eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 14
Basic research

Effects of single and combined low frequency electromagnetic fields and simulated microgravity on gene expression of human mesenchymal stem cells during chondrogenesis

Susanne Mayer-Wagner, Florian Hammerschmid, Helmut Blum, Stefan Krebs, Julia I. Redeker, Boris M. Holzapfel, Volkmar Jansson, Peter E. Müller

Arch Med Sci 2018; 14, 3: 608–616
Online publish date: 2016/05/16
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Low frequency electromagnetic fields (LF-EMF) and simulated microgravity (SMG) have been observed to affect chondrogenesis. A controlled bioreactor system was developed to apply LF-EMF and SMG singly or combined during chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in 3D culture.

Material and methods
An external motor gear SMG bioreactor was combined with magnetic Helmholtz coils for EMF (5 mT; 15 Hz). Pellets of hMSCs (±TGF-3) were cultured (P5) under SMG, LF-EMF, LF-EMF/SMG and control (1 g) conditions for 3 weeks. Sections were stained with safranin-O and collagen type II. Gene expression was evaluated by microarray and real-time polymerase chain reaction analysis.

Simulated microgravity application significantly changed gene expression; specifically, COLXA1 but also COL2A1, which represents the chondrogenic potential, were reduced (p < 0.05). Low frequency electromagnetic fields application showed no gene expression changes on a microarray basis. LF-EMF/SMG application obtained significant different expression values from cultures obtained under SMG conditions with a re-increase of COL2A1, therefore rescuing the chondrogenic potential, which had been lowered by SMG.

Simulated microgravity lowered hypertrophy but also the chondrogenic potential of hMSCs. Combined LF-EMF/SMG provided a rescue effect of the chondrogenic potential of hMSCs although no LF-EMF effect was observed under optimal conditions. The study provides new insights into how LF-EMF and SMG affect chondrogenesis of hMSCs and how they generate interdependent effects.


