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Veterinary medicine and science2021; 7(3); 626-633; doi: 10.1002/vms3.427

The effect of equine bone marrow-derived mesenchymal stem cells on the expression of apoptotic genes in neutrophils.

Abstract: Bone marrow mesenchymal stem cells (BM-MSCs), as multipotent cells with self-renewal and plastic-adherent properties, have immunomodulatory effects on immune cells, including neutrophils. These cells are in close proximity in bone marrow (BM) sinusoids with non-multiplicative immature neutrophils. BM-MSCs exert their immunomodulatory effects on adjacent cells both directly (cell-to-cell contact) and indirectly (secretion of soluble factors). The aim of this study was to evaluate the effect of equine bone marrow mesenchymal stem cells (BM-MSCs) on the expression of some pro- and anti-apoptotic genes (p53, survivin and Bcl ) in neutrophils co-cultured with BM-MSCs. For this purpose, peripheral blood neutrophils were isolated and separately co-cultured for 12 hr with both BM-MSCs and the BM-MSCs΄ supernatant. Four groups were included: neutrophils with only culture media (as control), neutrophils co-cultured with BM-MScs, neutrophils cultured with BM-MSCs' supernatant and neutrophils cultured with lipopolysaccharide (LPS, as positive control). Then, the expression of mentioned genes (p53, survivin and Bcl ) was evaluated by quantitative polymerase chain reaction (qPCR). Compared with control neutrophils, in neutrophils co-cultured with both BM-MSCs and BM-MSCs' supernatant, the mRNA expression levels of p53, as pro-apoptotic gene, and survivin and Bcl , as anti-apoptotic genes, were remarkably increased and decreased (p < .05), respectively. These data revealed the notion that the direct contact of BM-MSCs is not obligatory for their effects on the apoptotic status of neutrophils and they affect neutrophils via soluble secreted factors, which is promising for clinical implications in equine medicine.
© 2021 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.
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Publication Date: 2021-01-20 PubMed ID: 33471967PubMed Central: PMC8136922DOI: 10.1002/vms3.427Google Scholar: Lookup
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  • 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.

This research study looked into how equine bone marrow mesenchymal stem cells (BM-MSCs) affect the expression of certain apoptosis-related genes in neutrophils. It specifically studied the potency of the stem cells both through direct contact and via secreted soluble factors, providing insights valuable for equine medicine.

Research Background and Objective

  • The study focuses on bone marrow mesenchymal stem cells (BM-MSCs), specifically from horses (equine). These stem cells are multipotent, meaning they can develop into different kinds of cells, and have the capacity to renew themselves.
  • BM-MSCs are known for their immunomodulatory effects on immune cells, particularly neutrophils. Neutrophils are a type of white blood cell that play a vital role in the body’s immune response.
  • The aim was to determine how the equine BM-MSCs impact the expression of some apoptosis-related genes in neutrophils. Apoptosis is the natural, programmed death of cells, and its regulation is important for maintaining health.

Experimental Procedures

  • To study this, the researchers isolated peripheral blood neutrophils and co-cultured them either directly with BM-MSCs or with the soluble factors released by these BM-MSCs (their supernatant).
  • There were four experimental groups: neutrophils with only culture media (as a control), neutrophils co-cultured with BM-MSCs, neutrophils cultured with the BM-MSCs’ supernatant, and neutrophils cultured with lipopolysaccharide (LPS, a substance used as a positive control).
  • They then measured the levels of mRNAs for a pro-apoptotic gene (p53) and two anti-apoptotic genes (survivin and Bcl) using quantitative polymerase chain reaction (qPCR).

Research Findings

  • The researchers discovered that, compared with the control neutrophils, those co-cultured with both the BM-MSCs and the BM-MSCs’ supernatant showed significant changes in gene expression.
  • The levels of mRNA for the p53 gene, which promotes apoptosis, were markedly increased. In contrast, the levels of mRNA for the survivin and Bcl genes, which inhibit apoptosis, were notably decreased.
  • These results suggest that direct contact with the BM-MSCs is not necessary for their effects on apoptosis to be manifested in neutrophils. Instead, the soluble secreted factors from these stem cells are enough to exert an effect.

