Vitamin E and hCG enhance the immunomodulatory properties of LPS-induced mesenchymal stem/stromal cells

Iranian Journal of Veterinary Science and Technology

مقاله 8، دوره 13، شماره 1 - شماره پیاپی 24، شهریور 2021، صفحه 64-74   

نوع مقاله: Research Article

شناسه دیجیتال (DOI): 10.22067/ijvst.2021.68338.1010

نویسندگان

Sepideh sadat Hosseini¹؛ Shadi Mehrzad¹؛ Halimeh Hassanzadeh²؛ Mahboubeh Kazemi³؛ Nasser Sanjar moussavi⁴؛ Madjid Momeni Moghaddam⁵؛ Hamid Reza Bidkhori^{* 6}؛ Moein Farshchian^{* 6}

¹Stem Cells and Regenerative Medicine Research Department, Academic Center for Education, Culture, and Research (ACECR)-Khorasan Razavi, Mashhad, Iran.

²Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi, University campus, Azadi sq., Mashhad, Iran & Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

³Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

⁴Department of Surgery, Faculty of Medicine, Islamic Azad University-Mashhad Branch, Mashhad, Iran.

⁵Department of Biology, Faculty of Science, Hakim Sabzevari University, Sabzevar, Iran.

⁶Stem Cells and Regenerative Medicine Research Department, Academic Center for Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran.

چکیده

Mesenchymal Stem/Stromal Cells (MSCs) have been applied to modulate various immune-mediated conditions. Prolonged culture of MSCs in vitro reduces their therapeutic efficacy. Pretreatment of the cells with some chemical agents during in vitro expansion could overcome this limitation. This study intended to determine whether pretreatment of adipose-derived MSCs (ASCs) with Human chorionic gonadotrophin (hCG), a glycoprotein hormone, and Vitamin E, an antioxidant, will improve their immunomodulatory ability. In this regard, ASCs were harvested from human processed lipoaspirate. LPS-induced ASCs were preconditioned with 1 mg of hCG and 600 µM of vitamin E for 24h. TSG-6, COX-2, IL-1β, and IL-6 were assessed at the mRNA level in preconditioned and control groups. ASCs were also co-cultured with peripheral blood mononuclear cells (PBMCs) in vitro to determine the functionality of these cells. Results showed that hCG and vitamin E significantly downregulate the pro-inflammatory COX-2, IL-1β, and IL-6 gene expression, while they did not significantly increase TSG-6 expression. Besides, the co-culturing of pretreated ASCs with PBMCs demonstrated that the amount of PBMCs in treated groups (with hCG and vitamin E) was significantly lower than in control groups. These findings revealed that the preconditioning of ASCs with hCG and vitamin E might enhance their immunoregulatory capacity.

کلیدواژه‌ها

hCG؛ Immune regulation؛ ASCs؛ pretreatment؛ stem cells؛ Vitamin E

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مراجع

1. Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Molecular therapy : the journal of the American Society of Gene Therapy. 2012; Jan;20(1):14-20.
2. Mastrolia I, Foppiani EM, Murgia A, Candini O, Samarelli AV, Grisendi G, et al. Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review. Stem cells translational medicine. 2019; Nov;8(11):1135-48.
3. Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y. Immunobiology of mesenchymal stem cells. Cell death and differentiation. 2014; Feb;21(2):216-25.
4. Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfusion Medicine and Hemotherapy. 2016; 43(4):268-74.
5. Kim J, Kang JW, Park JH, Choi Y, Choi KS, Park KD, et al. Biological characterization of long-term cultured human mesenchymal stem cells. Archives of pharmacal research. 2009; 32(1):117-26.
6. Antebi B, Mohammadipoor A, Batchinsky AI, Cancio LC. The promise of mesenchymal stem cell therapy for acute respiratory distress syndrome. Journal of Trauma and Acute Care Surgery. 2018; 84(1):183-91.
7. Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell stem cell. 2018; 22(6):824-33.
8. Schaefer R, Spohn G, Baer PC. Mesenchymal stem/stromal cells in regenerative medicine: can preconditioning strategies improve therapeutic efficacy. Transfusion Medicine and Hemotherapy. 2016; 43(4):256-67.
9. Saeedi P, Halabian R, Fooladi AAI. A revealing review of mesenchymal stem cells therapy, clinical perspectives and modification Stem Cell Investig. 2019; 6:34.
10. Tang J, Xiong J, Wu T, Tang Z, Ding G, Zhang C, et al. Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPARγ/TGF-β1 pathway. Stem cells and development. 2014; 23(17):2093-103.
11. Mehmood A, Wajid N, Rauf M, Khan SN, Riazuddin S. Vitamin E protects chondrocytes against hydrogen peroxide-induced oxidative stress in vitro. Inflammation Research. 2013; 62(8):781-9.
12. Linares GR, Chiu C-T, Scheuing L, Leng Y, Liao H-M, Maric D, et al. Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease. Experimental neurology. 2016; 281:81-92.
13. Oses C, Olivares B, Ezquer M, Acosta C, Bosch P, Donoso M, et al. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy. PLoS One. 2017; 12(5):e0178011.
14. An J-H, Li Q, Bhang D-H, Song W-J, Youn H-Y. TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis. Scientific reports. 2020; 10(1):1-14.
15. Cromer A, Zuniga M, Cohen D, Smith JR, Weiss M. Modulation of human umbilical cord-derived mesenchymal stromal cells immunophenotype through cellular priming. The FASEB Journal. 2017; 31(1_supplement):lb504-lb.
16. de Cássia Noronha N, Mizukami A, Caliári-Oliveira C, Cominal JG, Rocha JLM, Covas DT, et al. Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies. Stem cell research & therapy. 2019; 10(1):131.
17. Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science. 1922 1922/12//;56(1458):650-1.
18. Azzi A. Many tocopherols, one vitamin E. Molecular aspects of medicine. 2018; 61:92-103.
19. Zingg J-M, Meydani M. Interaction Between Vitamin E and Polyunsaturated Fatty Acids. Vitamin E in Human Health: Springer; 2019. p. 141-59.
20. Mahoney CW, Azzi A. Vitamin E inhibits protein kinase C activity. Biochemical and Biophysical Research Communications. 1988; 154(2):694-7.
21. Zingg J-M. Vitamin E: a role in signal transduction. Annual review of nutrition. 2015; 35:135-73.
22. Lee GY, Han SN. The role of vitamin E in immunity. Nutrients. 2018; 10(11):1614.
23. Wu D, Meydani SN. Vitamin E, Immune Function, and Protection Against Infection. Vitamin E in Human Health: Springer; 2019. p. 371-84.
24. Biswas SK. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxidative medicine and cellular longevity. 2016: 5698931.
25. Elbeltagy MAF, Elkholy WB, Salman AS. Effect of atherosclerosis and the protective effect of the antioxidant vitamin E on the rabbit cerebellum. Microscopy. 2019; 68(5):369-78.