bioreactor, electromagnetic fields, simulated microgravity, chondrogenesis

Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 2002; 10: 432-63.
Czyżewska A, Glinkowski WM, Walesiak K, Krawczak K, Cabaj D, Górecki A. Effects of preoperative physiotherapy in hip osteoarthritis patients awaiting total hip replacement. Arch Med Sci 2014; 10: 985-91.
Madeira C, Santhagunam A, Salgueiro JB, Cabral JM. Advanced cell therapies for articular cartilage regeneration. Trends Biotechnol 2015; 33: 35-42.
Chen S, Fu P, Cong R, Wu H, Pei M. Strategies to minimize hypertrophy in cartilage engineering and regeneration. Genes Dis 2015; 2 276-95.
Blaber E, Marcal H, Burns BP. Bioastronautics: the influence of microgravity on astronaut health. Astrobiology 2010; 10: 463-73.
Carmeliet G, Nys G, Stockmans I, Bouillon R. Gene expression related to the differentiation of osteoblastic cells is altered by microgravity. Bone 1998; 22: 139S-43S.
Landis WJ, Hodgens KJ, Block D, Toma CD, Gersten-feld LC. Spaceflight effects on cultured embryonic chick bone cells. J Bone Mineral Res 2000; 15: 1099-112.
Rucci N, Migliaccio S, Zani BM, Taranta A, Teti A. Characterization of the osteoblast-like cell phenotype under microgravity conditions in the NASA-approved rotating wall vessel bioreactor (RWV). J Cell Biochem 2002; 85: 167-79.
Mayer-Wagner S, Hammerschmid F, Redeker JI, et al.Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells. Int Orthop 2014.
Duke J, Daane E, Arizpe J, Montufar-Solis D. Chondrogenesis in aggregates of embryonic limb cells grown in a rotating wall vessel. Adv Space Res 1996; 17: 289-93.
Stamenkovic V, Keller G, Nesic D, Cogoli A, Grogan SP. Neocartilage formation in 1 g, simulated, and microgravity environments: implications for tissue engineering. Tissue Eng A 2010; 16: 1729-36.
Sheyn D, Pelled G, Netanely D, Domany E, Gazit D. The effect of simulated microgravity on human mesenchymal stem cells cultured in an osteogenic differentiation system: a bioinformatics study. Tissue Eng A 2010; 16: 3403-12.
Fini M, Pagani S, Giavaresi G, et al. Functional tissue engineering in articular cartilage repair: is there a role for electromagnetic biophysical stimulation? Tissue Eng B Rev 2013; 19: 353-67.
Ross CL, Siriwardane M, Almeida-Porada G, et al. The effect of low-frequency electromagnetic field on human bone marrow stem/progenitor cell differentiation. Stem Cell Res 2015; 15: 96-108.
Mayer-Wagner S, Passberger A, Sievers B, et al. Effects of low frequency electromagnetic fields on the chondrogenic differentiation of human mesenchymal stem cells. Bioelectromagnetics 2011; 32: 283-90.
Li S, Yu B, Zhou D, He C, Zhuo Q, Hulme JM. Electromagnetic fields for treating osteoarthritis. Cochrane Database Syst Rev 2013; 12: CD003523.
Balamuralikrishnan B, Balachandar V, Kumar SS, et al. Evaluation of chromosomal alteration in electrical workers occupationally exposed to low frequency of electromagnetic field (EMFs) in Coimbatore population, India. APJCP 2012; 13: 2961-6.
Kirschenlohr H, Ellis P, Hesketh R, Metcalfe J. Gene expression profiles in white blood cells of volunteers exposed to a 50 Hz electromagnetic field. Radiation Res 2012; 178: 138-49.
Berg-Beckhoff G, Breckenkamp J, Larsen PV, Kowall B. General practitioners’ knowledge and concern about electromagnetic fields. Int J Environ Res Public Health 2014; 11: 12969-82.
Mueller MB, Tuan RS. Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells. Arthritis Rheumat 2008; 58: 1377-88.
Wagner S, Hofstetter W, Chiquet M, et al. Early osteoarthritic changes of human femoral head cartilage subsequent to femoro-acetabular impingement. Osteoarthritis Cartilage 2003; 11: 508-18.
Kauffmann A, Gentleman R, Huber W. arrayQualityMetrics: a bioconductor package for quality assessment of microarray data. Bioinformatics 2009; 25: 415-6.
Vandesompele J, De Preter K, Pattyn F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3: RESEARCH0034.
Varas L, Ohlsson LB, Honeth G, et al. alpha10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential. Stem Cells Develop 2007; 16: 965-78.
Zhang LM, Su PQ, Xu CX, Yang JL, Yu WH, Huang DS. Chondrogenic differentiation of human mesenchymal stem cells: a comparison between micromass and pellet culture systems. Biotechnol Lett 2010; 32: 1339-46.
Bassen H, Litovitz T, Penafiel M, Meister R. ELF in vitro exposure systems for inducing uniform electric and magnetic fields in cell culture media. Bioelectromagnetics 1992; 13: 183-98.
Rambaut PC, Johnston RS. Prolonged weightlessness and calcium loss in man. Acta Astronautica 1979; 6: 1113-22.
Kumei Y, Shimokawa H, Katano H, et al. Microgravity induces prostaglandin E2 and interleukin-6 production in normal rat osteoblasts: role in bone demineralization. J Biotechnol 1996; 47: 313-24.
Ohyabu Y, Kida N, Kojima H, Taguchi T, Tanaka J, Uemura T. Cartilaginous tissue formation from bone marrow cells using rotating wall vessel (RWV) bioreactor. Biotechnol Bioeng 2006; 95: 1003-8.
Freed LE, Langer R, Martin I, Pellis NR, Vunjak-Novakovic G. Tissue engineering of cartilage in space. Proc Natl Acad Sci USA 1997; 94: 13885-90.
Veronesi F, Torricelli P, Giavaresi G, et al. In vivo effect of two different pulsed electromagnetic field frequencies on osteoarthritis. J Orthop Res 2014; 32: 677-85.
Fini M, Torricelli P, Giavaresi G, et al. Effect of pulsed electromagnetic field stimulation on knee cartilage, subchondral and epyphiseal trabecular bone of aged Dunkin Hartley guinea pigs. Biomed Pharmacother 2008; 62: 709-15.
Ciombor DM, Aaron RK, Wang S, Simon B. Modification of osteoarthritis by pulsed electromagnetic field: a morphological study. Osteoarthritis Cartilage 2003; 11: 455-62.
Ongaro A, Pellati A, Setti S, et al. Electromagnetic fields counteract IL-1beta activity during chondrogenesis of bovine mesenchymal stem cells. J Tissue Eng Regen Med 2015; 9: E229-38.
Aaron RK, Boyan BD, Ciombor DM, Schwartz Z, Simon BJ. Stimulation of growth factor synthesis by electric and electromagnetic fields. Clin Orthop Relat Res 2004; 419: 30-7.
Doucet IL. Biological effects of low frequency electromagnetic fields. Med War 1992; 8: 205-12.
Vincenzi F, Targa M, Corciulo C, et al. Pulsed electromagnetic fields increased the anti-inflammatory effect of A(2)A and A(3) adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PloS One 2013; 8: e65561.
Podda MV, Leone L, Barbati SA, et al. Extremely low-frequency electromagnetic fields enhance the survival of newborn neurons in the mouse hippocampus. Eur J Neurosci 2014; 39: 893-903.
Perez FP, Zhou X, Morisaki J, Jurivich D. Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response. Exp Gerontol 2008; 43: 307-16.
Baek S, Quan X, Kim S, Lengner C, Park JK, Kim J. Electromagnetic fields mediate efficient cell reprogramming into a Pluripotent State. ACS Nano 2014; 8: 10125-38.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe