Cancer stem cells in solid tumors: Elusive or illusive?

Cell Communication and Signaling

Volumn 8, Issue , 2010, Pages

  Welte, Yvonne ^a   Adjaye, James ^a   Lehrach, Hans R ^a   Regenbrecht, Christian R A ^a,b  

^a MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77951946973     PISSN: None     EISSN: 1478811X     Source Type: Journal    
DOI: 10.1186/1478-811X-8-6     Document Type: Review

References (94)

1. R Virchow, Die Cellularpathologie in ihrer Begrundung auf physiologische und pathologische Gewebelehre Berlin: August Hirschwald 1858
2. The role of tumor stem-cells in regrowth of the tumor following drastic applications. S Makino, Acta Unio Int Contra Cancrum 1959 15 Suppl 1 196 198 14420161
3. Primary bioassay of human myeloma stem cells. A Hamburger, SE Salmon, J Clin Invest 1977 60 846 854 10.1172/JCI108839 302265
4. Primary bioassay of human tumor stem cells. AW Hamburger, SE Salmon, Science 1977 197 461 463 10.1126/science.560061 560061
5. Mouse myeloma tumor stem cells: a primary cell culture assay. CH Park, DE Bergsagel, EA McCulloch, J Natl Cancer Inst 1971 46 411 422 5115909
6. Stem cells, cancer, and cancer stem cells. T Reya, SJ Morrison, MF Clarke, IL Weissman, Nature 2001 414 105 111 10.1038/35102167 11689955
7. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. E Monzani, F Facchetti, E Galmozzi, E Corsini, A Benetti, C Cavazzin, A Gritti, A Piccinini, D Porro, M Santinami, et al. Eur J Cancer 2007 43 935 946 10.1016/j.ejca.2007.01.017 17320377
8. Keratinocyte stem cells: targets for cutaneous carcinogens. RJ Morris, J Clin Invest 2000 106 3 8 10.1172/JCI10508 10880041
9. Wnt signalling in stem cells and cancer. T Reya, H Clevers, Nature 2005 434 843 850 10.1038/nature03319 15829953
10. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. J Lessard, G Sauvageau, Nature 2003 423 255 260 10.1038/nature01572 12714970
11. Stemming Cancer: Functional Genomics of Cancer Stem Cells in Solid Tumors. CR Regenbrecht, H Lehrach, J Adjaye, Stem Cell Rev 2008 4 4 319 28 10.1007/s12015-008-9034-0 18561035
12. Efficient tumour formation by single human melanoma cells. E Quintana, M Shackleton, MS Sabel, DR Fullen, TM Johnson, SJ Morrison, Nature 2008 456 593 598 10.1038/nature07567 19052619
13. CD133+ cell selection is an alternative to CD34+ cell selection for ex vivo expansion of hematopoietic stem cells. L Kobari, MC Giarratana, F Pflumio, B Izac, L Coulombel, L Douay, J Hematother Stem Cell Res 2001 10 273 281 10.1089/15258160151134980 11359674
14. Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. N Quirici, D Soligo, L Caneva, F Servida, P Bossolasco, GL Deliliers, Br J Haematol 2001 115 186 194 10.1046/j.1365-2141.2001.03077.x 11722432
15. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells. CV Pfenninger, T Roschupkina, F Hertwig, D Kottwitz, E Englund, J Bengzon, SE Jacobsen, UA Nuber, Cancer Res 2007 67 5727 5736 10.1158/0008-5472.CAN-07-0183 17575139
16. The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. D Corbeil, K Roper, A Hellwig, M Tavian, S Miraglia, SM Watt, PJ Simmons, B Peault, DW Buck, WB Huttner, J Biol Chem 2000 275 5512 5520 10.1074/jbc.275.8.5512 10681530
17. Identification of human brain tumour initiating cells. SK Singh, C Hawkins, ID Clarke, JA Squire, J Bayani, T Hide, RM Henkelman, MD Cusimano, PB Dirks, Nature 2004 432 396 401 10.1038/nature03128 15549107
18. Biological and genetic characteristics of tumor-initiating cells in colon cancer. K Ieta, F Tanaka, N Haraguchi, Y Kita, H Sakashita, K Mimori, T Matsumoto, H Inoue, H Kuwano, M Mori, Ann Surg Oncol 2008 15 638 648 10.1245/s10434-007-9605-3 17932721
19. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. G Bertolini, L Roz, P Perego, M Tortoreto, E Fontanella, L Gatti, G Pratesi, A Fabbri, F Andriani, S Tinelli, et al. Proc Natl Acad Sci USA 2009 106 16281 16286 10.1073/pnas.0905653106 19805294
20. Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. M Florek, M Haase, AM Marzesco, D Freund, G Ehninger, WB Huttner, D Corbeil, Cell Tissue Res 2005 319 15 26 10.1007/s00441-004-1018-z 15558321
21. Increased expression of stem cell markers in malignant melanoma. WM Klein, BP Wu, S Zhao, H Wu, AJ Klein-Szanto, SR Tahan, Mod Pathol 2007 20 102 107 10.1038/modpathol.3800720 17143262
22. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. W Song, H Li, K Tao, R Li, Z Song, Q Zhao, F Zhang, K Dou, Int J Clin Pract 2008 62 1212 1218 10.1111/j.1742-1241.2008.01777.x 18479363
23. Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer. Q Wang, ZG Chen, CZ Du, HW Wang, L Yan, J Gu, Histopathology 2009 55 284 293 10.1111/j.1365-2559.2009.03378.x 19723143
24. Expression of stem cell markers in circulating melanoma cells. A Fusi, A Busse, S Ochsenreiter, A Rietz, U Keilholz, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition), (May 20 Supplement): J Clin Oncol 2009 27 No 15S 22056
25. Dormancy of metastatic melanoma. L Ossowski, JA Aguirre-Ghiso, Pigment Cell Melanoma Res 2010 23 1 41 56 Epub 2009 Oct 19 10.1111/j.1755-148X.2009. 00647.x 19843243
26. Isolation of multipotent adult stem cells from the dermis of mammalian skin. JG Toma, M Akhavan, KJ Fernandes, F Barnabe-Heider, A Sadikot, DR Kaplan, FD Miller, Nat Cell Biol 2001 3 778 784 10.1038/ncb0901-778 11533656
27. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. BA Reynolds, S Weiss, Science 1992 255 1707 1710 10.1126/science.1553558 1553558
28. Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines. M Jaksch, J Munera, R Bajpai, A Terskikh, RG Oshima, Cancer Res 2008 68 7882 7886 10.1158/0008-5472.CAN-08-0723 18829544
29. Cell cycle analysis of the CD133+ and CD133- cells isolated from umbilical cord blood. B Grskovic, K Ruzicka, A Karimi, D Qujeq, MM Muller, Clin Chim Acta 2004 343 173 178 10.1016/j.cccn.2004.01.023 15115691
30. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. G Liu, X Yuan, Z Zeng, P Tunici, H Ng, IR Abdulkadir, L Lu, D Irvin, KL Black, JS Yu, Mol Cancer 2006 5 67 10.1186/1476-4598-5-67 17140455
31. Detection and characterization of CD133+ cancer stem cells in human solid tumours. V Tirino, V Desiderio, R d'Aquino, F De Francesco, G Pirozzi, A Graziano, U Galderisi, C Cavaliere, A De Rosa, G Papaccio, A Giordano, PLoS ONE 2008 3 3469 10.1371/journal.pone.0003469 18941626
32. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. G Rappa, O Fodstad, A Lorico, Stem Cells 2008 26 3008 3017 10.1634/stemcells.2008-0601 18802032
33. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. U Gat, R DasGupta, L Degenstein, E Fuchs, Cell 1998 95 605 614 10.1016/S0092-8674(00)81631-1 9845363
34. Wnt signalling and cancer stem cells. J Espada, MB Calvo, S Diaz-Prado, V Medina, Clin Transl Oncol 2009 11 411 427 10.1007/s12094-009-0380-4 19574199
35. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. V Korinek, N Barker, P Moerer, E van Donselaar, G Huls, PJ Peters, H Clevers, Nat Genet 1998 19 379 383 10.1038/1270 9697701
36. The Hedgehog and Wnt signalling pathways in cancer. J Taipale, PA Beachy, Nature 2001 411 349 354 10.1038/35077219 11357142
37. The WNT/Beta-catenin pathway in melanoma. L Larue, V Delmas, Front Biosci 2006 11 733 742 10.2741/1831 16146765
38. CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. J Wang, PO Sakariassen, O Tsinkalovsky, H Immervoll, SO Boe, A Svendsen, L Prestegarden, G Rosland, F Thorsen, L Stuhr, et al. Int J Cancer 2008 122 761 768 10.1002/ijc.23130 17955491
39. Detection of cancer stem cells from the C6 glioma cell line. XD Zhou, XY Wang, FJ Qu, YH Zhong, XD Lu, P Zhao, DH Wang, QB Huang, L Zhang, XG Li, J Int Med Res 2009 37 503 510 19383245
40. Most C6 cells are cancer stem cells: evidence from clonal and population analyses. X Zheng, G Shen, X Yang, W Liu, Cancer Res 2007 67 3691 3697 10.1158/0008-5472.CAN-06-3912 17440081
41. Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. G Shen, F Shen, Z Shi, W Liu, W Hu, X Zheng, L Wen, X Yang, In Vitro Cell Dev Biol Anim 2008 44 280 289 10.1007/s11626-008-9115-z 18594936
42. Both CD133+ and CD133- subpopulations of A549 and H446 cells contain cancer-initiating cells. X Meng, M Li, X Wang, Y Wang, D Ma, Cancer Sci 2009 100 1040 1046 10.1111/j.1349-7006.2009.01144.x 19385971
43. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. SV Shmelkov, JM Butler, AT Hooper, A Hormigo, J Kushner, T Milde, R St Clair, M Baljevic, I White, DK Jin, et al. J Clin Invest 2008 118 2111 2120 18497886
44. Identification of cells initiating human melanomas. T Schatton, GF Murphy, NY Frank, K Yamaura, AM Waaga-Gasser, M Gasser, Q Zhan, S Jordan, LM Duncan, C Weishaupt, et al. Nature 2008 451 345 349 10.1038/nature06489 18202660
45. MDR1 expression identifies human melanoma stem cells. GI Keshet, I Goldstein, O Itzhaki, K Cesarkas, L Shenhav, A Yakirevitch, AJ Treves, J Schachter, N Amariglio, G Rechavi, Biochem Biophys Res Commun 2008 368 930 936 10.1016/j.bbrc.2008.02.022 18279661
46. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. L Patrawala, T Calhoun, R Schneider-Broussard, J Zhou, K Claypool, DG Tang, Cancer Res 2005 65 6207 6219 10.1158/0008-5472.CAN-05-0592 16024622
47. SP analysis may be used to identify cancer stem cell populations. A Hadnagy, L Gaboury, R Beaulieu, D Balicki, Exp Cell Res 2006 312 3701 3710 10.1016/j.yexcr.2006.08.030 17046749
48. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. CW Scharenberg, MA Harkey, B Torok-Storb, Blood 2002 99 507 512 10.1182/blood.V99.2.507 11781231
49. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. S Zhou, JJ Morris, Y Barnes, L Lan, JD Schuetz, BP Sorrentino, Proc Natl Acad Sci USA 2002 99 12339 12344 10.1073/pnas.192276999 12218177
50. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. S Zhou, JD Schuetz, KD Bunting, AM Colapietro, J Sampath, JJ Morris, I Lagutina, GC Grosveld, M Osawa, H Nakauchi, BP Sorrentino, Nat Med 2001 7 1028 1034 10.1038/nm0901-1028 11533706
51. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. MA Goodell, K Brose, G Paradis, AS Conner, RC Mulligan, J Exp Med 1996 183 1797 1806 10.1084/jem.183.4.1797 8666936
52. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. C Hirschmann-Jax, AE Foster, GG Wulf, JG Nuchtern, TW Jax, U Gobel, MA Goodell, MK Brenner, Proc Natl Acad Sci USA 2004 101 14228 14233 10.1073/pnas.0400067101 15381773
53. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. T Kondo, T Setoguchi, T Taga, Proc Natl Acad Sci USA 2004 101 781 786 10.1073/pnas.0307618100 14711994
54. Characterization of side population in thyroid cancer cell lines: cancer stem-like cells are enriched partly but not exclusively. N Mitsutake, A Iwao, K Nagai, H Namba, A Ohtsuru, V Saenko, S Yamashita, Endocrinology 2007 148 1797 1803 10.1210/en.2006-1553 17234707
55. Melanoma, a tumor based on a mutant stem cell? JM Grichnik, JA Burch, RD Schulteis, S Shan, J Liu, TL Darrow, CE Vervaert, HF Seigler, J Invest Dermatol 2006 126 142 153 10.1038/sj.jid.5700017 16417230
56. Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. J Wang, LP Guo, LZ Chen, YX Zeng, SH Lu, Cancer Res 2007 67 3716 3724 10.1158/0008-5472.CAN-06-4343 17440084
57. A side population of cells from a human pancreatic carcinoma cell line harbors cancer stem cell characteristics. YH Wang, F Li, B Luo, XH Wang, HC Sun, S Liu, YQ Cui, XX Xu, Neoplasma 2009 56 371 378 10.4149/neo-2009-05-371 19580337
58. Side populations of gastrointestinal cancers are not enriched in stem cells. J Burkert, WR Otto, NA Wright, J Pathol 2008 214 564 573 10.1002/path.2307 18266310
59. Side population does not define stem cell-like cancer cells in the adrenocortical carcinoma cell line NCI h295R. UD Lichtenauer, I Shapiro, K Geiger, M Quinkler, M Fassnacht, R Nitschke, KD Ruckauer, F Beuschlein, Endocrinology 2008 149 1314 1322 10.1210/en.2007-1001 18063677
60. Fluctuation of the SP/non-SP phenotype in the C6 glioma cell line. N Platet, JF Mayol, F Berger, F Herodin, D Wion, FEBS Lett 2007 581 1435 1440 10.1016/j.febslet.2007.02.071 17362939
61. Isolation and characterization of a putative intestinal stem cell fraction from mouse jejunum. CM Dekaney, JM Rodriguez, MC Graul, SJ Henning, Gastroenterology 2005 129 1567 1580 10.1053/j.gastro.2005.08.011 16285956
62. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. PM Chaudhary, IB Roninson, Cell 1991 66 85 94 10.1016/0092-8674(91)90141-K 1712673
63. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. AH Schinkel, JJ Smit, O van Tellingen, JH Beijnen, E Wagenaar, L van Deemter, CA Mol, MA van der Valk, EC Robanus-Maandag, HP te Riele, et al. Cell 1994 77 491 502 10.1016/0092-8674(94)90212-7 7910522
64. A distinct "side population" of cells in human tumor cells: implications for tumor biology and therapy. C Hirschmann-Jax, AE Foster, GG Wulf, MA Goodell, MK Brenner, Cell Cycle 2005 4 203 205 15655356
65. Demystifying SP cell purification: viability, yield, and phenotype are defined by isolation parameters. F Montanaro, K Liadaki, J Schienda, A Flint, E Gussoni, LM Kunkel, Exp Cell Res 2004 298 144 154 10.1016/j.yexcr.2004.04.010 15242769
66. Characterization of a side population of cancer cells from human gastrointestinal system. N Haraguchi, T Utsunomiya, H Inoue, F Tanaka, K Mimori, GF Barnard, M Mori, Stem Cells 2006 24 506 513 10.1634/stemcells.2005-0282 16239320
67. Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation. A Asakura, MA Rudnicki, Exp Hematol 2002 30 1339 1345 10.1016/S0301-472X(02)00954-2 12423688
68. Isolation of cancer stem-like cells from a side population of a human glioblastoma cell line, SK-MG-1. R Fukaya, S Ohta, M Yamaguchi, H Fujii, Y Kawakami, T Kawase, M Toda, Cancer Lett 2010 291 2 150 7 Epub 2009 Nov 13 10.1016/j.canlet.2009.10.010 19913993
69. Characterization of nonmalignant and malignant prostatic stem/progenitor cells by Hoechst side population method. M Mimeault, SK Batra, Methods Mol Biol 2009 568 139 149 full-text 19582424
70. Identifying tumor stem-like cells in mouse melanoma cell lines by analyzing the characteristics of side population cells. J Dou, P Wen, W Hu, Y Li, Y Wu, C Liu, F Zhao, K Hu, J Wang, C Jiang, et al. Cell Biol Int 2009 33 807 815 10.1016/j.cellbi.2009.05.003 19477285
71. Direct identification and enrichment of retinal stem cells/progenitors by Hoechst dye efflux assay. S Bhattacharya, JD Jackson, AV Das, WB Thoreson, C Kuszynski, J James, S Joshi, I Ahmad, Invest Ophthalmol Vis Sci 2003 44 2764 2773 10.1167/iovs.02-0899 12766085
72. Cell cycle specific toxicity of the Hoechst 33342 stain in untreated or irradiated murine tumor cells. DW Siemann, PC Keng, Cancer Res 1986 46 3556 3559 3708586
73. Side population cells in human cancers. C Wu, BA Alman, Cancer Lett 2008 268 1 9 10.1016/j.canlet.2008.03.048 18487012
74. Microfluorometric study of oxygen dependence of (1"-pyrene butyl)-2-rhodamine ester probe in mitochondria of living cells. AC Ribou, J Vigo, E Kohen, JM Salmon, J Photochem Photobiol B 2003 70 107 115 10.1016/S1011-1344(03)00072-1 12849701
75. The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models. C Martin, J Walker, A Rothnie, R Callaghan, Br J Cancer 2003 89 1581 1589 10.1038/sj.bjc.6601300 14562035
76. Construction of a model cell line for the assay of MDR1 (multi drug resistance gene-1) substrates/inhibitors using HeLa cells. F Kugawa, T Suzuki, M Miyata, K Tomono, F Tamanoi, Pharmazie 2009 64 296 300 19530439
77. Replacing Hoechst33342 with Rhodamine123 in isolation of cancer stem-like cells from the MHCC97 cell line. WH Liu, NS Qian, R Li, KF Dou, Toxicol In Vitro 2010 24 2 538 45 Epub 2009 Nov 12 10.1016/j.tiv.2009.11.008 19913610
78. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. PP Szotek, R Pieretti-Vanmarcke, PT Masiakos, DM Dinulescu, D Connolly, R Foster, D Dombkowski, F Preffer, DT Maclaughlin, PK Donahoe, Proc Natl Acad Sci USA 2006 103 11154 11159 10.1073/pnas.0603672103 16849428
79. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. T Chiba, K Kita, YW Zheng, O Yokosuka, H Saisho, A Iwama, H Nakauchi, H Taniguchi, Hepatology 2006 44 240 251 10.1002/hep.21227 16799977
80. Identification and expansion of human colon-cancer-initiating cells. L Ricci-Vitiani, DG Lombardi, E Pilozzi, M Biffoni, M Todaro, C Peschle, R De Maria, Nature 2007 445 111 115 10.1038/nature05384 17122771
81. A tumorigenic subpopulation with stem cell properties in melanomas. D Fang, TK Nguyen, K Leishear, R Finko, AN Kulp, S Hotz, PA Van Belle, X Xu, DE Elder, M Herlyn, Cancer Res 2005 65 9328 9337 10.1158/0008-5472.CAN-05-1343 16230395
82. Matrigel: basement membrane matrix with biological activity. HK Kleinman, GR Martin, Semin Cancer Biol 2005 15 378 386 10.1016/j.semcancer.2005.05.004 15975825
83. Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? MJ Bissell, MA Labarge, Cancer Cell 2005 7 17 23 15652746
84. Tumor growth need not be driven by rare cancer stem cells. PN Kelly, A Dakic, JM Adams, SL Nutt, A Strasser, Science 2007 317 337 10.1126/science. 1142596 17641192
85. The effect of lethally irradiated cells on the transplantability of murine tumours. HB Hewitt, E Blake, EH Proter, Br J Cancer 1973 28 123 135 4730176
86. Identifying cancer stem cells in solid tumors: case not proven. RP Hill, Cancer Res 2006 66 1891 1895 10.1158/0008-5472.CAN-05-3450 16488984
87. Antitumor immunity and cancer stem cells. T Schatton, MH Frank, Ann N Y Acad Sci 2009 1176 154 169 10.1111/j.1749-6632.2009.04568.x 19796244
88. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. K Takahashi, S Yamanaka, Cell 2006 126 663 676 10.1016/j.cell.2006.07.024 16904174
89. Dissecting direct reprogramming through integrative genomic analysis. TS Mikkelsen, J Hanna, X Zhang, M Ku, M Wernig, P Schorderet, BE Bernstein, R Jaenisch, ES Lander, A Meissner, Nature 2008 454 49 55 10.1038/nature07056 18509334
90. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. D Huangfu, R Maehr, W Guo, A Eijkelenboom, M Snitow, AE Chen, DA Melton, Nat Biotechnol 2008 26 795 797 10.1038/nbt1418 18568017
91. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. M Wernig, CJ Lengner, J Hanna, MA Lodato, E Steine, R Foreman, J Staerk, S Markoulaki, R Jaenisch, Nat Biotechnol 2008 26 916 924 10.1038/nbt1483 18594521
92. Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. CA Lyssiotis, RK Foreman, J Staerk, M Garcia, D Mathur, S Markoulaki, J Hanna, LL Lairson, BD Charette, LC Bouchez, et al. Proc Natl Acad Sci USA 2009 106 8912 8917 10.1073/pnas.0903860106 19447925
93. Cancer stem cells: mirage or reality? PB Gupta, CL Chaffer, RA Weinberg, Nat Med 2009 15 1010 1012 10.1038/nm0909-1010 19734877
94. Current progress and prospects of induced pluripotent stem cells. L Chen, L Liu, Sci China C Life Sci 2009 52 622 636 10.1007/s11427-009-0092-6 19641867