Advertisement

Isolation and Characterization of Stem Cells from Human Central Nervous System Malignancies

  • Imad Saeed Khan
  • Moneeb EhteshamEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 853)

Abstract

Central Nervous System (CNS) tumors include some of the most invasive and lethal tumors in humans. The poor prognosis in patients with CNS tumors is ascribed to their invasive nature. After the description of a stem cell-like cohort in hematopoietic cancers, tumor stem cells (TSCs) have been isolated from a variety of solid tumors, including brain tumors. Further research has uncovered the crucial role these cells play in the initiation and propagation of brain tumors. More importantly, TSCs have also been shown to be relatively resistant to conventional cytotoxic therapeutics, which may also account for the alarmingly high rate of CNS tumor recurrence. In order to elucidate prospective therapeutic targets it is imperative to study these cells in detail and to accomplish this, we need to be able to reliably isolate and characterize these cells. This chapter will therefore, provide an overview of the methods used to isolate and characterize stem cells from human CNS malignancies.

Keywords

Glioma stem cells Tumor stem cells Cancer stem cells Stem cell sorting Hoechst dye exclusion ALDH1 assay Neurosphere culture 

References

  1. 1.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMedGoogle Scholar
  2. 2.
    Rich JN, Eyler CE. Cancer stem cells in brain tumor biology. Cold Spring Harb Symp Quant Biol. 2008;73:411–20.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CHM, Jones DL, et al. Cancer stem cells: perspectives on current status and future directions—AACR Workshop on cancer stem cells. Cancer Res. 2006;66(19):9339–44.CrossRefPubMedGoogle Scholar
  4. 4.
    Ehtesham M, Mapara KY, Stevenson CB, Thompson RC. CXCR4 mediates the proliferation of glioblastoma progenitor cells. Cancer Lett. 2009;274(2):305–12.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol. 2008;26(17):2839–45.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, et al. Stem cell–like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006;66(16):7843–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Rycaj K, Tang DG. Cancer stem cells and radioresistance. Int J Radiat Biol. 2014;90:615–21.CrossRefPubMedGoogle Scholar
  8. 8.
    Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine. 2012;7(4):597–615.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Grimes C, Margolin DA, Li L. Are cancer stem cells responsible for cancer recurrence? Cell Biol Res Ther [Internet]. 2012 [cited 2014 Jun 10];01(01). Available from: http://www.scitechnol.com/cancer-stem-cells-responsible-for-cancer-recurrence-C6I7.php?article_id=63.
  10. 10.
    Yu Y, Ramena G, Elble RC. The role of cancer stem cells in relapse of solid tumors. Front Biosci (Elite Ed). 2012;4:1528–41.CrossRefGoogle Scholar
  11. 11.
    Dobbin ZC, Landen CN. Isolation and characterization of potential cancer stem cells from solid human tumors: potential applications. Curr Protoc Pharmacol. 2013;63:Unit 14.28.Google Scholar
  12. 12.
    Guerrero-Cázares H, Chaichana KL, Quiñones-Hinojosa A. Neurosphere culture and human organotypic model to evaluate brain tumor stem cells. Methods Mol Biol. 2009;568:73–83.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Mizrak D, Brittan M, Alison MR. CD133: molecule of the moment. J Pathol. 2008;214(1):3–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Corbeil D, Fargeas CA, Huttner WB. Rat prominin, like its mouse and human orthologues, is a pentaspan membrane glycoprotein. Biochem Biophys Res Commun. 2001;285(4):939–44.CrossRefPubMedGoogle Scholar
  15. 15.
    Weigmann A, Corbeil D, Hellwig A, Huttner WB. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci U S A. 1997;94(23):12425–30.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90(12): 5002–12.PubMedGoogle Scholar
  17. 17.
    Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997;90(12):5013–21.PubMedGoogle Scholar
  18. 18.
    Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D. Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells. Blood. 1999;93(4):1435–7.PubMedGoogle Scholar
  19. 19.
    Bühring HJ, Seiffert M, Marxer A, Weiss B, Faul C, Kanz L, et al. AC133 antigen expression is not restricted to acute myeloid leukemia blasts but is also found on acute lymphoid leukemia blasts and on a subset of CD34+ B-cell precursors. Blood. 1999;94(2):832–3.PubMedGoogle Scholar
  20. 20.
    Neuzil J, Stantic M, Zobalova R, Chladova J, Wang X, Prochazka L, et al. Tumour-initiating cells vs. cancer “stem” cells and CD133: what’s in the name? Biochem Biophys Res Commun. 2007;355(4):855–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63(18):5821–8.PubMedGoogle Scholar
  22. 22.
    Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401.CrossRefPubMedGoogle Scholar
  23. 23.
    Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003;100(25):15178–83.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Dell’Albani P. Stem cell markers in gliomas. Neurochem Res. 2008;33(12):2407–15.CrossRefPubMedGoogle Scholar
  25. 25.
    Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990;60(4):585–95.CrossRefPubMedGoogle Scholar
  26. 26.
    Hockfield S, McKay RD. Identification of major cell classes in the developing mammalian nervous system. J Neurosci. 1985;5(12):3310–28.PubMedGoogle Scholar
  27. 27.
    Strojnik T, Røsland GV, Sakariassen PO, Kavalar R, Lah T. Neural stem cell markers, nestin and musashi proteins, in the progression of human glioma: correlation of nestin with prognosis of patient survival. Surg Neurol. 2007;68(2):133–43. discussion 143–144.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhang M, Song T, Yang L, Chen R, Wu L, Yang Z, et al. Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res. 2008;27:85.CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Emmenegger BA, Wechsler-Reya RJ. Stem cells and the origin and propagation of brain tumors. J Child Neurol. 2008;23(10):1172–8.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Sotelo C, Alvarado-Mallart RM, Frain M, Vernet M. Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells. J Neurosci. 1994;14(1):124–33.PubMedGoogle Scholar
  31. 31.
    Alder J, Cho NK, Hatten ME. Embryonic precursor cells from the rhombic lip are specified to a cerebellar granule neuron identity. Neuron. 1996;17(3):389–99.CrossRefPubMedGoogle Scholar
  32. 32.
    Lee A, Kessler JD, Read T-A, Kaiser C, Corbeil D, Huttner WB, et al. Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci. 2005;8(6):723–9.CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Pfenninger CV, Roschupkina T, Hertwig F, Kottwitz D, Englund E, Bengzon J, et al. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells. Cancer Res. 2007;67(12):5727–36.CrossRefPubMedGoogle Scholar
  34. 34.
    Eyler CE, Foo W-C, LaFiura KM, McLendon RE, Hjelmeland AB, Rich JN. Brain cancer stem cells display preferential sensitivity to Akt inhibition. Stem Cells. 2008;26(12):3027–36.CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Pavon LF, Marti LC, Sibov TT, Miyaki LAM, Malheiros SMF, Mamani JB, et al. Isolation, cultivation and characterization of CD133+ stem cells from human glioblastoma. Einstein São Paulo Braz. 2012;10(2):197–202.CrossRefGoogle Scholar
  36. 36.
    Shin DH, Xuan S, Kim W-Y, Bae G-U, Kim J-S. CD133 antibody-conjugated immunoliposomes encapsulating gemcitabine for targeting glioblastoma stem cells. J Mater Chem B. 2014;2(24):3771–81.CrossRefGoogle Scholar
  37. 37.
    Latt SA, Stetten G, Juergens LA, Willard HF, Scher CD. Recent developments in the detection of deoxyribonucleic acid synthesis by 33258 Hoechst fluorescence. J Histochem Cytochem. 1975;23(7):493–505.CrossRefPubMedGoogle Scholar
  38. 38.
    Latt SA, Stetten G. Spectral studies on 33258 Hoechst and related bisbenzimidazole dyes useful for fluorescent detection of deoxyribonucleic acid synthesis. J Histochem Cytochem. 1976;24(1):24–33.CrossRefPubMedGoogle Scholar
  39. 39.
    Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183(4):1797–806.CrossRefPubMedGoogle Scholar
  40. 40.
    Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G, et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med. 1997;3(12):1337–45.CrossRefPubMedGoogle Scholar
  41. 41.
    Srivastava VK, Nalbantoglu J. Flow cytometric characterization of the DAOY medulloblastoma cell line for the cancer stem-like phenotype. Cytometry A. 2008;73(10):940–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Shen G, Shen F, Shi Z, Liu W, Hu W, Zheng X, et al. Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. In Vitro Cell Dev Biol Anim. 2008;44(7):280–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Feuring-Buske M, Hogge DE. Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34(+)CD38(−) progenitor cells from patients with acute myeloid leukemia. Blood. 2001;97(12):3882–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Kai K, D’Costa S, Yoon B-I, Brody AR, Sills RC, Kim Y. Characterization of side population cells in human malignant mesothelioma cell lines. Lung Cancer Amst Neth. 2010;70(2):146–51.CrossRefGoogle Scholar
  45. 45.
    Holyoake T, Jiang X, Eaves C, Eaves A. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood. 1999;94(6):2056–64.PubMedGoogle Scholar
  46. 46.
    She J-J, Zhang P-G, Che X-M, Wang X, Wang Z-M. Side population cells from HXO-Rb44 retinoblastoma cell line have cancer-initiating property. Int J Ophthalmol. 2011;4(5):461–5.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Qi W, Zhao C, Zhao L, Liu N, Li X, Yu W, et al. Sorting and identification of side population cells in the human cervical cancer cell line HeLa. Cancer Cell Int. 2014;14(1):3.CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Xu Y, Xie Y, Wang X, Chen X, Liu Q, Ying M, et al. Identification of cancer stem cells from hepatocellular carcinoma cell lines and their related microRNAs. Oncol Rep. 2013;30(5):2056–62.PubMedGoogle Scholar
  49. 49.
    Smith PJ, Furon E, Wiltshire M, Campbell L, Feeney GP, Snyder RD, et al. ABCG2-associated resistance to Hoechst 33342 and topotecan in a murine cell model with constitutive expression of side population characteristics. Cytometry A. 2009;75(11):924–33.CrossRefPubMedGoogle Scholar
  50. 50.
    Zheng X, Shen G, Yang X, Liu W. Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res. 2007;67(8):3691–7.CrossRefPubMedGoogle Scholar
  51. 51.
    Broadley KWR, Hunn MK, Farrand KJ, Price KM, Grasso C, Miller RJ, et al. Side population is not necessary or sufficient for a cancer stem cell phenotype in glioblastoma multiforme. Stem Cells. 2011;29(3):452–61.CrossRefPubMedGoogle Scholar
  52. 52.
    Marchitti SA, Brocker C, Stagos D, Vasiliou V. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol. 2008;4(6):697–720.CrossRefPubMedCentralPubMedGoogle Scholar
  53. 53.
    Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 2011;7(2):292–306.CrossRefPubMedGoogle Scholar
  54. 54.
    Ginestier C, Wicinski J, Cervera N, Monville F, Finetti P, Bertucci F, et al. Retinoid signaling regulates breast cancer stem cell differentiation. Cell Cycle. 2009;8(20):3297–302.CrossRefPubMedCentralPubMedGoogle Scholar
  55. 55.
    Luo P, Wang A, Payne KJ, Peng H, Wang J, Parrish YK, et al. Intrinsic retinoic acid receptor alpha-cyclin-dependent kinase-activating kinase signaling involves coordination of the restricted proliferation and granulocytic differentiation of human hematopoietic stem cells. Stem Cells. 2007;25(10):2628–37.CrossRefPubMedGoogle Scholar
  56. 56.
    Duester G, Mic FA, Molotkov A. Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Chem Biol Interact. 2003;143–144:201–10.CrossRefPubMedGoogle Scholar
  57. 57.
    Hilton J. Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia. Cancer Res. 1984;44(11):5156–60.PubMedGoogle Scholar
  58. 58.
    Kastan MB, Schlaffer E, Russo JE, Colvin OM, Civin CI, Hilton J. Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells. Blood. 1990;75(10):1947–50.PubMedGoogle Scholar
  59. 59.
    Jones RJ, Barber JP, Vala MS, Collector MI, Kaufmann SH, Ludeman SM, et al. Assessment of aldehyde dehydrogenase in viable cells. Blood. 1995;85(10):2742–6.PubMedGoogle Scholar
  60. 60.
    Storms RW, Trujillo AP, Springer JB, Shah L, Colvin OM, Ludeman SM, et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci U S A. 1999;96(16):9118–23.CrossRefPubMedCentralPubMedGoogle Scholar
  61. 61.
    Vaidyanathan G, Song H, Affleck D, McDougald DL, Storms RW, Zalutsky MR, et al. Targeting aldehyde dehydrogenase: a potential approach for cell labeling. Nucl Med Biol. 2009;36(8):919–29.CrossRefPubMedCentralPubMedGoogle Scholar
  62. 62.
    Rasper M, Schäfer A, Piontek G, Teufel J, Brockhoff G, Ringel F, et al. Aldehyde dehydrogenase 1 positive glioblastoma cells show brain tumor stem cell capacity. Neuro Oncol. 2010;12(10):1024–33.CrossRefPubMedCentralPubMedGoogle Scholar
  63. 63.
    Mao P, Joshi K, Li J, Kim S-H, Li P, Santana-Santos L, et al. Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3. Proc Natl Acad Sci U S A. 2013;110(21):8644–9.CrossRefPubMedCentralPubMedGoogle Scholar
  64. 64.
    Zhang W, Yan W, You G, Bao Z, Wang Y, Liu Y, et al. Genome-wide DNA methylation profiling identifies ALDH1A3 promoter methylation as a prognostic predictor in G-CIMP-primary glioblastoma. Cancer Lett. 2013;328(1):120–5.CrossRefPubMedGoogle Scholar
  65. 65.
    Liu D-Y, Ren C-P, Yuan X-R, Zhang L-H, Liu J, Liu Q, et al. ALDH1 expression is correlated with pathologic grade and poor clinical outcome in patients with astrocytoma. J Clin Neurosci. 2012;19(12):1700–5.CrossRefPubMedGoogle Scholar
  66. 66.
    Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140(1):62–73.CrossRefPubMedGoogle Scholar
  67. 67.
    Dembinski JL, Krauss S. Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis. 2009;26(7):611–23.CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell. 2010;141(4):583–94.CrossRefPubMedCentralPubMedGoogle Scholar
  69. 69.
    Deleyrolle LP, Harding A, Cato K, Siebzehnrubl FA, Rahman M, Azari H, et al. Evidence for label-retaining tumour-initiating cells in human glioblastoma. Brain J Neurol. 2011;134(Pt 5):1331–43.CrossRefGoogle Scholar
  70. 70.
    Krafft C, Sobottka SB, Geiger KD, Schackert G, Salzer R. Classification of malignant gliomas by infrared spectroscopic imaging and linear discriminant analysis. Anal Bioanal Chem. 2007; 387(5):1669–77.CrossRefPubMedGoogle Scholar
  71. 71.
    Krafft C, Thümmler K, Sobottka SB, Schackert G, Salzer R. Classification of malignant gliomas by infrared spectroscopy and linear discriminant analysis. Biopolymers. 2006;82(4):301–5.CrossRefPubMedGoogle Scholar
  72. 72.
    Steiner G, Küchler S, Hermann A, Koch E, Salzer R, Schackert G, et al. Rapid and label-free classification of human glioma cells by infrared spectroscopic imaging. Cytometry A. 2008;73A(12):1158–64.CrossRefPubMedGoogle Scholar
  73. 73.
    Wehbe K, Pineau R, Eimer S, Vital A, Loiseau H, Déléris G. Differentiation between normal and tumor vasculature of animal and human glioma by FTIR imaging. Analyst. 2010;135(12):3052–9.CrossRefPubMedGoogle Scholar
  74. 74.
    Uckermann O, Galli R, Anger M, Herold-Mende C, Koch E, Schackert G, et al. Label-free identification of the glioma stem-like cell fraction using Fourier-transform infrared spectroscopy. Int J Radiat Biol. 2014;90:710–7.CrossRefPubMedGoogle Scholar
  75. 75.
    Reynolds BA, Rietze RL. Neural stem cells and neurospheres: re-evaluating the relationship. Nat Methods. 2005;2(5):333–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Vescovi AL, Galli R, Reynolds BA. Brain tumour stem cells. Nat Rev Cancer. 2006;6(6):425–36.CrossRefPubMedGoogle Scholar
  77. 77.
    Hermann A, Maisel M, Liebau S, Gerlach M, Kleger A, Schwarz J, et al. Mesodermal cell types induce neurogenesis from adult human hippocampal progenitor cells. J Neurochem. 2006;98(2):629–40.CrossRefPubMedGoogle Scholar
  78. 78.
    Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia. 2002;39(3):193–206.CrossRefPubMedGoogle Scholar
  79. 79.
    Gritti A, Galli R, Vescovi AL. Clonal analyses and cryopreservation of neural stem cell cultures. Methods Mol Biol. 2008;438:173–84.CrossRefPubMedGoogle Scholar
  80. 80.
    Pavon LF, Marti LC, Sibov TT, Malheiros SMF, Brandt RA, Cavalheiro S, et al. In vitro analysis of neurospheres derived from glioblastoma primary culture: a novel methodology paradigm. Front Neurol. 2014;4:214.PubMedCentralPubMedGoogle Scholar
  81. 81.
    Gritti A, Frölichsthal-Schoeller P, Galli R, Parati EA, Cova L, Pagano SF, et al. Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci. 1999; 19(9):3287–97.PubMedGoogle Scholar
  82. 82.
    Singec I, Knoth R, Meyer RP, Maciaczyk J, Volk B, Nikkhah G, et al. Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biology. Nat Methods. 2006;3(10):801–6.CrossRefPubMedGoogle Scholar
  83. 83.
    Parker MA, Anderson JK, Corliss DA, Abraria VE, Sidman RL, Park KI, et al. Expression profile of an operationally-defined neural stem cell clone. Exp Neurol. 2005;194(2):320–32.CrossRefPubMedGoogle Scholar
  84. 84.
    Suslov ON, Kukekov VG, Ignatova TN, Steindler DA. Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc Natl Acad Sci U S A. 2002;99(22):14506–11.CrossRefPubMedCentralPubMedGoogle Scholar
  85. 85.
    Kukekov VG, Laywell ED, Thomas LB, Steindler DA. A nestin-negative precursor cell from the adult mouse brain gives rise to neurons and glia. Glia. 1997;21(4):399–407.CrossRefPubMedGoogle Scholar
  86. 86.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.CrossRefPubMedGoogle Scholar
  87. 87.
    Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3(12):895–902.CrossRefPubMedGoogle Scholar
  88. 88.
    Dick JE. Breast cancer stem cells revealed. Proc Natl Acad Sci U S A. 2003;100(7):3547–9.CrossRefPubMedCentralPubMedGoogle Scholar
  89. 89.
    Tysnes BB. Tumor-initiating and -propagating cells: cells that we would like to identify and control. Neoplasia. 2010;12(7):506–15.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 2004;64(19):7011–21.CrossRefPubMedGoogle Scholar
  91. 91.
    Choi SA, Lee JY, Phi JH, Wang K-C, Park C-K, Park S-H, et al. Identification of brain tumour initiating cells using the stem cell marker aldehyde dehydrogenase. Eur J Cancer. 2014;50(1):137–49.CrossRefPubMedGoogle Scholar
  92. 92.
    Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A. Tumor growth need not be driven by rare cancer stem cells. Science. 2007;317(5836):337.CrossRefPubMedGoogle Scholar
  93. 93.
    Dovey MC, Zon LI. Defining cancer stem cells by xenotransplantation in zebrafish. Methods Mol Biol. 2009;568:1–5.CrossRefPubMedGoogle Scholar
  94. 94.
    Yang X-J, Cui W, Gu A, Xu C, Yu S-C, Li T-T, et al. A novel zebrafish xenotransplantation model for study of glioma stem cell invasion. PLoS One. 2013;8(4):e61801.CrossRefPubMedCentralPubMedGoogle Scholar
  95. 95.
    White RM, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, et al. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell. 2008;2(2):183–9.CrossRefPubMedCentralPubMedGoogle Scholar
  96. 96.
    Taylor AM, Zon LI. Zebrafish tumor assays: the state of transplantation. Zebrafish. 2009;6(4):339–46.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Section of NeurosurgeryGeisel School of Medicine at DartmouthLebanonUSA
  2. 2.Department of Neurological SurgeryVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations