Display options
Share it on

J Clin Med. 2019 Dec 24;9(1). doi: 10.3390/jcm9010050.

Application of Impedance-Based Techniques in Hepatology Research.

Journal of clinical medicine

Katie Morgan, Wesam Gamal, Kay Samuel, Steven D Morley, Peter C Hayes, Pierre Bagnaninchi, John N Plevris

Affiliations

  1. The University of Edinburgh Hepatology Laboratory, Division of Heath Sciences, University of Edinburgh Medical School, Chancellor's Building, Edinburgh BioQuarter, 49 Little France Crescent, EH16 4SB Edinburgh, UK.
  2. James Nasmyth Building, Institute of Mechanical, Process and Energy Engineering, Heriot-Watt University School of Engineering and Physical Sciences, EH14 4AS Edinburgh, UK.
  3. The Jack Copland Centre, Advanced Therapeutics, Scottish National Blood Transfusion Service, 52 Research Avenue North, EH14 4BE Edinburgh, UK.
  4. MRC Centre for Regenerative Medicine 5 Little France Drive, EH16 4UU Edinburgh, UK.

PMID: 31878354 PMCID: PMC7019217 DOI: 10.3390/jcm9010050

Abstract

There are a variety of end-point assays and techniques available to monitor hepatic cell cultures and study toxicity within in vitro models. These commonly focus on one aspect of cell metabolism and are often destructive to cells. Impedance-based cellular assays (IBCAs) assess biological functions of cell populations in real-time by measuring electrical impedance, which is the resistance to alternating current caused by the dielectric properties of proliferating of cells. While the uses of IBCA have been widely reported for a number of tissues, specific uses in the study of hepatic cell cultures have not been reported to date. IBCA monitors cellular behaviour throughout experimentation non-invasively without labelling or damage to cell cultures. The data extrapolated from IBCA can be correlated to biological events happening within the cell and therefore may inform drug toxicity studies or other applications within hepatic research. Because tight junctions comprise the blood/biliary barrier in hepatocytes, there are major consequences when these junctions are disrupted, as many pathologies centre around the bile canaliculi and flow of bile out of the liver. The application of IBCA in hepatology provides a unique opportunity to assess cellular polarity and patency of tight junctions, vital to maintaining normal hepatic function. Here, we describe how IBCAs have been applied to measuring the effect of viral infection, drug toxicity /IC50, cholangiopathies, cancer metastasis and monitoring of the gut-liver axis. We also highlight key areas of research where IBCAs could be used in future applications within the field of hepatology.

Keywords: ECIS; TEER; hepatology; impedance based cellular assay; liver; xCELLigence

Conflict of interest statement

The authors have no conflict of interest to declare with respect to this manuscript.

