Priming of Mesenchymal Stem Cells for Enhanced Interleukin-10 Secretion via Conditioned Medium from Lipopolysaccharide-Activated Peripheral Blood Mononuclear Cells
Abstract
Background: Mesenchymal stem cells (MSCs) are known for their immunomodulatory properties, particularly their ability to secrete anti-inflammatory cytokines such as interleukin-10 (IL-10). Enhancing the secretion of IL-10 by MSCs could have significant therapeutic potential for treating inflammatory diseases. Objective: This study aimed to prime the secretion of IL-10 by MSCs through the use of conditioned medium (CM) derived from lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMCs). Methods: MSCs were isolated from Wharton’s Jelly and characterized using flow cytometry and differentiation assays. PBMCs were isolated from human blood samples and stimulated with LPS to produce a pro-inflammatory environment. The conditioned medium from these LPS-induced PBMCs was collected and add to MSCs culture medium in 5% and 7.5%. After 24h and 48h incubation, IL-10 secretion by MSCs was measured using an enzyme-linked immunosorbent assay (ELISA). Results: The results demonstrated that MSCs cultured in the conditioned medium from LPS-induced PBMCs showed a significant increase in IL-10 secretion compared to control conditions in 24h exposure, but not significantly different in 48h. Conclusion: The exposure of conditioned medium from LPS-induced PBMCs may effectively enhances the secretion of IL-10 by MSCs.
References
Ellis S, Lin EJ, Tartar D. Immunology of Wound Healing. Published online 2018:350-358.
Rasouli M, Naeimzadeh Y, Hashemi N, Hosseinzadeh S. Age-Related Alterations in Mesenchymal Stem Cell Function: Understanding Mechanisms and Seeking Opportunities to Bypass the Cellular Aging. Curr Stem Cell Res Ther. 2024;19(1):15-32. doi:10.2174/1574888X18666230113144016
Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol. Published online 2018. doi:10.3389/fimmu.2018.00754
Udalamaththa VL, Kaluarachchi A, Wijeratne S, Udagama PV. Therapeutic uses of post-partum tissue-derived mesenchymal stromal cell secretome. Indian J Med Res. 2020;152(6):541. doi:10.4103/IJMR.IJMR_1450_18
Ormazabal V, Nova-Lampeti E, Rojas D, et al. Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model. Int J Mol Sci. 2022;23(2):1-13. doi:10.3390/ijms23020941
Al-Azzawi B, McGuigan DH, Koivula FNM, et al. The Secretome of Mesenchymal Stem Cells Prevents Islet Beta Cell Apoptosis via an IL-10-Dependent Mechanism. Open Stem Cell J. 2020;6(1):1-12. doi:10.2174/1876893802006010001
Zhao X, Zhao Y, Sun X, Xing Y, Wang X, Yang Q. Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis. Front Bioeng Biotechnol. 2020;8(October):1-14. doi:10.3389/fbioe.2020.575057
Deo D, Marchioni M, Rao P. Mesenchymal Stem/Stromal Cells in Organ Transplantation. Pharmaceutics. Published online 2022. doi:10.3390/pharmaceutics14040791
Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol. 2019;10(JUN):1-10. doi:10.3389/fimmu.2019.01191
Yang Y, Wu Y, Yang D, et al. Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles. Bioact Mater. 2023;27(October 2022):98-112. doi:10.1016/j.bioactmat.2023.03.017
Katagiri W, Watanabe J, Toyama N, Osugi M, Sakaguchi K, Hibi H. Clinical Study of Bone Regeneration by Conditioned Medium from Mesenchymal Stem Cells after Maxillary Sinus Floor Elevation. Implant Dent. 2017;26(4):607-612. doi:10.1097/ID.0000000000000618
Gunawardena TNA, Rahman MT, Abdullah BJJ, Kasim NHA. Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine. J Tissue Eng Regen Med. 2019;13(4):569-586. doi:10.1002/TERM.2806
Ueha S, Shand FHW, Matsushima K. Cellular and molecular mechanisms of chronic inflammation-associated organ fibrosis. Front Immunol. 2012;3(APR):1-6. doi:10.3389/fimmu.2012.00071
Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. Published online 2019. doi:10.3390/ijms20236008
Dyer D. TSG-6 inhibits neutrophil migration via direct interaction with the chemokine CXCL8. J Immunol. 2014;192(5):2177-2185. doi:10.4049/jimmunol.1300194
M M, E C, M N, et al. Pro-inflammatory M1/Th1 type immune network and increased expression of TSG-6 in the eutopic endometrium from women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2017;218:99-105. doi:10.1016/J.EJOGRB.2017.08.014
Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177-185. doi:10.1038/nature21363
Wang X, Coradin T, Hélary C. Modulating inflammation in a cutaneous chronic wound model by IL-10 released from collagen-silica nanocomposites: Via gene delivery. Biomater Sci. 2018;6(2):398-406. doi:10.1039/c7bm01024a
Song J young, Kang HJ, Ju HM, et al. Umbilical cord-derived mesenchymal stem cell extracts ameliorate atopic dermatitis in mice by reducing the T cell responses. Sci Rep. 2019;9(1):1-9. doi:10.1038/s41598-019-42964-7
Mühl H, Dhingra S, Booz GW, et al. IL-10/STAT3/SOCS3 Axis Is Involved in the Anti-inflammatory Effect of Benznidazole. Front Immunol | www.frontiersin.org. 2019;1:1267. doi:10.3389/fimmu.2019.01267
Pham K, Parikh K, Heinrich EC. Hypoxia and Inflammation: Insights From High-Altitude Physiology. Front Physiol. 2021;12(May). doi:10.3389/fphys.2021.676782
Putra A, Ridwan FB, Putridewi AI, et al. The Role of TNF-α Induced MSCs on Suppressive Inflammation.pdf. 2018;6(10):1779-1783.
Petrenko Y, Vackova I, Kekulova K, et al. A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential. Sci Reports 2020 101. 2020;10(1):1-15. doi:10.1038/s41598-020-61167-z
Thitilertdecha P, Lohsiriwat V, Poungpairoj P, Tantithavorn V, Onlamoon N. Extensive Characterization of Mesenchymal Stem Cell Marker Expression on Freshly Isolated and in Vitro Expanded Human Adipose-Derived Stem Cells from Breast Cancer Patients. Stem Cells Int. 2020;2020. doi:10.1155/2020/8237197
Schachtele S, Clouser C, Aho J. Methods to Validate Mesenchymal Stem Cell Identity, Potency, and Quality. R&D Syst. Published online 2018.
Zhou T, Li HY, Liao C, Lin W, Lin S. Clinical Efficacy and Safety of Mesenchymal Stem Cells for Systemic Lupus Erythematosus. Stem Cells Int. 2020;2020. doi:10.1155/2020/6518508
Madrigal M, Rao KS, Riordan NH. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med. 2014;12(1):1-14. doi:10.1186/s12967-014-0260-8
Sargent A, Miller RH. MSC Therapeutics in Chronic Inflammation. Curr Stem Cell Reports. 2016;2(2):168-173. doi:10.1007/s40778-016-0044-6
Sari MI, Jusuf NK, Munir D, et al. The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis. Biomedicines. Published online 2023. doi:10.3390/biomedicines11082325
Uberti B, Plaza A, Henríquez C. Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species. Front Vet Sci. 2022;9:806069. doi:10.3389/FVETS.2022.806069
Kurte M, Vega-Letter AM, Luz-Crawford P, et al. Time-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAE. Stem Cell Res Ther. 2020;11(1):1-14. doi:10.1186/s13287-020-01840-2
Mazgaeen L, Gurung P. Recent Advances in Lipopolysaccharide Recognition Systems. Published online 2020.
Herzig MC, Christy BA, Montgomery RK, et al. Interactions of human mesenchymal stromal cells with peripheral blood mononuclear cells in a Mitogenic proliferation assay. J Immunol Methods. 2021;492:113000. doi:10.1016/J.JIM.2021.113000
Nugraha A, Putra A. Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats. Universa Med. 2018;37(2):135. doi:10.18051/univmed.2018.v37.135-142
Gao F, Chiu SM, Motan DAL, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis. 2016;7(1). doi:10.1038/cddis.2015.327
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