Conclusion

  • This study concludes that BM-MSCs significantly affect apoptosis in neutrophils, not just through direct cell-to-cell contact but also via soluble factors they secreted.
  • This observation can have important implications for equine medicine, particularly in further understanding the immunomodulatory effects of stem cells and how they could be harnessed for health benefits.

Cite This Article

APA
Salami F, Ghodrati M, Parham A, Mehrzad J. (2021). The effect of equine bone marrow-derived mesenchymal stem cells on the expression of apoptotic genes in neutrophils. Vet Med Sci, 7(3), 626-633. https://doi.org/10.1002/vms3.427

Publication

Veterinary medicine and science
ISSN: 2053-1095
NlmUniqueID: 101678837
Country: England
Language: English
Volume: 7
Issue: 3
Pages: 626-633

Researcher Affiliations

Salami, Fatemeh
  • Division of Physiology, Department of Basic Sciences, Veterinary Faculty, Ferdowsi University of Mashhad, Mashhad, Iran.
Ghodrati, Mitra
  • Division of Physiology, Department of Basic Sciences, Veterinary Faculty, Ferdowsi University of Mashhad, Mashhad, Iran.
Parham, Abbas
  • Division of Physiology, Department of Basic Sciences, Veterinary Faculty, Ferdowsi University of Mashhad, Mashhad, Iran.
  • Stem Cell Biology and Regenerative Medicine Research Group, Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Mehrzad, Jalil
  • Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

MeSH Terms

  • Animals
  • Apoptosis / genetics
  • Bone Marrow
  • Female
  • Gene Expression Regulation, Developmental
  • Horses
  • Mesenchymal Stem Cells / metabolism
  • Neutrophils / metabolism

