Ex Vivo Studies

  • Amandeep KaurEmail author
Part of the Springer Theses book series (Springer Theses)


As outlined in Chap.  6, cultured cells have become an indispensable technology in various branches of life sciences. However, there are some concerns associated with the study of cultured cells.


  1. 1.
    G. Kaur, J.M. Dufour, Cell lines. Spermatogenesis 2, 1–5 (2012)Google Scholar
  2. 2.
    J.R. Masters, G.N. Stacey, Changing medium and passaging cell lines. Nat. Protocols 2, 2276–2284 (2007)CrossRefGoogle Scholar
  3. 3.
    M. Lacroix, Persistent use of false cell lines. Int. J. Cancer 122, 1–4 (2008)CrossRefGoogle Scholar
  4. 4.
    J.-P. Gillet, S. Varma, M.M. Gottesman, The clinical relevance of cancer cell lines. J. Natl. Cancer Inst. 105, 452–458 (2013)CrossRefGoogle Scholar
  5. 5.
    I. Garitaonandia, H. Amir, F.S. Boscolo, G.K. Wambua, H.L. Schultheisz, K. Sabatini, R. Morey, S. Waltz, Y.-C. Wang, H. Tran, T.R. Leonardo, K. Nazor, I. Slavin, C. Lynch, Y. Li, R. Coleman, I. Gallego Romero, G. Altun, D. Reynolds, S. Dalton, M. Parast, J.F. Loring, L.C. Laurent, Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions. PLoS ONE 10, e0118307 (2015)CrossRefGoogle Scholar
  6. 6.
    C. Pan, C. Kumar, S. Bohl, U. Klingmueller, M. Mann, Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions. Mol. Cellular Proteomics 8, 443–450 (2009)CrossRefGoogle Scholar
  7. 7.
    S. Wilkening, F. Stahl, A. Bader, comparison of primary human hepatocytes and hepatoma cell line HEPG2 with regard to their biotransformation properties. Drug Metab. Dispos. 31, 1035–1042 (2003)CrossRefGoogle Scholar
  8. 8.
    V. Sanchez-Valle, N.C. Chavez-Tapia, M. Uribe, N. Mendez-Sanchez, Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr. Med. Chem. 19, 4850–4860 (2012)CrossRefGoogle Scholar
  9. 9.
    C. Guguen-Guillouzo, A. Guillouzo, General review on in vitro hepatocyte models and their applications, in Methods in Molecular Biology, ed. by N.J. Clifton, vol. 640 (2010), pp. 1–40Google Scholar
  10. 10.
    C. Garcia-Ruiz, J.C. Fernandez-Checa, Redox regulation of hepatocyte apoptosis. J. Gastroenterol. Hepatol. 22(Suppl 1), S38–42 (2007)CrossRefGoogle Scholar
  11. 11.
    R. Singh, M.J. Czaja, Regulation of hepatocyte apoptosis by oxidative stress. J. Gastroenterol. Hepatol. 22(Suppl 1), S45–8 (2007)CrossRefGoogle Scholar
  12. 12.
    I. Kurose, H. Higuchi, S. Miura, H. Saito, N. Watanabe, R. Hokari, M. Hirokawa, M. Takaishi, S. Zeki, T. Nakamura, H. Ebinuma, S. Kato, H. Ishii, Oxidative stress-mediated apoptosis of hepatocytes exposed to acute ethanol intoxication. Hepatology 25, 368–378 (1997)CrossRefGoogle Scholar
  13. 13.
    Y. Sumida, E. Niki, Y. Naito, T. Yoshikawa, Involvement of free radicals and oxidative stress in NAFLD/NASH. Free Radic. Res. 47, 869–880 (2013)CrossRefGoogle Scholar
  14. 14.
    M.D. Norenberg, A.R. Jayakumar, K.V. Rama, Rao, oxidative stress in the pathogenesis of hepatic encephalopathy. Metab. Brain Dis. 19, 313–329 (2004)CrossRefGoogle Scholar
  15. 15.
    H. Tsukamoto, Oxidative stress, antioxidants, and alcoholic liver fibrogenesis, in Alcohol (Fayetteville, N.Y.), vol. 10 (1993), pp. 465–467Google Scholar
  16. 16.
    S. Pal, S.J. Polyak, N. Bano, W.C. Qiu, R.L. Carithers, M. Shuhart, D.R. Gretch, A. Das, Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1. J. Gastroenterol. Hepatol. 25, 627–634 (2010)CrossRefGoogle Scholar
  17. 17.
    H. Cichoż-Lach, A. Michalak, Oxidative stress as a crucial factor in liver diseases. World J. Gastroenterol. WJG 20, 8082–8091 (2014)Google Scholar
  18. 18.
    B. Saberi, M. Shinohara, M.D. Ybanez, N. Hanawa, W.A. Gaarde, N. Kaplowitz, D. Han, Regulation of H(2)O(2)-induced necrosis by PKC and AMP-activated kinase signaling in primary cultured hepatocytes. Am. J. Physiol. Cell Physiol. 295, C50–63 (2008)CrossRefGoogle Scholar
  19. 19.
    M.G. Cotticelli, A.M. Crabbe, R.B. Wilson, M.S. Shchepinov, Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids. Redox Biol. 1, 398–404 (2013)CrossRefGoogle Scholar
  20. 20.