26. Alshiek JA, Dayan L, Asleh R, Blum S, Levy AP, Jacob G. Anti-oxidative treatment with vitamin E improves peripheral vascular function in patients with diabetes mellitus and Haptoglobin 2-2 genotype: A double-blinded cross-over study. Diabetes Research and Clinical Practice. 2017; 131:200-7.
27. Bansal AS, Bora SA, Saso S, Smith JR, Johnson MR, Thum M-Y. Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy. Expert Review of Clinical Immunology. 2012; 8(8):747-53.
28. De A, Sachdeva R, Bose A, Malik M, Jayachandran N, Pal R. Human Chorionic Gonadotropin influences systemic autoimmune responses. Frontiers in Endocrinology. 2018; 9:742.
29. van Groenendael R, Beunders R, Kox M, van Eijk LT, Pickkers P, editors. The Human Chorionic Gonadotropin Derivate EA-230 Modulates the Immune Response and Exerts Renal Protective Properties: Therapeutic Potential in Humans. Seminars in Nephrology; 2019: Elsevier.
30. Huang X, Cai Y, Ding M, Zheng B, Sun H, Zhou J. Human chorionic gonadotropin promotes recruitment of regulatory T cells in endometrium by inducing chemokine CCL2. Journal of Reproductive Immunology. 2020; 137:102856.
31. Sauss K, Ehrentraut S, Zenclussen AC, Schumacher A. The pregnancy hormone human chorionic gonadotropin differentially regulates plasmacytoid and myeloid blood dendritic cell subsets. American Journal of Reproductive Immunology. 2018; 79(4):e12837.
32. Theofanakis C, Drakakis P, Besharat A, Loutradis D. Human chorionic gonadotropin: the pregnancy hormone and more. International journal of molecular sciences. 2017; 18(5):1059.
33. Fuchs T, Hammarström L, Smith CI, Brundin J. In vitro induction of murine suppressor T-cells by human chorionic gonadotropin. Acta obstetricia et gynecologica Scandinavica. 1980; 59(4):355-9.
34. Rao CV. Potential Therapy for Rheumatoid Arthritis and Sjögren Syndrome With Human Chorionic Gonadotropin. Reproductive sciences (Thousand Oaks, Calif). 2016 May;23(5):566-71.
35. Cismaru AC, Soritau O, Jurj AM, Raduly L-Z, Pop B, Bocean C, et al. Human Chorionic Gonadotropin Improves the Proliferation and Regenerative Potential of Bone Marrow Adherent Stem Cells and the Immune Tolerance of Fetal Microchimeric Stem Cells In Vitro. Stem Cell Reviews and Reports. 2020: 1-17.
36. van Groenendael R, Aarnoutse R, Kox M, van Eijk L, Pickkers P. Pharmacokinetics, safety and tolerability of the novel β‐hCG derived immunomodulatory compound, EA‐230. British journal of clinical pharmacology. 2019; 85(7):1572-84.
37. van den Berg HR, Khan NA, van der Zee M, Bonthuis F, IJzermans JN, Dik WA, et al. Synthetic oligopeptides related to the β-subunit of human chorionic gonadotropin attenuate inflammation and liver damage after (trauma) hemorrhagic shock and resuscitation. Shock. 2009; 31(3):285-91.
38. Pramanik A, Das S, Khanna GL. Differential effects of performance-enhancing drugs ‘Methamphetamine’and ‘hCG’on ex-vivo cultured primary blood mononuclear cells of male athletes. Pharmacological Reports. 2020: 1-11.
39. Bai H, Pan J, Jia X. The inhibition effect of human chorionic gonadotropin (hCG) on mRNA expression of cytokines initiated inflammatory reaction. Chinese Journal of Immunology. 1985 (03).
40. sadat Hosseini S, Mehrzad S, Hassanzadeh H, Bidkhori HR, Mirahmadi M, Momeni-Moghaddam M, et al. Immunosuppressive Effects of Human Chorionic Gonadotropin (hCG) on Mesenchymal Stromal Cells. Journal of Cell and Molecular Research. 2020; 11(2):90-98.
41. Mehrzad S, sadat Hosseini S, Momeni-Moghaddam M, Farshchian M, Hassanzadeh H, Mirahmadi M, et al. Vitamin E Pretreatment of Mesenchymal Stem Cells: The Interplay of Oxidative Stress and Inflammation. 2020; 11(2):99-107.
42. Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell death & disease. 2016 Jan 21;7:e2062.
