Preclinical studies for induced pluripotent stem cell-based therapeutics

Journal of Biological Chemistry

Volumn 289, Issue 8, 2014, Pages 4585-4593

  Harding, John ^a   Mirochnitchenko, Oleg ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; CELL PROLIFERATION; STEM CELLS;

CELL-BASED THERAPY; CELLULAR DIFFERENTIATION; GENETIC INSTABILITY; INDUCED PLURIPOTENT STEM CELLS; METABOLIC CONDITIONS; PRECLINICAL STUDIES; THERAPEUTIC APPLICATION; TRANSPLANTED CELLS;

DISEASE CONTROL;

CARCINOGENICITY; CARDIOMYOPATHY; CELL DIFFERENTIATION; CELL FUNCTION; CELL POPULATION; CELL SURVIVAL; CEREBROVASCULAR ACCIDENT; ENGRAFTMENT; GENOMIC INSTABILITY; HEART INFARCTION; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; LIVER CIRRHOSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OPTIC CHIASM; PARKINSON DISEASE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; QUALITY CONTROL; RETINITIS PIGMENTOSA; REVIEW; SPINAL CORD INJURY; STEM CELL TRANSPLANTATION;

ANIMAL MODELS; DIFFERENTIATION; INDUCED PLURIPOTENT STEM CELL (IPSC); REGENERATIVE MEDICINE; STEM CELLS;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; INDUCED PLURIPOTENT STEM CELLS; STEM CELL TRANSPLANTATION;

EID: 84894491411     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R113.463737     Document Type: Review

References (99)

1. Yamanaka, S. (2012) Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10, 678-684
2. Takahashi, K., and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676
3. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872
4. Liu, H., Zhu, F., Yong, J., Zhang, P., Hou, P., Li, H., Jiang, W., Cai, J., Liu, M., Cui, K., Qu, X., Xiang, T., Lu, D., Chi, X., Gao, G., Ji, W., Ding, M., and Deng, H. (2008) Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell 3, 587-590
5. Liao, J., Cui, C., Chen, S., Ren, J., Chen, J., Gao, Y., Li, H., Jia, N., Cheng, L., Xiao, H., and Xiao, L. (2009) Generation of induced pluripotent stem cell lines from adult rat cells. Cell Stem Cell 4, 11-15
6. Honda, A., Hirose, M., Hatori, M., Matoba, S., Miyoshi, H., Inoue, K., and Ogura, A. (2010) Generation of induced pluripotent stem cells in rabbits: potential experimental models for human regenerative medicine. J. Biol. Chem. 285, 31362-31369
7. Lee, A. S., Xu, D., Plews, J. R., Nguyen, P. K., Nag, D., Lyons, J. K., Han, L., Hu, S., Lan, F., Liu, J., Huang, M., Narsinh, K. H., Long, C. T., de Almeida, P. E., Levi, B., Kooreman, N., Bangs, C., Pacharinsak, C., Ikeno, F., Yeung, A. C., Gambhir, S. S., Robbins, R. C., Longaker, M. T., and Wu, J. C. (2011) Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells. J. Biol. Chem. 286, 32697-32704
8. Wu, Y., Mishra, A., Qiu, Z., Farnsworth, S., Tardif, S. D., and Hornsby, P. J. (2012) Nonhuman primate induced pluripotent stem cells in regenerative medicine. Stem Cells Int. 2012, 767195
9. Ezashi, T., Telugu, B. P., and Roberts, R. M. (2012) Induced pluripotent stem cells from pigs and other ungulate species: an alternative to embryonic stem cells? Reprod. Domest. Anim. 47, Suppl. 4, 92-97
10. Shultz, L. D., Brehm, M. A., Garcia-Martinez, J. V., and Greiner, D. L. (2012) Humanized mice for immune system investigation: progress, promise and challenges. Nat. Rev. Immunol. 12, 786-798