    S. Hill, C.R. Lamberson, L. Xu, R. To, H.S. Tsui, V.V. Shmanai, A.V. Bekish, A.M. Awad, B.N. Marbois, C.R. Cantor, N.A. Porter, C.F. Clarke, M.S. Shchepinov, Small amounts of isotope-reinforced polyunsaturated fatty acids suppress lipid autoxidation. Free Radic. Biol. Med. 53, 893–906 (2012)CrossRefGoogle Scholar
  21. 21.
    L.A. Herzenberg, D. Parks, B. Sahaf, O. Perez, M. Roederer, L.A. Herzenberg, The history and future of the fluorescence activated cell sorter and flow cytometry: a view from stanford. Clin. Chem. 48, 1819–1827 (2002)Google Scholar
  22. 22.
    Regenerative Medicine, Technical report, Department of Health and Human ServicesGoogle Scholar
  23. 23.
    D. Levitt, R. Mertelsmann, Hematopoietic Stem Cells: Biology and Therapeutic Applications (Taylor & Francis, 1995)Google Scholar
  24. 24.
    C.J. Eaves, Hematopoietic stem cells: concepts, definitions, and the new reality. Blood 125, 2605–2613 (2015)CrossRefGoogle Scholar
  25. 25.
    I. Godin, A. Cumano, Hematopoietic Stem Cell Development (Medical Intelligence Unit, Springer, US, 2010)Google Scholar
  26. 26.
    M. Kondo, Hematopoietic Stem Cell Biology. Stem Cell Biology and Regenerative Medicine (Humana Press, 2009)Google Scholar
  27. 27.
    D. Hernandez-Garcia, C.D. Wood, S. Castro-Obregon, L. Covarrubias, Reactive oxygen species: a radical role in development? Free Radic. Biol. Med. 49, 130–143 (2010)CrossRefGoogle Scholar
  28. 28.
    H. Sandoval, P. Thiagarajan, S.K. Dasgupta, A. Schumacher, J.T. Prchal, M. Chen, J. Wang, Essential role for Nix in autophagic maturation of erythroid cells. Nature 454, 232–235 (2008)CrossRefGoogle Scholar
  29. 29.
    N.A. Maianski, J. Geissler, S.M. Srinivasula, E.S. Alnemri, D. Roos, T.W. Kuijpers, Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis. Cell Death Differ. 11, 143–153 (2004)CrossRefGoogle Scholar
  30. 30.
    C. Nombela-Arrieta, G. Pivarnik, B. Winkel, K.J. Canty, B. Harley, J.E. Mahoney, S.-Y. Park, J. Lu, A. Protopopov, L.E. Silberstein, Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat. Cell Biol. 15, 533–543 (2013)CrossRefGoogle Scholar
  31. 31.
    H.M. Shapiro, Practical Flow Cytometry (Wiley, 2005)Google Scholar
  32. 32.
    S.T. Fraser, R.G. Midwinter, B.S. Berger, R. Stocker, Heme oxygenase-1: a critical link between iron metabolism, erythropoiesis, and development. Adv. Hematol. 2011, 473709 (2011)CrossRefGoogle Scholar
  33. 33.
    J. Isern, S.T. Fraser, Z. He, M.H. Baron, Developmental niches for embryonic erythroid cells. Blood Cells Molecules Dis. 44, 207–208 (2010)CrossRefGoogle Scholar
  34. 34.
    K. McGrath, J. Palis, Ontogeny of erythropoiesis in the mammalian embryo. Curr. Top. Dev. Biol. 82, 1–22 (2008)CrossRefGoogle Scholar
  35. 35.
    P.D. Kingsley, J. Malik, K.A. Fantauzzo, J. Palis, Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis. Blood 104, 19–25 (2004)CrossRefGoogle Scholar
  36. 36.
    S.T. Fraser, J. Isern, M.H. Baron, Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression. Blood 109, 343–352 (2006)CrossRefGoogle Scholar
  37. 37.
    M. Socolovsky, Molecular insights into stress erythropoiesis. Curr. Opin. Hematol. 14, 215–224 (2007)CrossRefGoogle Scholar
  38. 38.
    M.H. Baron, Embryonic origins of mammalian hematopoiesis. Exp. Hematol. 31, 1160–1169 (2003)CrossRefGoogle Scholar
  39. 39.
    K. Ito, A. Hirao, F. Arai, S. Matsuoka, K. Takubo, I. Hamaguchi, K. Nomiyama, K. Hosokawa, K. Sakurada, N. Nakagata, Y. Ikeda, T.W. Mak, T. Suda, Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431, 997–1002 (2004)CrossRefGoogle Scholar
  40. 40.
    Y.-Y. Jang, S.J. Sharkis, A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110, 3056–3063 (2007)CrossRefGoogle Scholar
  41. 41.
    P. Rimmelé, C. Bigarella, R. Liang, B. Izac, R. Dieguez-Gonzalez, G. Barbet, M. Donovan, C. Brugnara, J. Blander, D. Sinclair, S. Ghaffari, Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells. Stem Cell Rep. 3, 44–59 (2016)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.School of ChemistryUniversity of SydneySydneyAustralia

Personalised recommendations