43. Shall G, Menosky M, Decker S, Nethala P, Welchko R, Leveque X, et al. Effects of passage number and differentiation protocol on the generation of dopaminergic neurons from rat bone marrow-derived mesenchymal stem cells. International journal of molecular sciences. 2018; 19(3):720.
44. Avery MB, Belanger BL, Bromley A, Sen A, Mitha AP. Mesenchymal Stem Cells Exhibit Both a Proinflammatory and Anti-Inflammatory Effect on Saccular Aneurysm Formation in a Rabbit Model. Stem cells international. 2019; 2019.
45. Zhong W, Tong Y, Li Y, Yuan J, Hu S, Hu T, et al. Mesenchymal stem cells in inflammatory microenvironment potently promote metastatic growth of cholangiocarcinoma via activating Akt/NF-κB signaling by paracrine CCL5. Oncotarget. 2017; 8(43):73693.
46. Baer PC, Overath JM, Urbschat A, Schubert R, Koch B, Bohn AA, et al. Effect of different preconditioning regimens on the expression profile of murine adipose-derived stromal/stem cells. International journal of molecular sciences. 2018; 19(6):1719.
47. Noronha NC, Mizukami A, Caliari-Oliveira C, Cominal JG, Rocha JLM, Covas DT, et al. Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies. Stem Cell Res Ther. 2019 May 2; 10(1):131.
48. 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 Apr 26; 5(4):e10088.
49. Najar M, Krayem M, Meuleman N, Bron D, Lagneaux L. Mesenchymal stromal cells and toll-like receptor priming: a critical review. Immune network. 2017; 17(2):89-102.
50. Jahandideh S, Khatami S, Eslami Far A, Kadivar M. Anti-inflammatory effects of human embryonic stem cell-derived mesenchymal stem cells secretome preconditioned with diazoxide, trimetazidine and MG-132 on LPS-induced systemic inflammation mouse model. Artificial cells, nanomedicine, and biotechnology. 2018; 46(sup2):1178-87.
51. Somensi N, Rabelo TK, Guimarães AG, Quintans-Junior LJ, de Souza Araújo AA, Moreira JCF, et al. Carvacrol suppresses LPS-induced pro-inflammatory activation in RAW 264.7 macrophages through ERK1/2 and NF-kB pathway. International immunopharmacology. 2019; 75:105743.
52. Day AJ, Milner CM. TSG-6: A multifunctional protein with anti-inflammatory and tissue-protective properties. Matrix Biology. 2019; 78:60-83.
53. Roddy GW, Oh JY, Lee RH, Bartosh TJ, Ylostalo J, Coble K, et al. Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6. Stem cells (Dayton, Ohio). 2011 Oct; 29(10):1572-9.
54. Schaper F, Rose-John S. Interleukin-6: biology, signaling and strategies of blockade. Cytokine & growth factor reviews. 2015; 26(5):475-87.
55. Kumari N, Dwarakanath B, Das A, Bhatt AN. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumor Biology. 2016; 37(9):11553-72.
56. Nakata K, Hanai T, Take Y, Osada T, Tsuchiya T, Shima D, et al. Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: a systematic review. Osteoarthritis and cartilage. 2018; 26(10):1263-73.
57. Mirshafiey A, Taeb M, Mortazavi-Jahromi SS, Jafarnezhad-Ansariha F, Rehm BH, Esposito E, et al. Introduction of β-d-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression. Pharmacological reports. 2017; 69(5):1067-72.
58. Morrovati F, Fathi NK, Rad JS, Montaseri A. Mummy Prevents IL-1β-Induced Inflammatory Responses and Cartilage Matrix Degradation via Inhibition of NF-қB Subunits Gene Expression in Pellet Culture System. Advanced pharmaceutical bulletin. 2018; 8(2):283.
59. Spohn G, Arenas-Ramirez N, Bouchaud G, Boyman O. Endogenous polyclonal anti–IL-1 antibody responses potentiate IL-1 activity during pathogenic inflammation. Journal of Allergy and Clinical Immunology. 2017; 139(6):1957-65. e3.
60. Zhu J, Bing C, Wilding JP. 1α, 25 (OH) 2 D 3 attenuates IL-6 and IL-1β-mediated inflammatory responses in macrophage conditioned medium-stimulated human white preadipocytes by modulating p44/42 MAPK and NF-κB signaling pathways. Diabetology & metabolic syndrome. 2019; 11(1):9.
61. Li B, Jones LL, Geiger TL. IL-6 promotes T cell proliferation and expansion under inflammatory conditions in association with low-level RORγt expression. The Journal of Immunology. 2018; 201(10):2934-46.