11. Suzuki, S., Iwamoto, M., Saito, Y., Fuchimoto, D., Sembon, S., Suzuki, M., Mikawa, S., Hashimoto, M., Aoki, Y., Najima, Y., Takagi, S., Suzuki, N., Suzuki, E., Kubo, M., Mimuro, J., Kashiwakura, Y., Madoiwa, S., Sakata, Y., Perry, A. C., Ishikawa, F., and Onishi, A. (2012) Il2rg gene-targeted severe combined immunodeficiency pigs. Cell Stem Cell 10, 753-758
12. de Almeida, P. E., Ransohoff, J. D., Nahid, A., and Wu, J. C. (2013) Immunogenicity of pluripotent stem cells and their derivatives. Circ. Res. 112, 549-561
13. Zhao, T., Zhang, Z. N., Rong, Z., and Xu, Y. (2011) Immunogenicity of induced pluripotent stem cells. Nature 474, 212-215
14. 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
15. Araki, R., Uda, M., Hoki, Y., Sunayama, M., Nakamura, M., Ando, S., Sugiura, M., Ideno, H., Shimada, A., Nifuji, A., and Abe, M. (2013) Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 494, 100-104
16. Hannan, N. R., Segeritz, C. P., Touboul, T., and Vallier, L. (2013) Production of hepatocyte-like cells from human pluripotent stem cells. Nat. Protoc. 8, 430-437
17. Liu, H., Kim, Y., Sharkis, S., Marchionni, L., and Jang, Y. Y. (2011) In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci. Transl. Med. 3, 82ra39
18. Chen, Y. F., Tseng, C. Y., Wang, H. W., Kuo, H. C., Yang, V. W., and Lee, O. K. (2012) Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Hepatology 55, 1193-1203
19. Yusa, K., Rashid, S. T., Strick-Marchand, H., Varela, I., Liu, P. Q., Paschon, D. E., Miranda, E., Ordóñez, A., Hannan, N. R., Rouhani, F. J., Darche, S., Alexander, G., Marciniak, S. J., Fusaki, N., Hasegawa, M., Holmes, M. C., Di Santo, J. P., Lomas, D. A., Bradley, A., and Vallier, L. (2011) Targeted gene correction of 1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478, 391-394
20. Emborg, M. E., Liu, Y., Xi, J., Zhang, X., Yin, Y., Lu, J., Joers, V., Swanson, C., Holden, J. E., and Zhang, S. C. (2013) Induced pluripotent stem cellderived neural cells survive and mature in the nonhuman primate brain. Cell Rep. 3, 646-650
21. Rhee, Y. H., Ko, J. Y., Chang, M. Y., Yi, S. H., Kim, D., Kim, C. H., Shim, J. W., Jo, A. Y., Kim, B. W., Lee, H., Lee, S. H., Suh, W., Park, C. H., Koh, H. C., Lee, Y. S., Lanza, R., Kim, K. S., and Lee, S. H. (2011) Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J. Clin. Invest. 121, 2326-2335
22. Pouya, A., Satarian, L., Kiani, S., Javan, M., and Baharvand, H. (2011) Human induced pluripotent stem cell differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination. PLoS ONE 6, e27925
23. Nori, S., Okada, Y., Yasuda, A., Tsuji, O., Takahashi, Y., Kobayashi, Y., Fujiyoshi, K., Koike, M., Uchiyama, Y., Ikeda, E., Toyama, Y., Yamanaka, S., Nakamura, M., and Okano, H. (2011) Grafted 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
24. Kobayashi, Y., Okada, Y., Itakura, G., Iwai, H., Nishimura, S., Yasuda, A., Nori, S., Hikishima, K., Konomi, T., Fujiyoshi, K., Tsuji, O., Toyama, Y., Yamanaka, S., Nakamura, M., and Okano, H. (2012) Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity. PLoS ONE 7, e52787
25. Kawai, H., Yamashita, T., Ohta, Y., Deguchi, K., Nagotani, S., Zhang, X., Ikeda, Y., Matsuura, T., and Abe, K. (2010) Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain. J. Cereb. Blood Flow Metab. 30, 1487-1493
26. Jensen, M. B., Yan, H., Krishnaney-Davison, R., Al Sawaf, A., and Zhang, S. C. (2013) Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model. J. Stroke Cerebrovasc. Dis. 22, 304-308
