The influence of an electromagnetic field on adipose-derived stem/stromal cells’ growth factor secretion: modulation of FGF-2 production by in vitro exposure
Keywords:ASCs, stem cells, growth factors, electromagnetic field, FGF-2
- Proteins secreted by adipose-derived stem/stromal cells have potential use in regenerative medicine.
- Exposure of adipose-derived stem/stromal cells to an electromagnetic field (EMF) (50 Hz; 1.5 mT) in vitro increased the concentrations of pro-regenerative proteins, mostly of basic fibroblast growth factor (FGF-2 protein).
- Exposure to an EMF improved the regenerative potential of adipose-derived stem/stromal cells.
- Cell exposure to an EMF can be used to obtain conditioned media with the cell secretome for regenerative medicine.
Abstract: Adipose-derived stem/stromal cells (ASCs) have tremendous potential for use in regenerative medicine; their secretome is especially important for regenerative processes. We hypothesized that exposure of ASCs to an electromagnetic field (EMF) can influence the proregenerative potential of cells by influencing the secretion of growth factors (GFs) responsible for regenerative properties. We showed that the exposure of ASCs to an EMF (50 Hz; 1.5mT) affected the secretion of GFs as well as the cell cycle process. The most important observation was a statistically significant, 3-fold increase in FGF-2 concentration at 48 h, and a 2-fold decrease at 72 h when compared to the control group. This finding is very important for regenerative medicine, because with precisely adjusted parameters, an EMF can be used to stimulate the production of GFs, mainly of FGF-2, by ASCs, thereby increasing proregenerative properties. The ASC secretome after EMF treatment could be a method for easy, simple and cost-effective stem cell differentiation and therapy facilitation.
Received: March 21, 2020; Revised: May 18, 2020; Accepted: June 15, 2020; Published online: June 23, 2020
How to cite this article: Trzyna A, Pikuła B, Ludwin A, Kocan B, Banaś-Ząbczyk A. The influence of an electromagnetic field on adipose-derived stem/stromal cells’ growth factor secretion: modulation of FGF-2 production by in vitro exposure. Arch Biol Sci. 2020;72(3):339-47.
Markov MS. Electromagnetic Fields and Life. J Electr Electron Syst. 2014;3(1):119.
Redlarski G, Lewczuk B, Żak A, Koncicki A, Krawczuk M, Piechocki J, Jakubiuk K, Tojza P, Jaworski J, Ambroziak D, Skarbek A, Gradolewski D. The influence of electromagnetic pollution on living organisms: Historical trends and forecasting change. Biomed Res Int. 2015;2015:234098.
Gherardini L, Ciuti G, Tognarelli S, Cinti C. Searching for the perfect wave: The effect of radiofrequency electromagnetic fields on cells. Int. J. Mol. Sci. 2014;15(4):5366-87.
Razavi S, Salimi M, Shahbazi-Gahrouei D, Karbasi S, Kermani S. Extremely low-frequency electromagnetic field influences the survival and proliferation effect of human adipose derived stem cells. Adv Biomed Res. 2014;3:25.
Mihai CT, Rotinberg P, Brinza F, Vochita G. Extremely low-frequency electromagnetic fields cause DNA strand breaks in normal cells. J Environ Health Sci Eng. 2014;12(1):15.
Kıvrak EG, Yurt KK, Kaplan AA, Alkan I, Altun G. Effects of electromagnetic fields exposure on the antioxidant defense system. J Microsc Ultrastruct. 2017;5(4):167-176.
Wang H, Zhang X. Magnetic fields and reactive oxygen species. Int J Mol Sci. 2017;18(10):2175.
Maziarz A, Kocan B, Bester M, Budzik S, Cholewa M, Ochiya T, Banas A. How electromagnetic fields can influence adult stem cells: positive and negative impacts. Stem Cell Res Ther. 2016;7(1):54.
Trock DH, Bollet AJ, Markoll R. The effect of pulsed electromagnetic fields in the treatment of osteoarthritis of the knee and cervical spine. Report of randomized, double blind, placebo controlled trials. J Rheumatol. 1994;21(10):1903-11.
Markov MS. How to go to magnetic field therapy? In: Kostarakis P, editor. Proceedings of Second International Workshop of Biological Effects of Electromagnetic Fields;2002 Oct 7-11; Rhodes, Greece. Ioannina, Greece: University of Ioannina; 2002. p. 5-15.
Lin JC. Electromagnetic fields in biological systems. 1st ed. Boca Raton, FL: CRC Press; 2011. p. 171.
Gutin PH, Wong ET. Noninvasive application of alternating electric fields in glioblastoma: a fourth cancer treatment modality. Am Soc Clin Oncol Educ Book. 2012;32:126-31.
Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance therapy with tumor-treating fields plus temozolomidevs temozolomide alone for glioblastoma a randomized clinical trial. JAMA. 2015;314(23):2535-43.
Zimmerman JW, Jimenez H, Pennison MJ, Brezovich I, Morgan D, Mudry A, Costa FP, Barbault A, Pasche B. Targeted treatment of cancer with radiofrequency electromagnetic fields amplitude-modulated at tumor-specific frequencies. Chin J Cancer. 2013;32(11):573-81.
Abou-Saleh H, Zouein FA, El-Yazbi A, Sanoudou D, Raynaud C, Rao C, Pintus G, Dehaini H, Eid AH. The march of pluripotent stem cells in cardiovascular regenerative medicine. Stem Cell Res Ther. 2018;9(1):201.
Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells – current trends and future prospective. Biosci Rep. 2015;35(2):e00191.
Park JE, Seo YK, Yoon HH, Kim CW, Park JK, Jeon S. Electromagnetic fields induce neural differentiation of human bone marrow derived mesenchymal stem cells via ROS mediated EGFR activation. Neurochem Int. 2013;62:418-24.
Parate D, Franco-Obregón A, Fröhlich J, Beyer C, Abbas AA, Kamarul T, Hui JHP, Yang Z. Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields. Sci Rep. 2017;7(1):9421.
Danišovič L, Varga I, Polák S. Growth factors and chondrogenic differentiation of mesenchymal stem cells. Tissue Cell. 2012;44(2):69-73.
Kocan B, Maziarz A, Tabarkiewicz J, Ochiya T, Banaś-Ząbczyk A. Trophic activity and phenotype of adipose tissue-derived mesenchymal stem cells as a background of their regenerative potential. Stem Cells Int. 2017;2017:1653254.
Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kawamata M, Kato T, Okochi H, Ochiya T. IFATS Collection: In vitro therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells. 2008;26:2705-12.
Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9):1852.
Cunningham CJ, Redondo-Castro E, Allan SM. The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke. J Cereb Blood Flow Metab. 2018;38(8):1276-92.
Dubey NK, Mishra VK, Dubey R, Deng YH, Tsai FC, Deng WP. Revisiting the advances in isolation, characterization and secretome of adipose-derived stromal/stem cells. Int J Mol Sci. 2018;19(8):2200.
Van Dongen JA, Harmsen MC, van der Lei B, Stevens HP. Augmentation of dermal wound healing by adipose tissue-derived stromal cells (ASC). Bioengineering. 2018;5(4):91.
Phelps J, Sanati-Nezhad A, Ungrin M, Duncan NA, Sen A. Bioprocessing of mesenchymal stem cells and their derivatives: Toward cell-free therapeutics. Stem Cells Int. 2018;2018:9415367.
Min JK, Lee YM, Kim JH, Kim YM, Kim SW, Lee SY, Gho YS, Oh GT, Kwon YG. Hepatocyte growth factor suppresses vascular endothelial growth factor–Induced expression of endothelial ICAM-1 and VCAM-1 by inhibiting the nuclear factor-ᴋB pathway. Circ Res. 2005;96:300-7.
Mahabeleshwar GH, Byzova TV. Angiogenesis in melanoma. Semin Oncol. 2007;34(6):555-65.
