Induced pluripotent stem cells: Applications in regenerative medicine, disease modeling, and drug discovery

Frontiers in Cell and Developmental Biology

Volumn 3, Issue FEB, 2015, Pages

  Singh, Vimal K ^a   Kalsan, Manisha ^a   Kumar, Neeraj ^a   Saini, Abhishek ^a   Chandra, Ramesh ^b  

^a DELHI TECHNOLOGICAL UNIVERSITY   (India)

^b UNIVERSITY OF DELHI   (India)

Author keywords

Differentiation; Disease modeling; Drug discovery; Gene therapy; IPSC; Pluripotency; Reprogramming

Indexed keywords

EID: 85051604758     PISSN: None     EISSN: 2296634X     Source Type: Journal    
DOI: 10.3389/fcell.2015.00002     Document Type: Review

References (139)

1. Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., et al. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat. Biotechnol. 26, 1276-1284. doi: 10.1038/nbt.1503
2. Adewumi, O., Aflatoonian, B., Ahrlund-Richter, L., Amit, M., Andrews, P. W., Beighton, G., et al. (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat. Biotechnol. 25, 803-816. doi: 10.1038/nbt1318
3. Amenduni, M., De Filippis, R., Cheung, A. Y. L., Disciglio, V., Epistolato, M. C., Ariani, F., et al. (2011). iPS cells to model CDKL5-related disorders. Eur. J. Hum. Genet. 19, 1246-1255. doi: 10.1038/ejhg.2011
4. Asai, Y., Tada, M., Otsuji, T. G., and Nakatsuji, N. (2010). Combination of functional cardiomyocytes derived from human stem cells and a highly-efficient microelectrode array system: an ideal hybrid model assay for drug development. Curr. Stem Cell Res. Ther. 5, 227-232. doi: 10.2174/157488810791824502
5. Bahadduri, P. M., Polli, J. E., Swaan, P. W., and Ekins, S. (2010). Targeting drug transporters-combining in silico and in vitro approaches to predict in vivo. Methods Mol. Biol. 637, 65-103. doi: 10.1007/978-1-60761-700-6_4
6. Batista, L. F., Pech, M. F., Zhong, M. F., Nguyen, H. N., Xie, K. T., Zaug, A. J., et al. (2011). Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474, 399-402. doi: 10.1038/nature10084
7. Brambrink, T., Foreman, R., Welstead, G. G., Lengner, C. J., Wernig, M., Suh, H., et al. (2008). Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2, 151-159. doi: 10.1016/j.stem.2008.01.004
8. Briggs, J. A., Mason, E. A., Ovchinnikov, D. A., Wells, C. A., and Wolvetang, E. J. (2013). Concise review: new paradigms for down syndrome research using induced pluripotent stem cells: tackling complex human genetic disease. Stem Cells Transl. Med. 2, 175-184. doi: 10.5966/sctm.2012-0117
9. Campuzano, V., Montermini, L., Molto, M. D., Pianese, L., Cossee, M., Cavalcanti, F., et al. (1996). Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271, 1423-1427. doi: 10.1126/science.271.5254.1423
10. Cao, F., Wagner, R. A., Wilson, K. D., Xie, X., Fu, J. D., Drukker, M., et al. (2008). Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS ONE 3:e3474. doi: 10.1371/journal.pone.0003474
11. Carvajal-Vergara, X., Sevilla, A., D'Souza, S. L., Ang, Y. S., Schaniel, C., Lee, D. F., et al. (2010). Patient-specifi c induced pluripotent stem-cell derived models of LEOPARD syndrome. Nature 465, 808-812. doi: 10.1038/nature09005
12. Cheng, K. W., Agarwal, R., Mitra, S., and Mills, G. B. (2013). Rab25 small GTPase mediates secretion of tumor necrosis factor receptor superfamily member 11b (osteoprotegerin) protecting cancer cells from effects of TRAIL. J. Genet. Syndr. Gene Ther. 4:153. doi: 10.4172/2157-7412.1000153
13. Chestkov, I. V., Vasilieva, E. A., Illarioshkin, S. N., Lagarkova, M. A., and Kiselev, S. L. (2014). Patient-specific induced pluripotent stem cells for SOD1-associated amyotrophic lateral sclerosis pathogenesis studies. Acta Naturae 6, 54-60
14. Choi, M. S., Kim, Y., Shim, J. S., Park, J. T., Wang, R., Leach, S. D., et al. (2013). Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology 57, 2458-2468. doi: 10.1002/hep.26237
15. Chun, Y. S., Byun, K., and Lee, B. (2011). Induced pluripotent stem cells and personalized medicine: current progress and future perspectives. Anat. Cell Biol. 44, 245-255. doi: 10.5115/acb.2011.44.4.245
16. Desnuelle, C., Dib, M., Garrel, C., and Favier, A. (2001). A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2, 9-18. doi: 10.1080/146608201300079364
17. Devine, M. J., Ryten, M., Vodicka, P., Thomson, A. J., Burdon, T., Houlden, H., et al. (2011). Parkinson's disease induced pluripotent stem cells with triplication of the a-synuclein locus. Nat. Commun. 2, 440. doi: 10.1038/ncomms1453
18. Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218-1221. doi: 10.1126/science.1158799
19. Doherty, A. M., and Fisher, E. M. (2003). Microcell-mediated chromosome transfer (MMCT): small cells with huge potential. Mamm. Genome 14, 583-592. doi: 10.1007/s00335-003-4002-0
20. Ebert, A. D., Yu, J., Rose, F. F. Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., et al. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277-280. doi: 10.1038/nature07677
21. Evans, M. J., and Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156. doi: 10.1038/292154a0
22. Farra, N., Zhang, W. B., Pasceri, P., Eubanks, J. H., Salter, M. W., and Ellis, J. (2012). Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations. Mol. Psychiatry 17, 1261-1271. doi: 10.1038/mp.2011.180
23. Feng, B., Jiang, J., Kraus, P., Ng, J. H., Heng, J. C., Chan, Y. S., et al. (2009). Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat. Cell Biol. 11, 197-203. doi: 10.1038/ncb1827
24. Filareto, A., Parker, S., Darabi, R., Borges, L., Iacovino, M., Schaaf, T., et al. (2013). An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells. Nat. Commun. 4, 1549. doi: 10.1038/ncomms2550
25. Fong, H., Wang, C., Knoferle, J., Walker, D., Balestra, M. E., and Tong, L. M. (2013). Genetic correction of tauopathy phenotypes in neurons derived from human induced pluripotent stem cells. Stem Cell Reports 1, 226-234. doi: 10.1016/j.stemcr.2013.08.001
26. Fong, Y. W., Inouye, C., Yamaguchi, T., Cattoglio, C., Grubisic, I., and Tjian, R. (2011). A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells. Cell 147, 120-131. doi: 10.1016/j.cell.2011.08.038
27. Fusaki, N., Ban, H., Nishiyama, A., Saeki, K., and Hasegawa, M. (2009). Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 85, 348-362. doi: 10.2183/pjab.85.348
28. Gangopadhyay, S. B., Sherratt, T. G., Heckmatt, J. Z., Dubowitz, V., Miller, G., Shokeir, M., et al. (1992). Dystrophin in frameshift deletion patients with Becker muscular dystrophy. Am. J. Hum. Genet. 51, 562-570
29. Ghaleb, A. M., Nandan, M. O., Chanchevalap, S., Dalton, W. B., Hisamuddin, I. M., and Yang, V. W. (2005). Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation. Cell Res. 15, 92-96. doi: 10.1038/sj.cr.7290271
30. Gonzalez, F., Barragan Monasterio, M., Tiscornia, G., Montserrat Pulido, N., Vassena, R., Batlle Morera, L., et al. (2009). Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector. Proc. Natl. Acad. Sci. U.S.A. 106, 8918-8922. doi: 10.1073/pnas.0901471106
31. Grizot, S., Smith, J., Daboussi, F., Prieto, J., Redondo, P., Merino, N., et al. (2009). Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease. Nucleic Acids Res. 37, 5405-5419. doi: 10.1093/nar/gkp548
32. Groeneveld, G. J., Veldink, J. H., van der Tweel, I., Kalmijn, S., Beijer, C., de Visser, M., et al. (2003). A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann. Neurol. 53, 437-445. doi: 10.1002/ana.10554
33. Guha, P., Morgan, J. W., Mostoslavsky, G., Rodrigues, N. P., and Boyd, A. S. (2013). Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell 12, 407-412. doi: 10.1016/j.stem.2013.01.006
34. Gunaseeli, I., Doss, M. X., Antzelevitch, C., Hescheler, J., and Sachinidis, A. (2010). Induced pluripotent stem cells as a model for accelerated patient-and disease-specific drug discovery. Curr. Med. Chem. 17, 759-766. doi: 10.2174/092986710790514480
35. Gurdon, J. B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J. Embryol. Exp. Morphol. 10, 622-640
36. Haase, A., Olmer, R., Schwanke, K., Wunderlich, S., Merkert, S., Hess, C., et al. (2009). Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5, 434-441. doi: 10.1016/j.stem.2009.08.021
37. Hanna, J., Markoulaki, S., Schorderet, P., Carey, B. W., Beard, C., Wernig, M., et al. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133, 250-264. doi: 10.1016/j.cell.2008.03.028
38. Hochedlinger, K., and Jaenisch, R. (2002). Nuclear transplantation: lessons from frogs and mice. Curr. Opin. Cell Biol. 14, 741-748. doi: 10.1016/S0955-0674(02)00380-0
39. Hochedlinger, K., Yamada, Y., Beard, C., and Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465-477. doi: 10.1016/j.cell.2005.02.018
40. Hockemeyer, D., Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., et al. (2009). Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat. Biotechnol. 27, 851-857. doi: 10.1038/nbt.1562
41. Hockemeyer, D., Wang, H., Kiani, S., Lai, C. S., Gao, Q., Cassady, J. P., et al. (2011). Genetic engineering of human pluripotent cells using TALE nucleases. Nat. Biotechnol. 29, 731-734. doi: 10.1038/nbt.1927
42. Howe, S. J., Mansour, M. R., Schwarzwaelder, K., Bartholomae, C., Hubank, M., Kempski, H., et al. (2008). Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J. Clin. Invest. 118, 3143-3150. doi: 10.1172/JCI35798
43. Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E., et al. (2008a). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol. 26, 795-797. doi: 10.1038/nbt1418
44. Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., et al. (2008b). Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol. 26, 1269-1275. doi: 10.1038/nbt.1502
45. Hurtado-Lorenzo, A., Millan, E., Gonzalez-Nicolini, V., Suwelack, D., Castro, M. G., and Lowenstein, P. R. (2004). Differentiation and transcription factor gene therapy in experimental Parkinson's disease: sonic hedgehog and Gli-1, but Not Nurr-1, protect nigrostriatal cell bodies from 6-OHDA-induced neurodegeneration. Mol. Ther. 10, 507-524. doi: 10.1016/j.ymthe.2004.05.021
46. Israel, M. A., Yuan, S. H., Bardy, C., Reyna, S. M., Mu, Y., Herrera, C., et al. (2012). Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 482, 216-220. doi: 10.1038/nature10821
47. Jiang, Y., Cowley, S. A., Siler, U., Melguizo, D., Tilgner, K., Browne, C., et al. (2012). Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous disease. Stem Cells 30, 599-611. doi: 10.1002/stem.1053
48. Kaitin, K. I. (2008). Obstacles and opportunities in new drug development. Clin. Pharmacol. Ther. 83, 210-212. doi: 10.1038/sj.clpt.6100462
49. Kaye, J. A., and Finkbeiner, S. (2013). Modeling Huntington's disease with induced pluripotent stem cells. Mol. Cell. Neurosci. 56, 50-64. doi: 10.1016/j.mcn.2013.02.005
50. Kazuki, Y., Hiratsuka, M., Takiguchi, M., Osaki, M., Kajitani, M., Hoshiya, H., et al. (2009). Complete genetic correction of iPS cells from Duchenne muscular dystrophy. Am. Soc. Gene Cell Ther. 18, 386-393. doi: 10.1038/mt.2009.274
51. Kerns, W. D., Pavkov, K. L., Donofrio, D. J., Gralla, E. J., and Swenberg, J. A. (1983). Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res. 43, 4382-4392
52. Khan, I. F., Hirata, R. K., Wang, P. R., Li, Y., Kho, J., Nelson, A., et al. (2010). Engineering of human pluripotent stem cells by AAV-mediated gene targeting. Mol. Ther. 18, 1192-1199. doi: 10.1038/mt.2010.55
53. Kim, D., Kim, C. H., Moon, J. I., Chung, Y. G., Chang, M. Y., Han, B. S., et al. (2009b). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4, 472-476. doi: 10.1016/j.stem.2009.05.005
54. Kim, J. B., Greber, B., Araúzo-Bravo, M. J., Meyer, J., Park, K. I., Zaehres, H., et al. (2009a). Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649-643. doi: 10.1038/nature08436
55. Kimmel, C. A., and Young, J. F. (1983). Correlating pharmacokinetics and teratogenic endpoints. Fundam. Appl. Toxicol. 3, 250-255. doi: 10.1016/S0272-0590(83)80136-5
56. Klein, C., Nguyen, D., Liu, C. H., Mizoguchi, A., Bhan, A. K., Miki, H., et al. (2003). Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice. Blood 101, 2159-2166. doi: 10.1182/blood-2002-05-1423
57. Ku, S., Soragni, E., Campau, E., Thomas, E. A., Altun, G., Laurent, L. C., et al. (2010). Friedreich's ataxia induced pluripotent stem cells model intergenerational GAATTC triplet repeat instability. Cell Stem Cell 7, 631-637. doi: 10.1016/j.stem.2010.09.014
58. Kunisato, A., Wakatsuki, M., Shinba, H., Ota, T., Ishida, I., Nagao, K., et al. (2011). Direct generation of induced pluripotent stem cells from human nonmobilized blood. Stem Cells Dev. 20, 159-168. doi: 10.1089/scd.2010.0063
59. Kuttler, F., and Mai, S. (2006). c-Myc, genomic instability and disease. Genome Dyn. 1, 171-190. doi: 10.1159/000092507
60. Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., et al. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat. Biotechnol. 25, 1015-1024. doi: 10.1038/nbt1327
61. Lan, M. L., Acharya, M. M., Tran, K. K., Bahari-Kashani, J., Patel, N. H., Strnadel, J., et al. (2012). Characterizing the radioresponse of pluripotent and multipotent human stem cells. PLoS ONE 7:e50048. doi: 10.1371/journal.pone.0050048
62. Laustriat, D., Gide, J., and Peschanski, M. (2010). Human pluripotent stem cells in drug discovery and predictive toxicology. Biochem. Soc. Trans. 38, 1051-1057. doi: 10.1042/BST0381051
63. Lee, G., Papapetrou, E. P., Kim, H., Chambers, S. M., Tomishima, M. J., Fasano, C. A., et al. (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402-406. doi: 10.1038/nature08320
64. Lee, G., and Studer, L. (2011). Modelling familial dysautonomia in human induced pluripotent stem cells. Phil. Trans. R. Soc. B. 366, 2286-2296. doi: 10.1098/rstb.2011.0026
65. Legius, E., Schrander-Stumpel, C., Schollen, E., Pulles-Heintzberger, C., Gewillig, M., and Fryns, J. P. (2002). PTPN11 mutations in LEOPARD syndrome. J. Med. Genet. 39, 571-574. doi: 10.1136/jmg.39.8.571
66. Lei, K., Chen, Y., Chen, H., Wong, L. C., Liu, J., McConkie-Rosell, A., et al. (1995). Genetic basis of glycogen storage disease type 1a: prevalent mutations at the glucose-6-phosphatase locus. Am. J. Hum. Genet. 57, 766-771
67. Levenberg, S., Ferreira, L. S., Chen-Konak, L., Kraehenbuehl, T. P., and Langer, R. (2010). Isolation, differentiation and characterization of vascular cells derived from human embryonic stem cells. Nat. Protoc. 5, 1115-1126. doi: 10.1038/nprot.2010.31
68. Lim, W. F., Inoue-Yokoo, T., Tan, K. S., Lai, I. M., and Sugiyama, D. (2013). Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells. Stem Cell Res. Ther. 4:71. doi: 10.1186/scrt222
69. Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., et al. (2009). Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4, 16-19. doi: 10.1016/j.stem.2008.11.014
70. Li, Y., Tsai, Y., Hsu, C., Erol, D., Yang, J., Wu, W., et al. (2012). Long-term safety and efficacy of human-induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa. Mol. Med. 18:1312-1319. doi: 10.2119/molmed.2012.00242
71. Li, Y., Zhang, Q., Yin, X., Yang, W., Du, Y., Hou, P., et al. (2011). Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res. 21, 196-204. doi: 10.1038/cr.2010.142
72. Liu, G. H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S. L., et al. (2011a). Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472, 221-225. doi: 10.1038/nature09879
73. Liu, H., Kim, Y., Sharkis, S., Marchionni, L., and Jang, Y. (2011b). In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci. Transl. Med. 3, 82ra39. doi: 10.1126/scitranslmed.3002376
74. Liu, H., Ye, Z., Kim, Y. H., Sharkis, S., and Jang, Y. Y. (2010). Generation of endoderm derived human ips cells from primary hepatocytes. Hepatology 51, 1810-1819. doi: 10.1002/hep.23626
75. Maherali, N., Ahfeldt, T., Rigamonti, A., Utikal, J., Cowan, C., and Hochedlinger, K. (2008). A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3, 340-345. doi: 10.1016/j.stem.2008.08.003
76. Mali, P., Ye, Z., Hommond, H. H., Yu, X., Lin, J., Chen, G., et al. (2008). Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts. Stem Cells 26, 1998-2005. doi: 10.1634/stemcells.2008-0346
77. Marson, A., Foreman, R., Chevalier, B., Bilodeau, S., Kahn, M., Young, R. A., et al. (2008). Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell 3, 132-135. doi: 10.1016/j.stem.2008.06.019
78. McNeish, J., Roach, M., Hambor, J., Mather, R. J., Weibley, L., Lazzaro, J., et al. (2010). High throughput screening in embryonic stem cell derived neurons identifies potentiators of a-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate-type glutamate receptors. J. Biol. Chem. 285, 17209-17217. doi: 10.1074/jbc.M109.098814
79. Mikkelsen, T. S., Hanna, J., Zhang, X., Ku, M., Wernig, M., Schorderet, P., et al. (2008). Dissecting direct reprogramming through integrative genomic analysis. Nature 454, 49-55. doi: 10.1038/nature07056
80. Moad, M., Pal, D., Hepburn, A. C., Williamson, S. C., Wilson, L., Lako, M., et al. (2013). A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells. Eur. Urol. 64, 753-761. doi: 10.1016/j.eururo.2013.03.054
81. Nguyen, H. N., Byers, B., Cord, B., Shcheglovitov, A., Byrne, J., Gujar, P., et al. (2011). LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell. 8, 267-280. doi: 10.1016/j.stem.2011.01.013
82. Nori, S., Okada, Y., Yasuda, K., Tsuji, O., Takahashi, Y., Kobayashi, Y., et al. (2011). Human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc. Natl. Acad. Sci. U.S.A. 108, 16825-16830. doi: 10.1073/pnas.1108077108
83. Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317. doi: 10.1038/nature05934
84. Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., and Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949-953. doi: 10.1126/science.1164270
85. Pappas, J. J., and Yang, P. C. (2008). Human ESC vs. iPSC-Pros and Cons. J. Cardiovasc. Trans. Res. 1, 96-99. doi: 10.1007/s12265-008-9032-2
86. Park, E. T., Gum, J. R., Kakar, S., Kwon, S. W., Deng, G., and Kim, Y. S. (2008c). Aberrant expression of SOX2 upregulates MUC5AC gastric foveolar mucin in mucinous cancers of the colorectum and related lesions. Int. J. Cancer 122, 1253-1260. doi: 10.1002/ijc.23225
87. Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., et al. (2008b). Disease-specific induced pluripotent stem cells. Cell 134, 877-886. doi: 10.1016/j.cell.2008.07.041
88. Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., et al. (2008a). Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141-146. doi: 10.1038/nature06534
89. Rashid, S. T., Corbineau, S., Hannan, N., Marciniak, S. J., Miranda, E., Alexander, G., et al. (2010). Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J. Clin. Invest. 120, 3127-3136. doi: 10.1172/JCI43122
90. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62. doi: 10.1038/362059a0
91. Ruiz, S., Brennand, K., Panopoulos, A. D., Herrerias, A., Gage, F. H., and Izpisua-Belmonte, J. C. (2010). High-efficient generation of induced pluripotent stem cells from human astrocytes. PLoS ONE 5:e15526. doi: 10.1371/journal.pone.0015526
92. Sato, T., Joyner, A. L., and Nakamura, H. (2004). How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development? Dev. Growth Differ. 46, 487-494. doi: 10.1111/j.1440-169x.2004.00769.x
93. Sauer, A. V., Morbach, H., Brigida, I., Ng, Y. S., Aiuti, A., and Meffre, E. (2012). Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy. J. Clin. Invest. 122, 2141-2152. doi: 10.1172/JCI61788
94. Seiler, A., Visan, A., Buesen, R., Genschow, E., and Spielmann, H. (2004). Improvement of an in vitro stem cell assay for developmental toxicity: the use of molecular endpoints in the embryonic stem cell test. Reprod. Toxicol. 18, 231-240. doi: 10.1016/j.reprotox.2003.10.015
95. Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., et al. (2010). Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7, 11-14. doi: 10.1016/j.stem.2010.06.003
96. Shefner, J. M., Cudkowicz, M. E., Schoenfeld, D., Conrad, T., Taft, J., Chilton, M., et al. (2004). NEALS Consortium. A clinical trial of creatine in ALS. Neurology 63, 1656-1661. doi: 10.1212/01.WNL.0000142992.81995.F0
97. Shi, Y., Desponts, C., Do, J. T., Hahm, H. S., Scholer, H. R., and Ding, S. (2008a). Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568-574. doi: 10.1016/j.stem.2008.10.004
98. Shi, Y., Do, J. T., Desponts, C., Hahm, H. S., Scholer, H. R., and Ding, S. (2008b). A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525-528. doi: 10.1016/j.stem.2008.05.011
99. Silva, J., Barrandon, O., Nichols, J., Kawaguchi, J., Theunissen, T. W., and Smith, A. (2008). Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol. 6:e253. doi: 10.1371/journal.pbio.0060253
100. Soejitno, A., and Prayudi, P. K. A. (2011). The prospect of induced pluripotent stem cells for diabetes mellitus treatment. Ther. Adv. Endocrinol. Metab. 2, 197-210. doi: 10.1177/2042018811420198
101. Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., et al. (2009). Parkinson's disease patient derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964-977. doi: 10.1016/j.cell.2009.02.013
102. Sollano, J. A., Kirsch, J. M., Bala, M. V., Chambers, M. G., and Harpole, L. H. (2008). The economics of drug discovery and the ultimate valuation of pharmacotherapies in the marketplace. Clin. Pharmacol. Ther. 84, 263-266. doi: 10.1038/clpt.2008.117
103. Somers, A., Jean, J. C., Sommer, C. A., Omari, A., Ford, C. C., Mills, J. A., et al. (2010). Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem Cells 28, 1728-1740. doi: 10.1002/stem.495
104. Song, B., Niclis, J. V., Alikhan, M. A., Sakkal, S., Sylvain, A., Kerr, P. G., et al. (2011). Generation of induced pluripotent stem cells from human kidney mesangial cells. J. Am. Soc. Nephrol. 22, 1213-1220. doi: 10.1681/ASN.2010101022
105. Stadtfeld, M., Maherali, N., Breault, D. T., and Hochedlinger, K. (2008a). Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2, 230-240. doi: 10.1016/j.stem.2008.02.001
106. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., and Hochedlinger, K. (2008b). Induced pluripotent stem cells generated without viral integration. Science 322, 945-949. doi: 10.1126/science.1162494
107. Sugii, S., Kida, Y., Kawamura, T., Suzuki, J., Vassena, R., Yin, Y. Q., et al. (2010). Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proc. Natl. Acad. Sci. U.S.A. 107, 3558-3563. doi: 10.1073/pnas.0910172106
108. Sullivan, G. J., Hay, D. C., Park, I. H., Fletcher, J., Hannoun, Z., Payne, C. M., et al. (2010). Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51, 329-335. doi: 10.1002/hep.23335
109. Suzuki, K., Mitsui, K., Aizawa, E., Hasegawa, K., Kawase, E., Yamagishi, T., et al. (2008). Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors. Proc. Natl. Acad. Sci. U.S.A. 105, 13781-13786. doi: 10.1073/pnas.0806976105
110. Suzuki, N., Yamazaki, S., Yamaguchi, T., Okabe, M., Masaki, H., Takaki, S., et al. (2013). Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. Mol. Ther. 21, 1424-1431. doi: 10.1038/mt.2013.71
111. Tada, M., Takahama, Y., Abe, K., Nakatsuji, N., and Tada, T. (2001). Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol. 11, 1553-1558. doi: 10.1016/S0960-9822(01)00459-6
112. Takahashi, K., Ichisaka, T., and Yamanaka, S. (2006b). Identification of genes involved in tumor-like properties of embryonic stem cells. Methods Mol. Biol. 329, 449-458. doi: 10.1385/1-59745-037-5:449
113. Takahashi, K., and Yamanaka, S. (2006a). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676. doi: 10.1016/j.cell.2006.07.024
114. Tan, Q., Lui, P. P. Y., Rui, Y. F., and Wong, Y. M. (2012). Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Eng. Part A 18, 840-851. doi: 10.1089/ten.tea.2011.0362
115. Tanaka, T., Tohyama, S., Murata, M., Nomura, F., Kaneko, T., Chen, H., et al. (2009). In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem. Biophys. Res. Commun. 385, 497-502. doi: 10.1016/j.bbrc.2009.05.073
116. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147. doi: 10.1126/science.282.5391.1145
117. Till, J. E., and McCulloch, E. A. (1961). A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 14, 213-222. doi: 10.2307/3570892
118. Tulpule, A., Kelley, J. M., Lensch, M. W., McPherson, J., Park, I. H., Hartung, O., et al. (2013). Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell 12, 727-736. doi: 10.1016/j.stem.2013.04.002
119. Utikal, J., Maherali, N., Kulalert, W., and Hochedlinger, K. (2009). Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J. Cell Sci. 122, 3502-3510. doi: 10.1242/jcs.054783
120. Wang, X. M., Yik, W. Y., Zhang, P., Lu, W., Dranchak, P. K., Shibata, D., et al. (2012). The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis. Stem Cell Res. Ther. 3, 39. doi: 10.1186/scrt130
121. Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y. H., Li, H., Lau, F., et al. (2010). Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7, 618-630. doi: 10.1016/j.stem.2010.08.012
122. Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., and Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810-813. doi: 10.1038/385810a0
123. Wobus, A. M., and Loser, P. (2011). Present state and future perspectives of using pluripotent stem cells in toxicology research. Arch. Toxicol. 85, 79-117 doi: 10.1007/s00204-010-0641-6
124. Woltjen, K., Michael, I. P., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R., et al. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766-70. doi: 10.1038/nature07863
125. Xu, D., Alipio, Z., Fink, L. M., Adcock, D. M., Yang, J., and Ward, D. C. (2009). Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc. Natl. Acad. Sci. U.S.A. 106, 808-813. doi: 10.1073/pnas.0812090106
126. Yazawa, M., Hsueh, B., Jia, X., Pasca, A. M., Bernstein, J. A., Hallmayer, J., et al. (2011). Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471, 230-234. doi: 10.1038/nature09855
127. Ye, Z., Zhan, H., Mali, P., Dowey, S., Williams, D. M., Jang, Y. Y., et al. (2009). Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood 114, 5473-5480. doi: 10.1182/blood-2009-04-217406
128. Yokoo, N., Baba, S., Kaichi, S., Niwa, A., Mima, T., Doi, H., et al. (2009). The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells. Biochem. Biophys. Res. Commun. 387, 482-488. doi: 10.1016/j.bbrc.2009.07.052
129. Yoshida, T., Ozawa, Y., Suzuki, K., Yuki, K., Ohyama, M., Akamatsu, W., et al. (2014). The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Mol. Brain. 7:45. doi: 10.1186/1756-6606-7-45
130. Yoshida, Y., and Yamanaka, S. (2010). Recent stem cell advances: induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation 122, 80-87. doi: 10.1161/CIRCULATIONAHA.109.881433
131. Yoshioka, N., Gros, E., Li, H., Kumar, S., Deacon, D. C., and Maron, C. (2013). Efficient generation of human iPSCs by a synthetic self-replicative RNA. Cell Stem Cell 13, 246-254. doi: 10.1016/j.stem.2013.06.001
132. Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, I. I., et al. (2009). Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797-801. doi: 10.1126/science.1172482
133. Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920. doi: 10.1126/science.1151526
134. Yusa, K., Rad, R., Takeda, J., and Bradley, A. (2009). Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nat. Methods 6, 363-369. doi: 10.1038/nmeth.1323
135. Zhang, G., Shang, B., Yang, P., Cao, Z., Pan, Y., and Zhou, Q. (2012). Induced pluripotent stem cell consensus genes: implication for the risk of tumorigenesis and cancers in induced pluripotent stem cell therapy. Stem Cells Dev. 21, 955-964. doi: 10.1089/scd.2011.0649
136. Zhang, M., Yang, C., Liu, H., and Sun, Y. (2013). Induced pluripotent stem cells are sensitive to DNA damage. Genomics Proteomics Bioinformatics 11, 320-326. doi: 10.1016/j.gpb.2013.09.006
137. Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang, W., et al. (2008). Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3, 475-479. doi: 10.1016/j.stem.2008.10.002
138. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., and Melton, D. A. (2008). In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature 455, 627-632. doi: 10.1038/nature07314
139. Zhou, T., Benda, C., Dunzinger, S., Huang, Y., Ho, J. C., Yang, J., et al. (2012). Generation of human induced pluripotent stem cells from urine samples. Nat. Protoc. 7, 2080-2089. doi: 10.1038/nprot.2012.115