27. Oki, K., Tatarishvili, J., Wood, J., Koch, P., Wattananit, S., Mine, Y., Monni, E., Tornero, D., Ahlenius, H., Ladewig, J., Brüstle, O., Lindvall, O., and Kokaia, Z. (2012) Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain. Stem Cells 30, 1120-1133
28. Gomi, M., Takagi, Y., Morizane, A., Doi, D., Nishimura, M., Miyamoto, S., and Takahashi, J. (2012) Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors. Brain Res. 1459, 52-60
29. Tucker, B. A., Park, I. H., Qi, S. D., Klassen, H. J., Jiang, C., Yao, J., Redenti, S., Daley, G. Q., and Young, M. J. (2011) Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice. PLoS ONE 6, e18992
30. Zhou, L., Wang, W., Liu, Y., Fernandez de Castro, J., Ezashi, T., Telugu, B. P., Roberts, R. M., Kaplan, H. J., and Dean, D. C. (2011) Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells 29, 972-980
31. Li, Y., Tsai, Y. T., Hsu, C. W., Erol, D., Yang, J., Wu, W. H., Davis, R. J., Egli, D., and Tsang, S. H. (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
32. Mauritz, C., Schwanke, K., Reppel, M., Neef, S., Katsirntaki, K., Maier, L. S., Nguemo, F., Menke, S., Haustein, M., Hescheler, J., Hasenfuss, G., and Martin, U. (2008) Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation 118, 507-517
33. Martinez-Fernandez, A., Nelson, T. J., Yamada, S., Reyes, S., Alekseev, A. E., Perez-Terzic, C., Ikeda, Y., and Terzic, A. (2009) iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circ. Res. 105, 648-656
34. Zwi, L., Caspi, O., Arbel, G., Huber, I., Gepstein, A., Park, I. H., and Gepstein, L. (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120, 1513-1523
35. Zhang, J., Wilson, G. F., Soerens, A. G., Koonce, C. H., Yu, J., Palecek, S. P., Thomson, J. A., and Kamp, T. J. (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ. Res. 104, e30-e41
36. Kattman, S. J., Witty, A. D., Gagliardi, M., Dubois, N. C., Niapour, M., Hotta, A., Ellis, J., and Keller, G. (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8, 228-240
37. Carpenter, L., Carr, C., Yang, C. T., Stuckey, D. J., Clarke, K., and Watt, S. M. (2012) Efficient differentiation of human induced pluripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat. Stem Cells Dev. 21, 977-986
38. Gu, M., Nguyen, P. K., Lee, A. S., Xu, D., Hu, S., Plews, J. R., Han, L., Huber, B. C., Lee, W. H., Gong, Y., de Almeida, P. E., Lyons, J., Ikeno, F., Pacharinsak, C., Connolly, A. J., Gambhir, S. S., Robbins, R. C., Longaker, M. T., and Wu, J. C. (2012) Microfluidic single-cell analysis shows that porcine induced pluripotent stem cell-derived endothelial cells improve myocardial function by paracrine activation. Circ. Res. 111, 882-893
39. Templin, C., Zweigerdt, R., Schwanke, K., Olmer, R., Ghadri, J. R., Emmert, M. Y., Müller, E., Küest, S. M., Cohrs, S., Schibli, R., Kronen, P., Hilbe, M., Reinisch, A., Strunk, D., Haverich, A., Hoerstrup, S., Lüscher, T. F., Kaufmann, P. A., Landmesser, U., and Martin, U. (2012) Transplantation and tracking of human-induced pluripotent stem cells in a pig model of myocardial infarction: assessment of cell survival, engraftment, and distribution by hybrid single photon emission computed tomography/ computed tomography of sodium iodide symporter transgene expression. Circulation 126, 430-439
40. Kawamura, M., Miyagawa, S., Miki, K., Saito, A., Fukushima, S., Higuchi, T., Kawamura, T., Kuratani, T., Daimon, T., Shimizu, T., Okano, T., and Sawa, Y. (2012) Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126, S29-S37
41. Alipio, Z., Liao, W., Roemer, E. J., Waner, M., Fink, L. M., Ward, D. C., and Ma, Y. (2010) Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreaticlike cells. Proc. Natl. Acad. Sci. U.S.A. 107, 13426-13431
42. Zhu, F. F., Zhang, P. B., Zhang, D. H., Sui, X., Yin, M., Xiang, T. T., Shi, Y., Ding, M. X., and Deng, H. (2011) Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells. Diabetologia 54, 2325-2336
43. Thatava, T., Nelson, T. J., Edukulla, R., Sakuma, T., Ohmine, S., Tonne, J. M., Yamada, S., Kudva, Y., Terzic, A., and Ikeda, Y. (2011) Indolactam V/GLP-1-mediated differentiation of human iPS cells into glucose-responsive insulin-secreting progeny. Gene Ther. 18, 283-293
44. Bar-Nur, O., Russ, H. A., Efrat, S., and Benvenisty, N. (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet cells. Cell Stem Cell 9, 17-23
45. Jeon, K., Lim, H., Kim, J. H., Thuan, N. V., Park, S. H., Lim, Y. M., Choi, H. Y., Lee, E. R., Kim, J. H., Lee, M. S., and Cho, S. G. (2012) Differentiation and transplantation of functional pancreatic cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model. Stem Cells Dev. 21, 2642-2655
46. Gu, E., Chen, W. Y., Gu, J., Burridge, P., and Wu, J. C. (2012) Molecular imaging of stem cells: tracking survival, biodistribution, tumorigenicity, and immunogenicity. Theranostics 2, 335-345
47. Ruggiero, A., Thorek, D. L., Guenoun, J., Krestin, G. P., and Bernsen, M. R. (2012) Cell tracking in cardiac repair: what to image and how to image. Eur. Radiol. 22, 189-204
48. Cai, W., Zhang, Y., and Kamp, T. J. (2011) Imaging of induced pluripotent stem cells: from cellular reprogramming to transplantation. Am. J. Nucl. Med. Mol. Imaging 1, 18-28
49. Sohn, Y. D., Han, J. W., and Yoon, Y. S. (2012) Generation of induced pluripotent stem cells from somatic cells. Prog. Mol. Biol. Transl. Sci. 111, 1-26
50. Maekawa, M., Yamaguchi, K., Nakamura, T., Shibukawa, R., Kodanaka, I., Ichisaka, T., Kawamura, Y., Mochizuki, H., Goshima, N., and Yamanaka, S. (2011) Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474, 225-229
51. Zhang, Y., Yao, L., Yu, X., Ou, J., Hui, N., and Liu, S. (2012) A poor imitation of a natural process: a call to reconsider the iPSC engineering technique. Cell Cycle 11, 4536-4544
52. Hussein, S. M., and Nagy, A. A. (2012) Progress made in the reprogramming field: new factors, new strategies and a new outlook. Curr. Opin. Genet. Dev. 22, 435-443
53. Li, M., Sancho-Martinez, I., and Izpisua Belmonte, J. C. (2011) Cell fate conversion by mRNA. Stem Cell Res. Ther. 2, 5
54. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., and Hochedlinger, K. (2008) Induced pluripotent stem cells generated without viral integration. Science 322, 945-949
55. Kim, D., Kim, C. H., Moon, J. I., Chung, Y. G., Chang, M. Y., Han, B. S., Ko, S., Yang, E., Cha, K. Y., Lanza, R., and Kim, K. S. (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4, 472-476
56. Lund, R. J., Närvä, E., and Lahesmaa, R. (2012) Genetic and epigenetic stability of human pluripotent stem cells. Nat. Rev. Genet. 13, 732-744
