The Effect of Hypoxia on the Soluble Molecules of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs)
Effect of hypoxia on MSCs secretome
Keywords:
UC-MSCs, hypoxia, secretome, wound healing, survival
Abstract
Background: Umbilical cord-derived stem cells (UC-MSCs) are essential cell sources for cell-based therapies in regenerative medicine. Hypoxia is a key element of the stem cell niche and crucial for the preservation of UC-MSCs properties. The normal growth conditions for UC-MSCs are under atmospheric oxygen concentrations of 20–21%. However, the administration of UC-MSCs in inflammatory conditions provides oxygen-deficient environments. Thus, treating UC-MSCs with low oxygen exposure provides them with more survival and recovery potential.
Objective: In this study, we assessed the impact of hypoxia incubation for 12 h on the UC-MSCs proteome.
Methods: UC-MSCs were isolated from UC patients regarding informed consent. At passage 5, in 80% confluent, UC-MSCs were incubated in 5% O2 for 12 h. The morphology of UC-MSCs was assessed using a microscope. The level of FGF-2, FGF-8, TNF-α, and HSP-70 were analyzed using ELISA.
Results: Hypoxic condition could change their morphology and enhance the cellular density compared to normoxic conditions in vitro. The level of FGF-2, FGF-8, TNF-α, and HSP-70 were significantly increased after the hypoxic condition of UC-MSCs compared to normoxia.
Conclusion: Our findings suggest that the hypoxic condition was able to induce survival capacity and soluble molecules secreted by UC-MSCs.
References
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2. Restimulia L, Ilyas S, Munir D, Putra A, Madiadipoera T, Farhat F, Sembiring RJ, Ichwan M, Amalina ND, Alif I. The CD4+CD25+FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis. Med Arch. 2021;75(4):256-261.
3. Nie, C. et al. Locally administered adipose-derived stem cells accelerate wound healing through diferentiation and vasculogenesis. Cell Transplant. 20, 205–216.
4. Strong, A. L. et al. Characterization of a murine pressure ulcer model to assess efcacy of adipose-derived stromal cells. Plast. Reconstr. Surg. Glob.Open 3, e334.
5. Ebrahimian, T. G. et al. Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing. Arterioscler. Tromb. Vasc. Biol. 29, 503–510
6. Rehman, J. et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109, 1292–1298.
7. Linero, I. & Chaparro, O. Paracrine efect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS ONE 9, e107001
8. Yustianingsih V, Sumarawati T, Putra A. Hypoxia enhances self-renewal properties and markers of mesenchymal stem cells. Univ Med [Internet]. 2019;38(3):164-71.
9. Nugraha A, Putra A. Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats. Univ Med. 2018;37(2):135-42.
10. Putra A, Widyatmoko A, Ibrahim S, Amansyah F, Amansyah F, Berlian MA, Retnaningsih R, Pasongka Z, Sari FE, Rachmad B. Case series of the first three severe COVID-19 patients treated with the secretome of hypoxia-mesenchymal stem cells in Indonesia. F1000Res. 2021;10:228.
11. Frazier, T. P., Gimble, J. M., Kheterpal, I. & Rowan, B. G. Impact of low oxygen on the secretome of human adipose-derived stromal/ stem cell primary cultures. Biochimie 95, 2286–2296.
12. Nekanti U, Dastidar S, Venugopal P, Totey S, Ta M. Increased proliferation and analysis of differential gene expression in human Wharton's jelly-derived mesenchymal stromal cells under hypoxia. Int J Biol Sci. 2010;6:499–512.
13. Saller MM, Prall WC, Docheva D, Schonitzer V, Popov T, Anz D, et al. Increased stemness and migration of human mesenchymal stem cells in hypoxia is associated with altered integrin expression. Biochem Biophys Res Commun. 2012;423:379–85
14. Cicione C, Muinos-Lopez E, Hermida-Gomez T, Fuentes-Boquete I, Diaz-Prado S, Blanco FJ. Effects of severe hypoxia on bone marrow mesenchymal stem cells differentiation potential. Stem Cells Int. 2013;2013:232896.
15. Holzwarth C, Vaegler M, Gieseke F, Pfister SM, Handgretinger R, Kerst G, et al. Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells. BMC Cell Biol. 2010;11:11.
16. Lavrentieva A, Majore I, Kasper C, Hass R. Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells. Cell Commun Signal. 2010;8:18
17. Basciano L, Nemos C, Foliguet B, de Isla N, de Carvalho M, Tran N, et al. Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status. BMC Cell Biol. 2011;12:12.
18. Putra A, Riwanto I, Putra ST, Wijaya I. Typhonium flagelliforme extract induce apoptosis in breast cancer stem cells by suppressing survivin. J Cancer Res Ther. 2020;16(6):1302-1308.
19. Putra A, Tjahjono T, Winarto W. Efektivitas Ekstrak Umbi Typhonium flagelliforme Fraksi Diklorometanolik dalam Menghambat Proliferasi Sel MCF-7 Kanker Payudara. J Indon Med Assoc. 2012;62(1):10-15.
20. Nylandsted, J., Gyrd-Hansen, M., Danielewicz, A., Fehrenbacher, N., Lademann, U., Høyer-Hansen, M., Weber, E., Multhoff, G., Rohde, M., & Jäättelä, M. (2004). Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. The Journal of experimental medicine, 200(4), 425–435.
21. Otsuka T, Mengsteab PY, Laurencin CT. Control of mesenchymal cell fate via application of FGF-8b in vitro. Stem Cell Res. 2021;51:102155.
22. Mossahebi-Mohammadi M, Quan M, Zhang JS, Li X. FGF Signaling Pathway: A Key Regulator of Stem Cell Pluripotency. Front Cell Dev Biol. 2020;8:79.
23. Farooq M, Khan AW, Kim MS, Choi S. The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration. Cells. 2021;10(11):3242.
24. Popko K, Gorska E, Stelmaszczyk-Emmel A, Plywaczewski R, Stoklosa A, Gorecka D, Pyrzak B, Demkow U. Proinflammatory cytokines Il-6 and TNF-α and the development of inflammation in obese subjects. Eur J Med Res. 2010;15 Suppl 2(Suppl 2):120-2.
25. Selvasandran K, Makhoul G, Jaiswal PK, Jurakhan R, Li L, Ridwan K, Cecere R. A Tumor Necrosis Factor-α and Hypoxia-Induced Secretome Therapy for Myocardial Repair. Ann Thorac Surg. 2018 Mar;105(3):715-723.
Published
2023-01-31
How to Cite
Widyatmoko, A., Alif, I., Irawan, R. C. S., Handoyo, F. E., & Sidiq, H. A. (2023). The Effect of Hypoxia on the Soluble Molecules of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs). International Journal of Cell and Biomedical Science, 1(3), 102-108. https://doi.org/10.59278/cbs.v1i3.24
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