References

This article includes 42 references
  1. Alipour F, Parham A, Kazemi Mehrjerdi H, Dehghani H. Equine adipose-derived mesenchymal stem cells: phenotype and growth characteristics, gene expression profile and differentiation potentials.. Cell J 2015 Winter;16(4):456-65.
    pmc: PMC4297484pubmed: 25685736doi: 10.22074/cellj.2015.491google scholar: lookup
  2. Allen PD, Bustin SA, Newland AC. The role of apoptosis (programmed cell death) in haemopoiesis and the immune system.. Blood Rev 1993 Mar;7(1):63-73.
    doi: 10.1016/0268-960X(93)90025-Ypubmed: 8467234google scholar: lookup
  3. Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy.. Trends Mol Med 2001 Dec;7(12):542-7.
    pubmed: 11733216doi: 10.1016/s1471-4914(01)02243-2google scholar: lookup
  4. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.. Nat Med 1997 Aug;3(8):917-21.
    doi: 10.1038/nm0897-917pubmed: 9256286google scholar: lookup
  5. Berkow RL, Dodson RW. Purification and functional evaluation of mature neutrophils from human bone marrow.. Blood 1986 Oct;68(4):853-60.
    doi: 10.1182/blood.V68.4.853.853pubmed: 3019453google scholar: lookup
  6. Bianco P, Gehron Robey P. Marrow stromal stem cells.. J Clin Invest 2000 Jun;105(12):1663-8.
    doi: 10.1172/JCI10413pmc: PMC378520pubmed: 10862779google scholar: lookup
  7. Brach MA, deVos S, Gruss HJ, Herrmann F. Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death.. Blood 1992 Dec 1;80(11):2920-4.
    doi: 10.1182/blood.V80.11.2920.2920pubmed: 1280481google scholar: lookup
  8. Brandau S, Jakob M, Hemeda H, Bruderek K, Janeschik S, Bootz F, Lang S. Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge.. J Leukoc Biol 2010 Nov;88(5):1005-15.
    doi: 10.1189/jlb.0410207pubmed: 20682625google scholar: lookup
  9. Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products.. Blood 1992 Oct 15;80(8):2012-20.
    doi: 10.1182/blood.V80.8.2012.bloodjournal8082012pubmed: 1382715google scholar: lookup
  10. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A. Human mesenchymal stem cells modulate B-cell functions.. Blood 2006 Jan 1;107(1):367-72.
    pubmed: 16141348doi: 10.1182/blood-2005-07-2657google scholar: lookup
  11. Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses.. Exp Hematol 2000 Aug;28(8):875-84.
    pubmed: 10989188doi: 10.1016/s0301-472x(00)00482-3google scholar: lookup
  12. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.. Blood 2002 May 15;99(10):3838-43.
    pubmed: 11986244doi: 10.1182/blood.v99.10.3838google scholar: lookup
  13. el-Deiry WS. Regulation of p53 downstream genes.. Semin Cancer Biol 1998;8(5):345-57.
    doi: 10.1006/scbi.1998.0097pubmed: 10101800google scholar: lookup
  14. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F, Romagnani P, Maggi E, Romagnani S, Annunziato F. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells.. Stem Cells 2006 Feb;24(2):386-98.
    doi: 10.1634/stemcells.2005-0008pubmed: 16123384google scholar: lookup
  15. Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S. Secretion of immunoregulatory cytokines by mesenchymal stem cells.. World J Stem Cells 2014 Nov 26;6(5):552-70.
    doi: 10.4252/wjsc.v6.i5.552pmc: PMC4178255pubmed: 25426252google scholar: lookup
  16. Lee A, Whyte MK, Haslett C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators.. J Leukoc Biol 1993 Oct;54(4):283-8.
    doi: 10.1002/jlb.54.4.283pubmed: 8409750google scholar: lookup
  17. Liles WC, Kiener PA, Ledbetter JA, Aruffo A, Klebanoff SJ. Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils.. J Exp Med 1996 Aug 1;184(2):429-40.
    doi: 10.1084/jem.184.2.429pmc: PMC2192712pubmed: 8760796google scholar: lookup
  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
    doi: 10.1006/meth.2001.1262pubmed: 11846609google scholar: lookup
  19. Ma XL, Tsao PS, Viehman GE, Lefer AM. Neutrophil-mediated vasoconstriction and endothelial dysfunction in low-flow perfusion-reperfused cat coronary artery.. Circ Res 1991 Jul;69(1):95-106.
    doi: 10.1161/01.RES.69.1.95pubmed: 2054945google scholar: lookup
  20. Maqbool M, Vidyadaran S, George E, Ramasamy R. Human mesenchymal stem cells protect neutrophils from serum-deprived cell death.. Cell Biol Int 2011 Dec;35(12):1247-51.
    doi: 10.1042/CBI20110070pubmed: 21649586google scholar: lookup
  21. Mehrzad J, Devriendt B, Baert K, Cox E. Aflatoxin B₁ interferes with the antigen-presenting capacity of porcine dendritic cells.. Toxicol In Vitro 2014 Jun;28(4):531-7.
    doi: 10.1016/j.tiv.2013.11.015pubmed: 24389110google scholar: lookup
  22. Mehrzad J, Duchateau L, Burvenich C. Phagocytic and bactericidal activity of blood and milk-resident neutrophils against Staphylococcus aureus in primiparous and multiparous cows during early lactation.. Vet Microbiol 2009 Feb 16;134(1-2):106-12.
    pubmed: 18954946doi: 10.1016/j.vetmic.2008.09.001google scholar: lookup