57. Kim, K., Zhao, R., Doi, A., Ng, K., Unternaehrer, J., Cahan, P., Huo, H., Loh, Y. H., Aryee, M. J., Lensch, M. W., Li, H., Collins, J. J., Feinberg, A. P., and Daley, G. Q. (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat. Biotechnol. 29, 1117-1119
58. Ruiz, S., Diep, D., Gore, A., Panopoulos, A. D., Montserrat, N., Plongthongkum, N., Kumar, S., Fung, H. L., Giorgetti, A., Bilic, J., Batchelder, E. M., Zaehres, H., Kan, N. G., Schöler, H. R., Mercola, M., Zhang, K., and Izpisua Belmonte, J. C. (2012) Identification of a specific reprogrammingassociated epigenetic signature in human induced pluripotent stem cells. Proc. Natl. Acad. Sci. U.S.A. 109, 16196-16201
59. Nazor, K. L., Altun, G., Lynch, C., Tran, H., Harness, J. V., Slavin, I., Garitaonandia, I., Müller, F. J., Wang, Y. C., Boscolo, F. S., Fakunle, E., Dumevska, B., Lee, S., Park, H. S., Olee, T., D'Lima, D. D., Semechkin, R., Parast, M. M., Galat, V., Laslett, A. L., Schmidt, U., Keirstead, H. S., Loring, J. F., and Laurent, L. C. (2012) Recurrent variations inDNAmethylation in human pluripotent stem cells and their differentiated derivatives. Cell Stem Cell 10, 620-634
60. van der Bogt, K. E., Sheikh, A. Y., Schrepfer, S., Hoyt, G., Cao, F., Ransohoff, K. J., Swijnenburg, R. J., Pearl, J., Lee, A., Fischbein, M., Contag, C. H., Robbins, R. C., and Wu, J. C. (2008) Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation 118, S121-S129
61. Wu, Y. M., Joseph, B., Berishvili, E., Kumaran, V., and Gupta, S. (2008) Hepatocyte transplantation and drug-induced perturbations in liver cell compartments. Hepatology 47, 279-287
62. Soto-Gutierrez, A., Yagi, H., Uygun, B. E., Navarro-Alvarez, N., Uygun, K., Kobayashi, N., Yang, Y. G., and Yarmush, M. L. (2010) Cell delivery: from cell transplantation to organ engineering. Cell Transplant. 19, 655-665
63. Hibino, N., Duncan, D. R., Nalbandian, A., Yi, T., Qyang, Y., Shinoka, T., and Breuer, C. K. (2012) Evaluation of the use of an induced puripotent stem cell sheet for the construction of tissue-engineered vascular grafts. J. Thorac. Cardiovasc. Surg. 143, 696-703
64. Yang, J. J., Liu, J. F., Kurokawa, T., Kitada, K., and Gong, J. P. (2012) Hydrogels as feeder-free scaffolds for long-term self-renewal of mouse induced pluripotent stem cells. J. Tissue Eng. Regen. Med. 10.1002/ term.1640
65. Taapken, S. M., Nisler, B. S., Newton, M. A., Sampsell-Barron, T. L., Leonhard, K. A., McIntire, E. M., and Montgomery, K. D. (2011) Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat. Biotechnol. 29, 313-314
66. Chen, Q., Shi, X., Rudolph, C., Yu, Y., Zhang, D., Zhao, X., Mai, S., Wang, G., Schlegelberger, B., and Shi, Q. (2011) Recurrent trisomy and Robertsonian translocation of chromosome 14 in murine iPS cell lines. Chromosome Res. 19, 857-868
67. Ronen, D., and Benvenisty, N. (2012) Genomic stability in reprogramming. Curr. Opin. Genet. Dev. 22, 444-449
68. Hong, S. G., Dunbar, C. E., and Winkler, T. (2013) Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells. Mol. Ther. 21, 272-281
69. Gore, A., Li, Z., Fung, H. L., Young, J. E., Agarwal, S., Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M. A., Kiskinis, E., Lee, J. H., Loh, Y. H., Manos, P. D., Montserrat, N., Panopoulos, A. D., Ruiz, S., Wilbert, M. L., Yu, J., Kirkness, E. F., Izpisua Belmonte, J. C., Rossi, D. J., Thomson, J. A., Eggan, K., Daley, G. Q., Goldstein, L. S., and Zhang, K. (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471, 63-67