Lopatina T, Favaro E, Grange C, Cedrino M, Ranghino A, Occhipinti S, Fallo S, Buffolo F, Gaykalova DA, Zanone MM, Romagnoli R, Camussi G. PDGF enhances the protective effect of adipose stem cell-derived extracellular vesicles in a model of acute hindlimb ischemia. Sci Rep. 2018;8(1):17458.
Eggenhofer E, Luk F, Dahlke MH, Hoogduijn MJ. The life and fate of mesenchymal stem cells. Front Immunol. 2014;5:148.
Lu Z, Lei D, Jiang T, Yang L, Zheng L, Zhao J. Nerve growth factor from Chinese cobra venom stimulates chondrogenic differentiation of mesenchymal stem cells. Cell Death Dis. 2017;8(5):e2801.
Tamama K, Kawasaki H, Wells A. Epidermal growth factor (EGF) treatment on multipotential stromal cells (MSCs). Possible enhancement of therapeutic potential of MSC. J Biomed Biotechnol. 2010;2010:795385.
Lim S, Cho H, Lee E, Won Y, Kim C, Ahn W, Lee E, Son Y. (2016), Osteogenic stimulation of human adipose-derived stem cells by pre-treatment with fibroblast growth factor 2, Cell Tissue Res. 2016;364(1):137-47.
Cherepkova MY, Sineva GS, Pospelov VA. Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway. Cell Death Dis. 2016;7(1):e2050.
McLean K, Tan L, Bolland DE, Coffman LG, Peterson LF, Talpaz M, Neamati N, Buckanovich RJ. Leukemia inhibitory factor functions in parallel with interleukin-6 to promote ovarian cancer growth. Oncogene. 2019;38(9):1576-84.
Prior M, Goldberg J, Chiruta C, Farrokhi C, Kopynets M, Roberts AJ, Schubert D. Selecting for neurogenic potential as an alternative for Alzheimer's disease drug discovery. Alzheimers Dement. 2016;12(6):678-86.
Nawrocka D, Kornicka K, Szydlarska J, Marycz K. Basic fibroblast growth factor inhibits apoptosis and promotes proliferation of adipose-derived mesenchymal stromal cells isolated from patients with type 2 diabetes by reducing cellular oxidative stress. Oxid Med Cell Longev. 2017;2017:3027109.
Zhang C, Guo H, Yang C, Chen Q, Huang J, Liu L, Zhang Y, Jin S, Song A, Yang P. The biological behavior optimization of human periodontal ligament stem cells via preconditioning by the combined application of fibroblast growth factor-2 and A83-01 in in vitro culture expansion. J Transl Med. 2019;17(1):66.
Pizzute T, Li J, Zhang Y, Davis ME, Pei M. Fibroblast growth factor ligand dependent proliferation and chondrogenic differentiation of synovium-derived stem cells and concomitant adaptation of Wnt/mitogen-activated protein kinase signals. Tissue Eng Part A. 2016;22(15-16):1036-46.
Aizman I, Vinodkumar D, McGrogan M, Bates D. Cell injury-induced release of fibroblast growth factor 2: Relevance to intracerebral mesenchymal stromal cell transplantations. Stem Cells Dev. 2015;24(14):1623-34.
Woodbury ME, Ikezu T. Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration. J Neuroimmune Pharmacol.. 2014;9(2):92-101.
Harfouche G, Vaigot P, Rachidi W, Rigaud O, Moratille S, Marie M, Lemaitre G, Fortunel NO, Martin MT. Fibroblast growth factor type 2 signaling is critical for DNA repair in human keratinocyte stem cells. Stem Cells. 2010;28(9):1639-48.
Ross CL, Siriwardane M, Almeida-Porada G, Porada CD, Brink P, Christ GJ, Harrison BS. The effect of low-frequency electromagnetic field on human bone marrow stem/progenitor cell differentiation. Stem Cell Res. 2015;15(1):96-108.
Blaber SP, Webster RA, Hill CJ, Breen EJ, Kuah D, Vesey G, Herbert BR. Analysis of in vitro secretion profiles from adipose-derived cell populations. J Transl Med. 2012;10:172.
