Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture, Conditioned Medium Preparation and UCMSC-EVs Isolation
2.2. Measurement of EVs Size and Concentration Distribution with Nanoparticle Tracking Analysis (NTA)
2.3. Transmission Electron Microscopy (TEM)
2.4. Reactive Oxygen Species (ROS) Measurement
2.5. Cytokine Measurement
2.6. Western Blot Analysis
2.7. Degranulation Assay
2.8. Statistical Analysis
3. Results
3.1. Physiochemical Properties of UCMSC-EVs
3.2. Viability of KU812 Cells under UCMSC-EVs Treatment
3.3. UCMSC-EVs Attenuated IE-Induced ROS Generation and Degranulation in KU812 Cells
3.4. UCMSC-EVs Exposure Decreases the Production of Multiple Proinflammatory Cytokines in KU812 Cells
3.5. UCMSC-EVs Inhibited Inflammatory and Allergic Reactions by Suppressing the NF-kB and MAPK Signaling Pathways
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Gurung, S.; Perocheau, D.; Touramanidou, L.; Baruteau, J. The exosome journey: From biogenesis to uptake and intracellular signalling. Cell Commun. Signal. 2021, 19, 47. [Google Scholar] [CrossRef]
- Silva, A.K.A.; Morille, M.; Piffoux, M.; Arumugam, S.; Mauduit, P.; Larghero, J.; Bianchi, A.; Aubertin, K.; Blanc-Brude, O.; Noël, D.; et al. Development of extracellular vesicle-based medicinal products: A position paper of the group “Extracellular Vesicle translatiOn to clinicaL perspectiVEs–EVOLVE France”. Adv. Drug Deliv. Rev. 2021, 179, 114001. [Google Scholar] [CrossRef]
- Doyle, L.M.; Wang, M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 2019, 8, 727. [Google Scholar] [CrossRef] [Green Version]
- Lötvall, J.; Hill, A.F.; Hochberg, F.; Buzás, E.I.; Di Vizio, D.; Gardiner, C.; Gho, Y.S.; Kurochkin, I.V.; Mathivanan, S.; Quesenberry, P.; et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles 2014, 3, 26913. [Google Scholar] [CrossRef]
- Nikfarjam, S.; Rezaie, J.; Zolbanin, N.M.; Jafari, R. Mesenchymal stem cell derived-exosomes: A modern approach in translational medicine. J. Transl. Med. 2020, 18, 449. [Google Scholar] [CrossRef]
- Wang, W.M.; Wu, C.; Jin, H.Z. Exosomes in chronic inflammatory skin diseases and skin tumors. Exp. Dermatol. 2019, 28, 213–218. [Google Scholar] [CrossRef]
- Yang, G.H.; Lee, Y.B.; Kang, D.; Choi, E.; Nam, Y.; Lee, K.H.; You, H.-J.; Kang, H.J.; An, S.H.; Jeon, H. Overcome the barriers of the skin: Exosome therapy. Biomater. Res. 2021, 25, 22. [Google Scholar] [CrossRef]
- Shafei, S.; Khanmohammadi, M.; Heidari, R.; Ghanbari, H.; Taghdiri Nooshabadi, V.; Farzamfar, S.; Akbariqomi, M.; Sanikhani, N.S.; Absalan, M.; Tavoosidana, G. Exosome loaded alginate hydrogel promotes tissue regeneration in full-thickness skin wounds: An in vivo study. J. Biomed. Mater. Res. Part A 2020, 108, 545–556. [Google Scholar] [CrossRef]
- Bai, Y.; Yan, X.L.; Ren, J.; Zeng, Q.; Li, X.D.; Pei, X.T.; Han, Y. Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury. Biochem. Biophys. Res. Commun. 2018, 500, 310–317. [Google Scholar] [CrossRef]
- Wang, L.; Hu, L.; Zhou, X.; Xiong, Z.; Zhang, C.; Shehada, H.; Hu, B.; Song, J.; Chen, L. Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling. Sci. Rep. 2017, 7, 13321. [Google Scholar] [CrossRef]
