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A Novel Approach for In Vitro Studies Applying Electrical Fields to Cell Cultures by Transformer-Like Coupling

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Abstract

The purpose of this study was to develop a new apparatus for in vitro studies applying low frequency electrical fields to cells without interfering side effects like biochemical reactions or magnetic fields which occur in currently available systems. We developed a non-invasive method by means of the principle of transformer-like coupling where the magnetic field is concentrated in a toroid and, therefore, does not affect the cell culture. Next to an extensive characterization of the electrical field parameters, initial cell culture studies have focused on examining the response of bone marrow-derived human mesenchymal stem cells (MSCs) to pulsed electrical fields. While no significant differences in the proliferation of human MSCs could be detected, significant increases in ALP activity as well as in gene expression of other osteogenic markers were observed. The results indicate that transformer-like coupled electrical fields can be used to influence osteogenic differentiation of human MSCs in vitro and can pose a useful tool in understanding the influence of electrical fields on the cellular and molecular level.

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References

  1. Roux, W. (1885). Beitrag zur Morphologie der funktionellen Anpassung. Archives d’Anatomie et de Cytologie Pathologiques, 9, 120–158.

    Google Scholar 

  2. Wolff, J. (1892). Das Gesetz der Transformation von Knochen. Berlin: Verlag von August Hirschwald.

    Google Scholar 

  3. Prince, R. L., Smith, M., Dick, I. M., Price, R. I., Webb, P. G., Henderson, N. K., et al. (1991). Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy. New England Journal of Medicine, 325, 1189–1195.

    Article  PubMed  CAS  Google Scholar 

  4. Bassey, E. J., & Ramsdale, S. J. (1994). Increase in femoral bone density in young women following high-impact exercise. Osteoporosis International, 4, 72–75.

    Article  PubMed  CAS  Google Scholar 

  5. Morey, E. R., & Baylink, D. J. (1978). Inhibition of bone formation during space flight. Science, 201, 1138–1141.

    Article  PubMed  CAS  Google Scholar 

  6. Rambaut, P. C., & Goode, A. W. (1985). Skeletal changes during space flight. Lancet, 2, 1050–1052.

    Article  PubMed  CAS  Google Scholar 

  7. Fukada, E., & Yasuda, I. (1957). On the piezoelectric effect of bone. Journal of the Physical Society of Japan, 12, 121–128.

    Article  Google Scholar 

  8. Bassett, C. A. (1968). Biologic significance of piezoelectricity. Calcified Tissue Research, 1, 252–272.

    Article  PubMed  CAS  Google Scholar 

  9. Friedenberg, Z. B., & Brighton, C. T. (1966). Bioelectric potentials in bone. Journal of Bone and Joint Surgery. American Volume, 48, 915–923.

    CAS  Google Scholar 

  10. Brighton, C. T., Black, J., Friedenberg, Z. B., Esterhai, J. L., Day, L. J., & Connolly, J. F. (1981). A multicenter study of the treatment of non-union with constant direct current. Journal of Bone and Joint Surgery. American Volume, 63, 2–13.

    CAS  Google Scholar 

  11. Paterson, D. (1984). Treatment of nonunion with a constant direct current: A totally implantable system. Orthopedic Clinics of North America, 15, 47–59.

    PubMed  CAS  Google Scholar 

  12. Brighton, C., & Pollack, S. (1985). Treatment of recalcitrant non-union with a capacitively coupled electrical field. A preliminary report. Journal of Bone and Joint Surgery. American Volume, 67, 577–585.

    CAS  Google Scholar 

  13. Goodwin, C. B., Brighton, C. T., Guyer, R. D., Johnson, J. R., Light, K. I., & Yuan, H. A. (1999). A double-blind study of capacitively coupled electrical stimulation as an adjunct to lumbar spinal fusions. Spine (Phila Pa 1976), 24, 1349–1356; discussion 1357.

  14. Bassett, C. A., Mitchell, S. N., & Gaston, S. R. (1981). Treatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fields. Journal of Bone and Joint Surgery. American Volume, 63, 511–523.