Jadidi M, Biat SM, Sameni HR, Safari M, Vafaei AA, Ghahari L. Mesenchymal stem cells that located in the electromagnetic fields improves rat model of Parkinson's disease. Iran J Basic Med Sci. 2016;19(7):741-8.
Gessi S, Merighi, S, Bencivenni S, Battistello E, Vincenzi F, Setti S, Cadossi M, Borea PA, Cadossi R, Varani K. Pulsed electromagnetic field and relief of hypoxia-induced neuronal cell death: The signaling pathway. J Cell Physiol. 2019;234:15089-97.
Oladnabi M, Bagheri A, Rezaei Kanavi M, Azadmehr A, Kianmehr A. Extremely low frequency-pulsed electromagnetic fields affect proangiogenic-related gene expression in retinal pigment epithelial cells. Iran J Basic Med Sci. 2019;22(2):128-33.
Fan W, Qian F, Ma Q, Zhang P, Chen T, Chen C, Zhang Y, Deng P, Zhou Z, Yu Z. 50 Hz electromagnetic field exposure promotes proliferation and cytokine production of bone marrow mesenchymal stem cells. Int J Clin Exp Med. 2015;8(5):7394-404.
Jeong WY, Kim JB, Kim HJ, Kim CW. Extremely low-frequency electromagnetic field promotes astrocytic differentiation of human bone marrow mesenchymal stem cells by modulating SIRT1 expression. Biosci Biotechnol Biochem. 2017;81:1356-62.
Garza-Veloz I, Romero-Diaz VJ, Martinez-Fierro ML, Marino-Martinez IA, Gonzalez-Rodriguez M, Martinez-Rodriguez HG, Espinoza-Juarez MA, Bernal-Garza DA, Ortiz-Lopez R, Rojas-Martinez A. Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer. Arthritis Res Ther. 2013;15(4):R80.
Weiss S, Hennig T, Bock R, Steck E, Richter W. Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J. Cell. Physiol. 2010;223(1):84-93.
Correa D, Somoza RA, Lin P, Greenberg S, Rom E, Duesler L, Welter JF, Yayon A, Caplan AI. Sequential exposure to fibroblast growth factors (FGF) 2, 9 and 18 enhances hMSC chondrogenic differentiation. Osteoarthritis Cartilage. 2015;23(3):443-53.
Nasrabadi D, Rezaeiani S, Eslaminejad MB, Shabani A. Improved protocol for chondrogenic differentiation of bone marrow derived mesenchymal stem cells -Effect of PTHrP and FGF-2on TGFβ1/BMP2-induced chondrocytes hypertrophy. Stem Cell Rev Rep. 2018;14(5):755-66.
Jeong CH, Kim SM, Lim JY, Ryu CH, Jun JA, Jeun SS. Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance endogenous neurogenesis in an ischemic stroke model. Biomed Res Int. 2014;2014:129145.
Steringer JP, Lange S, Čujová S, Šachl R, Poojari C, Lolicato F, Beutel O, Müller HM, Unger S, Coskun Ü, Honigmann A, Vattulainen I, Hof M, Freund C, Nickel W. Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components. Elife. 2017;6:e28985.
Zhang, M., Li, X., Bai, L. Uchida K, Bai W, Wu B, Xu W, Zhu H, Huang H. Effects of low frequency electromagnetic field on proliferation of human epidermal stem cells: an in vitro study. Bioelectromagnetics. 2013;34(1):74-80.
Tepper OM, Callaghan MJ, Chang EI, Galiano RD, Bhatt KA, Baharestani S, Gan J, Simon B, Hopper RA, Levine JP, Gurtner GC. Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of FGF-2. FASEB J. 2004;18(11):1231-3.
Callaghan MJ, Chang EI, Seiser N, Aarabi S, Ghali S, Kinnucan ER, Simon BJ, Gurtner GC. Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release. Plast Reconstr Surg. 2008;121(1):130-41.
D'Angelo C, Costantini E, Kamal MA, Reale M. Experimental model for ELF-EMF exposure: Concern for human health. Saudi J Biol Sci. 2015;22(1):75-84.