References

  1. Biosens Bioelectron. 2010 Jan 15;25(5):990-5 - PubMed
  2. Clin Chem. 2009 Apr;55(4):611-22 - PubMed
  3. PLoS One. 2009 Aug 10;4(8):e6561 - PubMed
  4. Sci Rep. 2017 Jan 30;7:37541 - PubMed
  5. Gastroenterology. 2015 Jan;148(1):30-6 - PubMed
  6. Gut. 2018 Oct 8;: - PubMed
  7. Fluids Barriers CNS. 2013 Jan 10;10(1):5 - PubMed
  8. PLoS One. 2013 Aug 16;8(8):e72708 - PubMed
  9. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 1;44:64-72 - PubMed
  10. J Lab Autom. 2015 Apr;20(2):107-26 - PubMed
  11. J Hepatol. 2013 Mar;58(3):625-9 - PubMed
  12. Jundishapur J Microbiol. 2015 May 31;8(5):e19279 - PubMed
  13. Biotechnol Bioeng. 2018 Nov;115(11):2817-2827 - PubMed
  14. J Cell Biol. 1973 Aug;58(2):390-400 - PubMed
  15. J Biomol Screen. 2011 Jul;16(6):575-87 - PubMed
  16. Anal Chem. 2018 Jan 2;90(1):912-919 - PubMed
  17. PLoS One. 2018 May 10;13(5):e0197101 - PubMed
  18. Hum Cell. 2018 Jul;31(3):261-267 - PubMed
  19. Annu Rev Physiol. 1998;60:121-42 - PubMed
  20. Materials (Basel). 2018 May 31;11(6): - PubMed
  21. J Virol. 2009 Aug;83(16):8012-20 - PubMed
  22. World J Gastroenterol. 2010 Jan 21;16(3):289-95 - PubMed
  23. Mod Pathol. 2006 Mar;19(3):460-9 - PubMed
  24. Gastroenterology. 1999 May;116(5):1176-83 - PubMed
  25. PLoS One. 2013;8(3):e59432 - PubMed
  26. Cell Biol Toxicol. 2012 Apr;28(2):69-87 - PubMed
  27. Hepatology. 1991 Feb;13(2):216-21 - PubMed
  28. Hepatology. 2011 Aug;54(2):406-17 - PubMed
  29. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15655-60 - PubMed
  30. J Neurosci Methods. 2011 Sep 15;200(2):173-80 - PubMed
  31. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6462-7 - PubMed
  32. Chem Biol. 2009 Jul 31;16(7):712-23 - PubMed
  33. Int J Biol Sci. 2010 Dec 14;6(7):796-805 - PubMed
  34. Cancer Res. 2007 Mar 15;67(6):2497-507 - PubMed
  35. Med Eng Phys. 2003 Mar;25(2):79-90 - PubMed
  36. Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9739-40 - PubMed
  37. Ann Occup Hyg. 2012 Jul;56(5):622-30 - PubMed
  38. J Cell Biol. 1973 Jun;57(3):815-36 - PubMed
  39. Hepatology. 2013 Apr;57(4):1518-29 - PubMed
  40. Hepatology. 2010 Jan;51(1):329-35 - PubMed
  41. Analyst. 2011 Jan 21;136(2):237-45 - PubMed
  42. Med Toxicol. 1987 Mar-Apr;2(2):112-60 - PubMed
  43. Biosens Bioelectron. 2018 Oct 15;117:207-216 - PubMed
  44. Toxicol In Vitro. 2015 Oct;29(7):1916-31 - PubMed
  45. mSphere. 2017 Apr 5;2(2): - PubMed
  46. Hepatology. 1994 Dec;20(6):1437-41 - PubMed
  47. Biosensors (Basel). 2013 Mar 15;3(1):132-56 - PubMed
  48. Cancer Res. 1982 Sep;42(9):3858-63 - PubMed
  49. Biosens Bioelectron. 2013 Nov 15;49:63-70 - PubMed
  50. Biomed Pharmacother. 2019 Mar;111:1408-1416 - PubMed
  51. J Hepatol. 2017 Nov;67(5):1084-1103 - PubMed
  52. Med Electron Microsc. 2003 Sep;36(3):157-64 - PubMed
  53. Cytotechnology. 2015 Mar;67(2):379-86 - PubMed
  54. J Neurosci Methods. 2012 May 30;207(1):91-6 - PubMed
  55. Toxicol Lett. 2012 Jun 20;211(3):220-31 - PubMed
  56. Analyst. 2018 Aug 20;143(17):4189-4198 - PubMed
  57. J Virol. 2016 Jul 27;90(16):7159-70 - PubMed
  58. Eur J Pharm Sci. 2013 Mar 12;48(4-5):767-74 - PubMed
  59. J Neurosci Methods. 2012 Jan 15;203(1):69-77 - PubMed
  60. Food Chem Toxicol. 2017 Dec;110:1-12 - PubMed
  61. J Gen Virol. 2017 Mar;98(3):405-412 - PubMed
  62. J Immunol. 2016 Jul 15;197(2):630-43 - PubMed
  63. Toxicol In Vitro. 2012 Dec;26(8):1278-85 - PubMed
  64. Biosens Bioelectron. 2013 Dec 15;50:453-9 - PubMed
  65. Toxicol In Vitro. 2013 Aug;27(5):1589-95 - PubMed
  66. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3761-4 - PubMed
  67. Lab Invest. 2014 Oct;94(10):1126-33 - PubMed

Publication Types