    CAS  Google Scholar 

  15. Chang, W. H., Hwang, I. M., & Liu, H. C. (1991). Enhancement of fracture healing by specific pulsed capacitively-coupled electric field stimulation. Frontiers of Medical and Biological Engineering, 3, 57–64.

    PubMed  CAS  Google Scholar 

  16. Ciombor, D. M., & Aaron, R. K. (1993). Influence of electromagnetic fields on endochondral bone formation. Journal of Cellular Biochemistry, 52, 37–41.

    Article  PubMed  CAS  Google Scholar 

  17. Black, J. (1987). Electrical stimulation—its role in growth, repair, and remodeling of the musculoskeletal system. New York: Praeger.

    Google Scholar 

  18. Supronowicz, P. R., Ajayan, P. M., Ullmann, K. R., Arulanandam, B. P., Metzger, D. W., & Bizios, R. (2002). Novel current-conducting composite substrates for exposing osteoblasts to alternating current stimulation. Journal of Biomedical Materials Research, 59, 499–506.

    Article  PubMed  CAS  Google Scholar 

  19. Midura, R. J., Ibiwoye, M. O., Powell, K. A., Sakai, Y., Doehring, T., Grabiner, M. D., et al. (2005). Pulsed electromagnetic field treatments enhance the healing of fibular osteotomies. The Journal of Orthopaedic Research, 23, 1035–1046.

    Article  Google Scholar 

  20. Fini, M., Cadossi, R., Canè, V., Cavani, F., Giavaresi, G., Krajewski, A., et al. (2002). The effect of pulsed electromagnetic fields on the osteointegration of hydroxyapatite implants in cancellous bone: A morphologic and microstructural in vivo study. The Journal of Orthopaedic Research, 20, 756–763.

    Article  CAS  Google Scholar 

  21. Jansen, J. H. W., van der Jagt, O. P., Punt, B. J., Verhaar, J. A. N., van Leeuwen, J. P. T. M., Weinans, H., et al. (2010). Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: An in vitro study. BMC Musculoskeletal Disorders, 11, 188.

    Article  PubMed  Google Scholar 

  22. Sun, L.-Y., Hsieh, D.-K., Lin, P.-C., Chiu, H.-T., & Chiou, T.-W. (2010). Pulsed electromagnetic fields accelerate proliferation and osteogenic gene expression in human bone marrow mesenchymal stem cells during osteogenic differentiation. Bioelectromagnetics, 31, 209–219.

    Article  PubMed  CAS  Google Scholar 

  23. Tsai, M.-T., Li, W.-J., Tuan, R. S., & Chang, W. H. (2009). Modulation of osteogenesis in human mesenchymal stem cells by specific pulsed electromagnetic field stimulation. The Journal of Orthopaedic Research, 27, 1169–1174.

    Article  Google Scholar 

  24. Sollazzo, V., Palmieri, A., Pezzetti, F., Massari, L., & Carinci, F. (2010). Effects of pulsed electromagnetic fields on human osteoblastlike cells (mg-63): A pilot study. Clinical Orthopaedics and Related Research, 468, 2260–2277.

    Article  PubMed  Google Scholar 

  25. Aaron, R. K., Ciombor, D. M., & Simon, B. J. (2004). Treatment of nonunions with electric and electromagnetic fields. Clinical Orthopaedics and Related Research, 419, 21–29.

    Google Scholar 

  26. Chang, K., Chang, W. H.-S., Wu, M.-L., & Shih, C. (2003). Effects of different intensities of extremely low frequency pulsed electromagnetic fields on formation of osteoclast-like cells. Bioelectromagnetics, 24, 431–439.

    Article  PubMed  Google Scholar 

  27. Heermeier, K., Spanner, M., Träger, J., Gradinger, R., Strauss, P. G., Kraus, W., et al. (1998). Effects of extremely low frequency electromagnetic field (EMF) on collagen type I mRNA expression and extracellular matrix synthesis of human osteoblastic cells. Bioelectromagnetics, 19, 222–231.

    Article  PubMed  CAS  Google Scholar 

  28. Haddad, J. B., Obolensky, A. G., & Shinnick, P. (2007). The biologic effects and the therapeutic mechanism of action of electric and electromagnetic field stimulation on bone and cartilage: New findings and a review of earlier work. The Journal of Alternative and Complementary Medicine, 13, 485–490.

    Article  PubMed  Google Scholar 

  29. Verfahren und Vorrichtung zur Einkopplung eines elektrischen Feldes in ein physiologisches und elektrisch leitfähiges Medium. DE Patent 102006015550 B4, 2006.

  30. Rentsch, B., Hofmann, A., Breier, A., Rentsch, C., & Scharnweber, D. (2009). Embroidered and surface modified polycaprolactone-co-lactide scaffolds as bone substitute: In vitro characterization. Annals of Biomedical Engineering, 37, 2118–2128.

    Article  PubMed  Google Scholar 

  31. Oswald, J., Boxberger, S., Jørgensen, B., Feldmann, S., Ehninger, G., Bornhäuser, M., et al. (2004). Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells, 22, 377–384.

    Article  PubMed  Google Scholar 

  32. Wollenweber, M., Domaschke, H., Hanke, T., Boxberger, S., Schmack, G., Gliesche, K., et al. (2006). Mimicked bioartificial matrix containing chondroitin sulphate on a textile scaffold of poly(3-hydroxybutyrate) alters the differentiation of adult human mesenchymal stem cells. Tissue Engineering, 12, 345–359.

    Article  PubMed  CAS  Google Scholar 

  33. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative pcr and the 2(−delta delta c(t)) method. Methods, 25, 402–408.

    Article  PubMed  CAS  Google Scholar 

  34. Lunze, K. (1991). Einführung in die Elektrotechnik (13th ed.). Berlin: Verlag Technik.

    Google Scholar 

  35. Aaron, R. K., & Ciombor, D. M. (1996). Acceleration of experimental endochondral ossification by biophysical stimulation of the progenitor cell pool. The Journal of Orthopaedic Research, 14, 582–589.

    Article  CAS  Google Scholar 

  36. Schwartz, Z., Simon, B. J., Duran, M. A., Barabino, G., Chaudhri, R., & Boyan, B. D. (2008). Pulsed electromagnetic fields enhance BMP-2 dependent osteoblastic differentiation of human mesenchymal stem cells. The Journal of Orthopaedic Research, 26, 1250–1255.

    Article  CAS  Google Scholar 

  37. Esposito, M., Lucariello, A., Riccio, I., Riccio, V., Esposito, V., & Riccardi, G. (2012). Differentiation of human osteoprogenitor cells increases after treatment with pulsed electromagnetic fields. In vivo, 26, 299–304.

    PubMed  Google Scholar 

  38. Hammerick, K. E., James, A. W., Huang, Z., Prinz, F. B., & Longaker, M. T. (2010). Pulsed direct current electric fields enhance osteogenesis in adipose-derived stromal cells. Tissue Engineering Part A, 16, 917–931.

    Article  PubMed  CAS  Google Scholar 

  39. Hronik-Tupaj, M., Rice, W. L., Cronin-Golomb, M., Kaplan, D. L., & Georgakoudi, I. (2011). Osteoblastic differentiation and stress response of human mesenchymal stem cells exposed to alternating current electric fields. Biomedical Engineering Online, 10, 9.

    Article  PubMed  Google Scholar 

  40. Kim, I. S., Song, J. K., Song, Y. M., Cho, T. H., Lee, T. H., Lim, S. S., et al. (2009). Novel effect of biphasic electric current on in vitro osteogenesis and cytokine production in human mesenchymal stromal cells. Tissue Engineering Part A, 15, 2411–2422.

    Article  PubMed  CAS  Google Scholar 

  41. Sun, S., Liu, Y., Lipsky, S., & Cho, M. (2007). Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells. FASEB Journal, 21, 1472–1480.