- Hu, S.; Li, Z.; Cores, J.; Huang, K.; Su, T.; Dinh, P.U.; Cheng, K. Needle-free injection of exosomes derived from human dermal fibroblast spheroids ameliorates skin photoaging. ACS Nano 2019, 13, 11273–11282. [Google Scholar] [CrossRef]
- Shang, F.; Liu, S.; Ming, L.; Tian, R.; Jin, F.; Ding, Y.; Zhang, Y.; Zhang, H.; Deng, Z.; Jin, Y. Human Umbilical Cord MSCs as New Cell Sources for Promoting Periodontal Regeneration in Inflammatory Periodontal Defect. Theranostics 2017, 7, 4370–4382. [Google Scholar] [CrossRef]
- Shi, Y.; Wang, Y.; Li, Q.; Liu, K.; Hou, J.; Shao, C.; Wang, Y. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat. Rev. Nephrol. 2018, 14, 493–507. [Google Scholar] [CrossRef]
- Andaloussi, S.E.L.; Mäger, I.; Breakefield, X.O.; Wood, M.J. Extracellular vesicles: Biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 2013, 12, 347–357. [Google Scholar] [CrossRef]
- Li, T.; Xia, M.; Gao, Y.; Chen, Y.; Xu, Y. Human umbilical cord mesenchymal stem cells: An overview of their potential in cell-based therapy. Expert Opin. Biol. Ther. 2015, 15, 1293–1306. [Google Scholar] [CrossRef]
- Zhang, K.; Yu, L.; Li, F.-R.; Li, X.; Wang, Z.; Zou, X.; Zhang, C.; Lv, K.; Zhou, B.; Mitragotri, S.; et al. Topical Application of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Combination with Sponge Spicules for Treatment of Photoaging. Int. J. Nanomed. 2020, 15, 2859–2872. [Google Scholar] [CrossRef] [Green Version]
- Fan, C.-G.; Zhang, Q.-J.; Zhou, J.-R. Therapeutic Potentials of Mesenchymal Stem Cells Derived from Human Umbilical Cord. Stem Cell Rev. Rep. 2011, 7, 195–207. [Google Scholar] [CrossRef]
- Haraszti, R.A.; Miller, R.; Stoppato, M.; Sere, Y.Y.; Coles, A.; Didiot, M.C.; Wollacott, R.; Sapp, E.; Dubuke, M.L.; Li, X.; et al. Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity. Mol. Ther. 2018, 26, 2838–2847. [Google Scholar] [CrossRef] [Green Version]
- Zipkin, M.J.N.B. Exosome redux. Nat. Biotechnol. 2019, 37, 1395–1400. [Google Scholar] [CrossRef]
- Krystel-Whittemore, M.; Dileepan, K.N.; Wood, J.G. Mast Cell: A Multi-Functional Master Cell. Front. Immunol. 2015, 6, 620. [Google Scholar] [CrossRef] [PubMed]
- Paivandy, A.; Pejler, G. Novel Strategies to Target Mast Cells in Disease. J. Innate Immun. 2021, 13, 131–147. [Google Scholar] [CrossRef]
- Ando, T.; Xiao, W.; Gao, P.; Namiranian, S.; Matsumoto, K.; Tomimori, Y.; Hong, H.; Yamashita, H.; Kimura, M.; Kashiwakura, J.-I.; et al. Critical Role for Mast Cell Stat5 Activity in Skin Inflammation. Cell Rep. 2014, 6, 366–376. [Google Scholar] [CrossRef] [Green Version]
- Shelburne, C.P.; McCoy, M.E.; Piekorz, R.; Sexl, V.; Roh, K.-H.; Jacobs-Helber, S.M.; Gillespie, S.R.; Bailey, D.P.; Mirmonsef, P.; Mann, M.N.; et al. Stat5 expression is critical for mast cell development and survival. Blood 2003, 102, 1290–1297. [Google Scholar] [CrossRef] [Green Version]
- Kimata, M.; Inagaki, N.; Kato, T.; Miura, T.; Serizawa, I.; Nagai, H. Roles of mitogen-activated protein kinase pathways for mediator release from human cultured mast cells. Biochem. Pharmacol. 2000, 60, 589–594. [Google Scholar] [CrossRef]
- Popović, M.; de Marco, A. Canonical and selective approaches in exosome purification and their implications for diagnostic accuracy. Transl. Cancer Res. 2018, 7, S209–S225. [Google Scholar] [CrossRef]
- Lyons, J.J.; Yi, T. Mast cell tryptases in allergic inflammation and immediate hypersensitivity. Curr. Opin. Immunol. 2021, 72, 94–106. [Google Scholar] [CrossRef]
- Wang, D.; Na, Q.; Song, G.Y.; Wang, L. Human umbilical cord mesenchymal stem cell-derived exosome-mediated transfer of microRNA-133b boosts trophoblast cell proliferation, migration and invasion in preeclampsia by restricting SGK1. Cell Cycle 2020, 19, 1869–1883. [Google Scholar] [CrossRef]
- Faruqu, F.N.; Liam-Or, R.; Zhou, S.; Nip, R.; Al-Jamal, K.T. Defined serum-free three-dimensional culture of umbilical cord-derived mesenchymal stem cells yields exosomes that promote fibroblast proliferation and migration in vitro. FASEB J. 2021, 35, e21206. [Google Scholar] [CrossRef]
- Elieh Ali Komi, D.; Wöhrl, S.; Bielory, L. Mast Cell Biology at Molecular Level: A Comprehensive Review. Clin. Rev. Allergy Immunol. 2020, 58, 342–365. [Google Scholar] [CrossRef]
- Galli, S.J.; Tsai, M. IgE and mast cells in allergic disease. Nat. Med. 2012, 18, 693–704. [Google Scholar] [CrossRef]
- Kamran, M.; Liang, J.; Liu, B.; Li, Y.; Gao, J.; Keating, A.; Mohamed, F.; Dai, S.; Reinhardt, R.; Jiong, Y.; et al. The Clusters of Transcription Factors NFATC2, STAT5, GATA2, AP1, RUNX1 and EGR2 Binding Sites at the Induced Il13 Enhancers Mediate Il13 Gene Transcription in Response to Antigenic Stimulation. J. Immunol. 2020, 205, 3311–3318. [Google Scholar] [CrossRef]
- Forrester, S.J.; Kikuchi, D.S.; Hernandes, M.S.; Xu, Q.; Griendling, K.K. Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ. Res. 2018, 122, 877–902. [Google Scholar] [CrossRef]
- Kazeroonian, A.; Theis, F.J.; Hasenauer, J. A scalable moment-closure approximation for large-scale biochemical reaction networks. Bioinformatics 2017, 33, i293–i300. [Google Scholar] [CrossRef] [Green Version]
- Yan, C.; Ying, J.; Lu, W.; Changzhi, Y.; Qihong, Q.; Jingzhu, M.; Dongjie, S.; Tingting, Z. MiR-1294 suppresses ROS-dependent inflammatory response in atopic dermatitis via restraining STAT3/NF-κB pathway. Cell. Immunol. 2022, 371, 104452. [Google Scholar] [CrossRef]
- Cho, B.S.; Kim, J.O.; Ha, D.H.; Yi, Y.W. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res. Ther. 2018, 9, 187. [Google Scholar] [CrossRef]
IgE | |||||
---|---|---|---|---|---|
pg/mL | Control | 107 | 108 | 109 | |
IL-6 | 15.01 ± 1.12 | 41.66 ± 1.03 b | 26.23 ± 0.26 e | 20.44 ± 0.34 e | 24.04 ± 1.29 d |
TNF-α | 14.08 ± 0.56 | 24.02 ± 0.32 b | 14.48 ± 0.16 e | 13.46 ± 0.32 e | 14.85 ± 0.24 e |
IL-β | 145.10 ± 0.24 | 237.77 ± 11.73 a | 167.03 ± 4.74 e | 146.41 ± 8.36 d | 154.19 ± 22.26 c |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lin, T.-Y.; Chang, T.-M.; Huang, H.-C. Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation. Antioxidants 2022, 11, 2279. https://doi.org/10.3390/antiox11112279
Lin T-Y, Chang T-M, Huang H-C. Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation. Antioxidants. 2022; 11(11):2279. https://doi.org/10.3390/antiox11112279
Chicago/Turabian StyleLin, Tzou-Yien, Tsong-Min Chang, and Huey-Chun Huang. 2022. "Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation" Antioxidants 11, no. 11: 2279. https://doi.org/10.3390/antiox11112279