated upon stimulation of macrophages by lipopolysaccharides.. Eur J Biochem 2000 Oct;267(19):6004-12.
    pubmed: 10998061doi: 10.1046/j.1432-1327.2000.01676.xgoogle scholar: lookup
  97. Maier T, Güell M, Serrano L. Correlation of mRNA and protein in complex biological samples.. FEBS Lett 2009 Dec 17;583(24):3966-73.
    pubmed: 19850042doi: 10.1016/j.febslet.2009.10.036google scholar: lookup
  98. Shebl FM, Pinto LA, García-Piñeres A, Lempicki R, Williams M, Harro C, Hildesheim A. Comparison of mRNA and protein measures of cytokines following vaccination with human papillomavirus-16 L1 virus-like particles.. Cancer Epidemiol Biomarkers Prev 2010 Apr;19(4):978-81.
    pmc: PMC2852493pubmed: 20332253doi: 10.1158/1055-9965.epi-10-0064google scholar: lookup
  99. Koussounadis A, Langdon SP, Um IH, Harrison DJ, Smith VA. Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system.. Sci Rep 2015 Jun 8;5:10775.
    pmc: PMC4459080pubmed: 26053859doi: 10.1038/srep10775google scholar: lookup
  100. Franchini M, Gill U, von Fellenberg R, Bracher VD. Interleukin-8 concentration and neutrophil chemotactic activity in bronchoalveolar lavage fluid of horses with chronic obstructive pulmonary disease following exposure to hay.. Am J Vet Res 2000 Nov;61(11):1369-74.
    pubmed: 11108181doi: 10.2460/ajvr.2000.61.1369google scholar: lookup
  101. Hansen S, Otten ND, Birch K, Skovgaard K, Hopster-Iversen C, Fjeldborg J. Bronchoalveolar lavage fluid cytokine, cytology and IgE allergen in horses with equine asthma.. Vet Immunol Immunopathol 2020 Feb;220:109976.
    pubmed: 31786444doi: 10.1016/j.vetimm.2019.109976google scholar: lookup
  102. Villarete LH, Remick DG. Transcriptional and post-transcriptional regulation of interleukin-8.. Am J Pathol 1996 Nov;149(5):1685-93.
    pmc: PMC1865258pubmed: 8909257
  103. Orlikowsky TW, Neunhoeffer F, Goelz R, Eichner M, Henkel C, Zwirner M, Poets CF. Evaluation of IL-8-concentrations in plasma and lysed EDTA-blood in healthy neonates and those with suspected early onset bacterial infection.. Pediatr Res 2004 Nov;56(5):804-9.
    pubmed: 15319462doi: 10.1203/01.pdr.0000141523.68664.4agoogle scholar: lookup
  104. Baggiolini M, Clark-Lewis I. Interleukin-8, a chemotactic and inflammatory cytokine.. FEBS Lett 1992 Jul 27;307(1):97-101.
    pubmed: 1639201doi: 10.1016/0014-5793(92)80909-zgoogle scholar: lookup
  105. Russo RC, Garcia CC, Teixeira MM, Amaral FA. The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases.. Expert Rev Clin Immunol 2014 May;10(5):593-619.
    pubmed: 24678812doi: 10.1586/1744666x.2014.894886google scholar: lookup
  106. Oglesby IK, Vencken SF, Agrawal R, Gaughan K, Molloy K, Higgins G, McNally P, McElvaney NG, Mall MA, Greene CM. miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production.. Eur Respir J 2015 Nov;46(5):1350-60.
    pubmed: 26160865doi: 10.1183/09031936.00163414google scholar: lookup
  107. Simpson LJ, Patel S, Bhakta NR, Choy DF, Brightbill HD, Ren X, Wang Y, Pua HH, Baumjohann D, Montoya MM, Panduro M, Remedios KA, Huang X, Fahy JV, Arron JR, Woodruff PG, Ansel KM. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production.. Nat Immunol 2014 Dec;15(12):1162-70.
    pmc: PMC4233009pubmed: 25362490doi: 10.1038/ni.3026google scholar: lookup

Citations

This article has been cited 4 times.
  1. Huang S, Li Y, Zeng J, Chang N, Cheng Y, Zhen X, Zhong D, Chen R, Ma G, Wang Y. Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement. Cell Transplant 2023 Jan-Dec;32:9636897231180128.
    doi: 10.1177/09636897231180128pubmed: 37318186google scholar: lookup
  2. Adamič N, Vengust M. Regenerative medicine in lung diseases: A systematic review. Front Vet Sci 2023;10:1115708.
    doi: 10.3389/fvets.2023.1115708pubmed: 36733636google scholar: lookup
  3. Heyman E, Devriendt B, De Vlieghere E, Goethals K, Van Poucke M, Peelman L, De Schauwer C. Evaluation of enzymatic protocols to optimize efficiency of bovine adipose tissue-derived mesenchymal stromal cell isolation. NPJ Sci Food 2024 Oct 1;8(1):70.
    doi: 10.1038/s41538-024-00313-7pubmed: 39353952google scholar: lookup
  4. Moghaddasi K, Hesaraki S, Arfaee F, Athari SS. Investigating the effect of mesenchymal stem cells on the rate of clinical and pathological improvement of asthmatic lung in mouse model. Regen Ther 2024 Mar;25:157-161.
    doi: 10.1016/j.reth.2023.12.013pubmed: 38178929google scholar: lookup
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