    Article  PubMed  CAS  Google Scholar 

  42. Marom, R., Shur, I., Solomon, R., & Benayahu, D. (2005). Characterization of adhesion and differentiation markers of osteogenic marrow stromal cells. Journal of Cellular Physiology, 202, 41–48.

    Article  PubMed  CAS  Google Scholar 

  43. Luo, F., Hou, T., Zhang, Z., Xie, Z., Wu, X., & Xu, J. (2012). Effects of pulsed electromagnetic field frequencies on the osteogenic differentiation of human mesenchymal stem cells. Orthopedics, 35, e526–e531.

    Article  PubMed  Google Scholar 

  44. Sul, A. R., Park, S.-N., & Suh, H. (2006). Effects of sinusoidal electromagnetic field on structure and function of different kinds of cell lines. Yonsei Medical Journal, 47, 852–861.

    Article  PubMed  Google Scholar 

  45. Bisceglia, B., Zirpoli, H., Caputo, M., Chiadini, F., Scaglione, A., & Tecce, M. F. (2011). Induction of alkaline phosphatase activity by exposure of human cell lines to a low-frequency electric field from apparatuses used in clinical therapies. Bioelectromagnetics, 32, 113–119.

    Article  PubMed  Google Scholar 

  46. Diniz, P., Shomura, K., Soejima, K., & Ito, G. (2002). Effects of pulsed electromagnetic field (PEMF) stimulation on bone tissue like formation are dependent on the maturation stages of the osteoblasts. Bioelectromagnetics, 23, 398–405.

    Article  PubMed  Google Scholar 

  47. Tsai, M.-T., Chang, W. H.-S., Chang, K., Hou, R.-J., & Wu, T.-W. (2007). Pulsed electromagnetic fields affect osteoblast proliferation and differentiation in bone tissue engineering. Bioelectromagnetics, 28, 519–528.

    Article  PubMed  CAS  Google Scholar 

  48. Matsunaga, S., Sakou, T., & Ijiri, K. (1996). Osteogenesis by pulsing electromagnetic fields (PEMFs): Optimum stimulation setting. In vivo, 10, 351–356.

    PubMed  CAS  Google Scholar 

  49. Dubey, A. K., Gupta, S. D., & Basu, B. (2011). Optimization of electrical stimulation parameters for enhanced cell proliferation on biomaterial surfaces. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 98, 18–29.

    Article  Google Scholar 

  50. Brighton, C. T., Wang, W., Seldes, R., Zhang, G., & Pollack, S. R. (2001). Signal transduction in electrically stimulated bone cells. Journal of Bone and Joint Surgery. American Volume, 83-A, 1514–1523.

    CAS  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the DFG TRR 67 for financial support and the Catgut GmbH (Markneukirchen, Germany) for providing PCL scaffolds. Furthermore, the authors thank Katrin Müller, group Professor M. Bornhäuser, Medical Clinic I, Dresden University Hospital Carl Gustav Carus for providing human MSCs. DAH was supported by the Alberta Innovates Health Solutions/Alberta Heritage Foundation for Medical Research Team Grant in Osteoarthritis.

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Authors and Affiliations

  1. Max Bergmann Center of Biomaterials, TU Dresden, Budapester Str. 27, 01069, Dresden, Germany

    R. Hess, A. Seifert, S. Bierbaum & D. Scharnweber

  2. Institute of Electromechanical and Electronic Design, TU Dresden, Helmholtzstr. 10, 01069, Dresden, Germany

    H. Neubert

  3. McCaig Institute of Bone and Joint Health, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 1N4, Canada

    D. A. Hart

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  1. R. Hess
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  2. H. Neubert
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  6. D. Scharnweber
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Correspondence to D. Scharnweber.

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Hess, R., Neubert, H., Seifert, A. et al. A Novel Approach for In Vitro Studies Applying Electrical Fields to Cell Cultures by Transformer-Like Coupling. Cell Biochem Biophys 64, 223–232 (2012). https://doi.org/10.1007/s12013-012-9388-4

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