  23. Mehrzad J, Klein G, Kamphues J, Wolf P, Grabowski N, Schuberth HJ. In vitro effects of very low levels of aflatoxin B₁ on free radicals production and bactericidal activity of bovine blood neutrophils.. Vet Immunol Immunopathol 2011 May 15;141(1-2):16-25.
    doi: 10.1016/j.vetimm.2011.01.010pubmed: 21377741google scholar: lookup
  24. Mehrzad J, Maleki M, Raji A, Razmi G. An ultrastructural investigation of the blood neutrophils in camel (Camelus dromedarius). Comparative Clinical Pathology 23(4), 885–892.
    doi: 10.1007/s00580-013-1707-7google scholar: lookup
  25. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.. Oncogene 1994 Jun;9(6):1799-805.
    pubmed: 8183579
  26. Moulding DA, Quayle JA, Hart CA, Edwards SW. Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival.. Blood 1998 Oct 1;92(7):2495-502.
    doi: 10.1182/blood.V92.7.2495.2495_2495_2502pubmed: 9746790google scholar: lookup
  27. Nemeth K, Mezey E. Bone marrow stromal cells as immunomodulators. A primer for dermatologists.. J Dermatol Sci 2015 Jan;77(1):11-20.
    doi: 10.1016/j.jdermsci.2014.10.004pmc: PMC4294767pubmed: 25476233google scholar: lookup
  28. Opferman JT, Kothari A. Anti-apoptotic BCL-2 family members in development.. Cell Death Differ 2018 Jan;25(1):37-45.
    doi: 10.1038/cdd.2017.170pmc: PMC5729530pubmed: 29099482google scholar: lookup
  29. Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F, Ottonello L, Pistoia V. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche.. Stem Cells 2008 Jan;26(1):151-62.
    doi: 10.1634/stemcells.2007-0416pubmed: 17932421google scholar: lookup
  30. Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F. Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle.. Transplantation 2007 Jan 15;83(1):71-6.
    doi: 10.1097/01.tp.0000244572.24780.54pubmed: 17220794google scholar: lookup
  31. Rasmusson I. Immune modulation by mesenchymal stem cells.. Exp Cell Res 2006 Jul 15;312(12):2169-79.
    doi: 10.1016/j.yexcr.2006.03.019pubmed: 16631737google scholar: lookup
  32. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide.. Cell Stem Cell 2008 Feb 7;2(2):141-50.
    doi: 10.1016/j.stem.2007.11.014pubmed: 18371435google scholar: lookup
  33. Salami F, Tavassoli A, Mehrzad J, Parham A. Immunomodulatory effects of mesenchymal stem cells on leukocytes with emphasis on neutrophils.. Immunobiology 2018 Dec;223(12):786-791.
    doi: 10.1016/j.imbio.2018.08.002pubmed: 30119931google scholar: lookup
  34. Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: clearance of apoptotic cells regulates immune responses.. Nat Rev Immunol 2002 Dec;2(12):965-75.
    doi: 10.1038/nri957pubmed: 12461569google scholar: lookup
  35. Sax JK, El-Deiry WS. p53 downstream targets and chemosensitivity.. Cell Death Differ 2003 Apr;10(4):413-7.
    doi: 10.1038/sj.cdd.4401227pubmed: 12719718google scholar: lookup
  36. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method.. Nat Protoc 2008;3(6):1101-8.
    doi: 10.1038/nprot.2008.73pubmed: 18546601google scholar: lookup
  37. Silva MT, Correia-Neves M. Neutrophils and macrophages: the main partners of phagocyte cell systems.. Front Immunol 2012;3:174.
    doi: 10.3389/fimmu.2012.00174pmc: PMC3389340pubmed: 22783254google scholar: lookup
  38. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2.. Blood 2008 Feb 1;111(3):1327-33.
    doi: 10.1182/blood-2007-02-074997pubmed: 17951526google scholar: lookup
  39. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs.. Cancer Res 1998 Dec 1;58(23):5315-20.
    pubmed: 9850056
  40. Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B. Identification and classification of p53-regulated genes.. Proc Natl Acad Sci U S A 1999 Dec 7;96(25):14517-22.
    doi: 10.1073/pnas.96.25.14517pmc: PMC24468pubmed: 10588737google scholar: lookup
  41. Zahedi M, Parham A, Dehghani H, Mehrjerdi HK. Stemness Signature of Equine Marrow-derived Mesenchymal Stem Cells.. Int J Stem Cells 2017 May 30;10(1):93-102.
    doi: 10.15283/ijsc16036pmc: PMC5488781pubmed: 28222255google scholar: lookup
  42. Zhang Q, Shi S, Liu Y, Uyanne J, Shi Y, Shi S, Le AD. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis.. J Immunol 2009 Dec 15;183(12):7787-98.
    doi: 10.4049/jimmunol.0902318pmc: PMC2881945pubmed: 19923445google scholar: lookup

Citations

This article has been cited 2 times.
  1. Abatay-Sel F, Erol A, Suleymanoglu M, Demirayak G, Kekik-Cinar C, Kuruca DS, Savran-Oguz F. The in vitro treatment of mesenchymal stem cells for colorectal cancer cells. Med Oncol 2023 Feb 22;40(3):103.
    doi: 10.1007/s12032-023-01972-4pubmed: 36811793google scholar: lookup
  2. Salinas-Varas C, Espinosa G, Muñoz-Caro T, Conejeros I, Gärtner U, Fey K, Arnhold S, Taubert A, Hermosilla C. Equine adipose-derived stem cells modulate in vitro neutrophil extracellular trap release by polymorphonuclear neutrophils. Front Vet Sci 2025;12:1685757.
    doi: 10.3389/fvets.2025.1685757pubmed: 41200546google scholar: lookup
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