70. Ji, J., Ng, S. H., Sharma, V., Neculai, D., Hussein, S., Sam, M., Trinh, Q., Church, G. M., McPherson, J. D., Nagy, A., and Batada, N. N. (2012) Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells 30, 435-440
71. Quinlan, A. R., Boland, M. J., Leibowitz, M. L., Shumilina, S., Pehrson, S. M., Baldwin, K. K., and Hall, I. M. (2011) Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Cell Stem Cell 9, 366-373
72. Martins-Taylor, K., Nisler, B. S., Taapken, S. M., Compton, T., Crandall, L., Montgomery, K. D., Lalande, M., and Xu, R. H. (2011) Recurrent copy number variations in human induced pluripotent stem cells. Nat. Biotechnol. 29, 488-491
73. Ben-David, U., and Benvenisty, N. (2012) High prevalence of evolutionarily conserved and species-specific genomic aberrations in mouse pluripotent stem cells. Stem Cells 30, 612-622
74. Koh, S., Thomas, R., Tsai, S., Bischoff, S., Lim, J. H., Breen, M., Olby, N. J., and Piedrahita, J. A. (2013) Growth requirements and chromosomal instability of induced pluripotent stem cells generated from adult canine fibroblasts. Stem Cells Dev. 22, 951-963
75. Nishino, K., Toyoda, M., Yamazaki-Inoue, M., Fukawatase, Y., Chikazawa, E., Sakaguchi, H., Akutsu, H., and Umezawa, A. (2011) DNA methylation dynamics in human induced pluripotent stem cells over time. PLoS Genet. 7, e1002085
76. Lister, R., Pelizzola, M., Kida, Y. S., Hawkins, R. D., Nery, J. R., Hon, G., Antosiewicz-Bourget, J., O'Malley, R., Castanon, R., Klugman, S., Downes, M., Yu, R., Stewart, R., Ren, B., Thomson, J. A., Evans, R. M., and Ecker, J. R. (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68-73
77. Ohi, Y., Qin, H., Hong, C., Blouin, L., Polo, J. M., Guo, T., Qi, Z., Downey, S. L., Manos, P. D., Rossi, D. J., Yu, J., Hebrok, M., Hochedlinger, K., Costello, J. F., Song, J. S., and Ramalho-Santos, M. (2011) IncompleteDNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat. Cell Biol. 13, 541-549
78. Semi, K., Matsuda, Y., Ohnishi, K., and Yamada, Y. (2013) Cellular reprogramming and cancer development. Int. J. Cancer 132, 1240-1248
79. Nelson, T. J., Martinez-Fernandez, A., Yamada, S., Perez-Terzic, C., Ikeda, Y., and Terzic, A. (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120, 408-416
80. Yamashita, T., Kawai, H., Tian, F., Ohta, Y., and Abe, K. (2011) Tumorigenic development of induced pluripotent stem cells in ischemic mouse brain. Cell Transplant. 20, 883-891
81. Miura, K., Okada, Y., Aoi, T., Okada, A., Takahashi, K., Okita, K., Nakagawa, M., Koyanagi, M., Tanabe, K., Ohnuki, M., Ogawa, D., Ikeda, E., Okano, H., and Yamanaka, S. (2009) Variation in the safety of induced pluripotent stem cell lines. Nat. Biotechnol. 27, 743-745
82. Zhang, Y., Wang, D., Chen, M., Yang, B., Zhang, F., and Cao, K. (2011) Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart. PLoS ONE 6, e19012
83. Tong, M., Lv, Z., Liu, L., Zhu, H., Zheng, Q. Y., Zhao, X. Y., Li, W., Wu, Y. B., Zhang, H. J., Wu, H. J., Li, Z. K., Zeng, F., Wang, L., Wang, X. J., Sha, J. H., and Zhou, Q. (2011) Mice generated from tetraploid complementation competent iPS cells show similar developmental features as those from ES cells but are prone to tumorigenesis. Cell Res. 21, 1634-1637
84. Ghosh, Z., Huang, M., Hu, S., Wilson, K. D., Dey, D., and Wu, J. C. (2011) Dissecting the oncogenic and tumorigenic potential of differentiated human induced pluripotent stem cells and human embryonic stem cells. Cancer Res. 71, 5030-5039
85. 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
86. Kuroda, T., Yasuda, S., Kusakawa, S., Hirata, N., Kanda, Y., Suzuki, K., Takahashi, M., Nishikawa, S., Kawamata, S., and Sato, Y. (2012) Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells. PLoS ONE 7, e37342
87. Tang, C., Lee, A. S., Volkmer, J. P., Sahoo, D., Nag, D., Mosley, A. R., Inlay, M. A., Ardehali, R., Chavez, S. L., Pera, R. R., Behr, B., Wu, J. C., Weissman, I. L., and Drukker, M. (2011) An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat. Biotechnol. 29, 829-834
88. Menendez, S., Camus, S., Herreria, A., Paramonov, I., Morera, L. B., Collado, M., Pekarik, V., Maceda, I., Edel, M., Consiglio, A., Sanchez, A., Li, H., Serrano, M., and Belmonte, J. C. (2012) Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency. Aging Cell 11, 41-50
89. Joven, J., Menéndez, J. A., Fernandez-Sender, L., Espinel, E., Rull, A., Beltra ́n-Debón, R., Rodríguez-Gallego, E., Riera-Borrull, M., Pedro-Botet, J., Alonso-Villaverde, C., Camps, J., and Aragonès, G. (2013) Metformin: a cheap and well-tolerated drug that provides benefits for viral infections. HIV Med. 14, 233-240
90. Ben-David, U., Gan, Q. F., Golan-Lev, T., Arora, P., Yanuka, O., Oren, Y. S., Leikin-Frenkel, A., Graf, M., Garippa, R., Boehringer, M., Gromo, G., and Benvenisty, N. (2013) Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen. Cell Stem Cell 12, 167-179
91. Kuroda, T., Yasuda, S., and Sato, Y. (2013) Tumorigenicity studies for human pluripotent stem cell-derived products. Biol. Pharm. Bull. 36, 189-192
92. Mashimo, T., Takizawa, A., Kobayashi, J., Kunihiro, Y., Yoshimi, K., Ishida, S., Tanabe, K., Yanagi, A., Tachibana, A., Hirose, J., Yomoda, J., Morimoto, S., Kuramoto, T., Voigt, B., Watanabe, T., Hiai, H., Tateno, C., Komatsu, K., and Serikawa, T. (2012) Generation and characterization of severe combined immunodeficiency rats. Cell Rep. 2, 685-694
93. Varela, C., Denis, J. A., Polentes, J., Feyeux, M., Aubert, S., Champon, B., Piétu, G., Peschanski, M., and Lefort, N. (2012) Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells. J. Clin. Invest. 122, 569-574
94. Zhong, B., Watts, K. L., Gori, J. L., Wohlfahrt, M. E., Enssle, J., Adair, J. E., and Kiem, H. P. (2011) Safeguarding nonhuman primate iPS cells with suicide genes. Mol. Ther. 19, 1667-1675
95. Chen, F., Cai, B., Gao, Y., Yuan, X., Cheng, F., Wang, T., Jiang, M., Zhou, Y., Lahn, B. T., Li, W., and Xiang, A. P. (2013) Suicide gene-mediated ablation of tumor-initiating mouse pluripotent stem cells. Biomaterials 34, 1701-1711
96. Cheng, F., Ke, Q., Chen, F., Cai, B., Gao, Y., Ye, C., Wang, D., Zhang, L., Lahn, B. T., Li, W., and Xiang, A. P. (2012) Protecting against wayward human induced pluripotent stem cells with a suicide gene. Biomaterials 33, 3195-3204
97. Knoepfler, P. S. (2012) Key anticipated regulatory issues for clinical use of human induced pluripotent stem cells. Regen. Med. 7, 713-720
98. Morris, S. A., and Daley, G. Q. (2013) A blueprint for engineering cell fate: current technologies to reprogram cell identity. Cell Res. 23, 33-48
99. Sancho-Martinez, I., Baek, S. H., and Izpisua Belmonte, J. C. (2012) Lineage conversion methodologies meet the reprogramming toolbox. Nat. Cell Biol. 14, 892-899