Journal of Zhejiang University SCIENCE B

, Volume 14, Issue 12, pp 1059–1069 | Cite as

Induced pluripotent stem cells: origins, applications, and future perspectives



Embryonic stem (ES) cells are widely used for different purposes, including gene targeting, cell therapy, tissue repair, organ regeneration, and so on. However, studies and applications of ES cells are hindered by ethical issues regarding cell sources. To circumvent ethical disputes, great efforts have been taken to generate ES cell-like cells, which are not derived from the inner cell mass of blastocyst-stage embryos. In 2006, Yamanaka et al. first reprogrammed mouse embryonic fibroblasts into ES cell-like cells called induced pluripotent stem (iPS) cells. About one year later, Yamanaka et al. and Thomson et al. independently reprogrammed human somatic cells into iPS cells. Since the first generation of iPS cells, they have now been derived from quite a few different kinds of cell types. In particular, the use of peripheral blood facilitates research on iPS cells because of safety, easy availability, and plenty of cell sources. Now iPS cells have been used for cell therapy, disease modeling, and drug discovery. In this review, we describe the generations, applications, potential issues, and future perspectives of iPS cells.

Key words

Induced pluripotent stem cells Origin Peripheral blood cells Application Potential issues 

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  1. Aasen, T., Raya, A., Barrero, M.J., Garreta, E., Consiglio, A., Gonzalez, F., Vassena, R., Bilić, J., Pekarik, V., Tiscornia, G., et al., 2008. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat. Biotechnol., 26(11):1276–1284. [doi:10.1038/nbt.1503]PubMedCrossRefGoogle Scholar
  2. Anokye-Danso, F., Trivedi, C.M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P.J., Epstein, J.A., et al., 2011. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell, 8(4):376–388. [doi:10.1016/j.stem.2011.03.001]PubMedCrossRefGoogle Scholar
  3. Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T., Yamanaka, S., 2008. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321(5889):699–702. [doi:10.1126/science.1154884]PubMedCrossRefGoogle Scholar
  4. Aoki, T., Ohnishi, H., Oda, Y., Tadokoro, M., Sasao, M., Kato, H., Hattori, K., Ohgushi, H., 2010. Generation of induced pluripotent stem cells from human adipose-derived stem cells without c-Myc. Tissue Eng. Part A, 16(7):2197–2206. [doi:10.1089/ten.tea.2009.0747]PubMedCrossRefGoogle Scholar
  5. Carvajal-Vergara, X., Sevilla, A., D’Souza, S.L., Ang, Y.S., Schaniel, C., Lee, D.F., Yang, L., Kaplan, A.D., Adler, E.D., Rozov, R., et al., 2010. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature, 465(7299):808–812. [doi:10.1038/nature09005]PubMedCrossRefGoogle Scholar
  6. Chang, M.Y., Kim, D., Kim, C.H., Kang, H.C., Yang, E., Moon, J.I., Ko, S., Park, J., Park, K.S., Lee, K.A., et al., 2010. Direct reprogramming of rat neural precursors cells and fibroblasts into pluripotent stem cells. PLoS ONE, 5(3):e9838. [doi:10.1371/journal.pone.0009838]PubMedCrossRefGoogle Scholar
  7. Chesné, P., Adenot, P.G., Viglietta, C., Baratte, M., Boulanger, L., Renard, J.P., 2002. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nat. Biotechnol., 20(4):366–369. [doi:10.1038/nbt0402-366]PubMedCrossRefGoogle Scholar
  8. Cho, H.J., Lee, C.S., Kwon, Y.W., Paek, J.S., Lee, S.H., Hur, J., Lee, E.J., Roh, T.Y., Chu, I.S., Leem, S.H., et al., 2010. Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation. Blood, 116(3):386–395. [doi:10.1182/blood-2010-02-269589]PubMedCrossRefGoogle Scholar
  9. Chou, B.K., Mali, P., Huang, X., Ye, Z., Dowey, S.N., Resar, L.M., Zou, C., Zhang, Y.A., Tong, J., Cheng, L., 2011. Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res., 21(3):518–529. [doi:10.1038/cr.2011.12]PubMedCrossRefGoogle Scholar
  10. Desponts, C., Ding, S., 2010. Using small molecules to improve generation of induced pluripotent stem cells from somatic cells. Methods Mol. Biol., 636:207–218. [doi:10. 1007/978-1-60761-691-7_13]PubMedCrossRefGoogle Scholar
  11. Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., et al., 2008. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893): 1218–1221. [doi:10.1126/science.1158799]PubMedCrossRefGoogle Scholar
  12. Easley, C.A.4th, Phillips, B.T., McGuire, M.M., Barringer, J.M., Valli, H., Hermann, B.P., Simerly, C.R., Rajkovic, A., Miki, T., Orwig, K.E., et al., 2012. Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells. Cell Rep., 2(3):440–446. [doi:10.1016/j.celrep.2012.07.015]PubMedCrossRefGoogle Scholar
  13. Ebert, A.D., Yu, J.Y., Rose, F.F., Mattis, V.B., Lorson, C.L., Thomson, J.A., Svendsen, C.N., 2009. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457(7227):277–280. [doi:10.1038/nature07677]PubMedCrossRefGoogle Scholar
  14. Ebihara, Y., Ma, F., Tsuji, K., 2012. Generation of red blood cells from human embryonic/induced pluripotent stem cells for blood transfusion. Int. J. Hematol., 95(6): 610–616. [doi:10.1007/s12185-012-1107-9]PubMedCrossRefGoogle Scholar
  15. Eminli, S., Foudi, A., Stadtfeld, M., Maherali, N., Ahfeldt, T., Mostoslavsky, G., Hock, H., Hochedlinger, K., 2009. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat. Genet., 41(9):968–976. [doi:10.1038/ng.428]PubMedCrossRefGoogle Scholar
  16. Evans, M.J., Kaufman, M.H., 1981. Establishment in culture of pluripotent cells from mouse embryos. Nature, 292(5819):154–156. [doi:10.1038/292154a0]PubMedCrossRefGoogle Scholar
  17. Feng, B., Jiang, J., Kraus, P., Ng, J.H., Heng, J.C., Chan, Y.S., Yaw, L.P., Zhang, W., Loh, Y.H., Han, J., et al., 2009. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat. Cell Biol., 11(2):197–203. [doi:10.1038/ncb1827]PubMedCrossRefGoogle Scholar
  18. Fusaki, N., Ban, H., Nishiyama, A., Saeki, K., 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(8):348–362. [doi:10.2183/pjab.85.348]PubMedCrossRefGoogle Scholar
  19. Giorgetti, A., Montserrat, N., Aasen, T., Gonzalez, F., Rodríguez-Pizà, I., Vassena, R., Raya, A., Boué, S., Barrero, M.J., Corbella, B.A., et al., 2009. Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell, 5(4):353–357. [doi:10.1016/j.stem.2009.09.008]PubMedCrossRefGoogle Scholar
  20. Gore, A., Li, A., Fung, H.L., Young, J.E., Agarwal, S., Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M.A., Kiskinis, E., et al., 2011. Somatic coding mutations in human induced pluripotent stem cells. Nature, 471(7336):63–67. [doi:10.1038/nature09805]PubMedCrossRefGoogle Scholar
  21. Gurdon, J.B., 1962. The development capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Embryol. Exp. Morphol., 10(4):622–640.Google Scholar
  22. Haase, A., Olmer, R., Schwanke, K., Wunderlich, S., Merkert, S., Hess, C., Zweigerdt, R., Gruh, I., Meyer, J., Wagner, S., et al., 2009. Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell, 5(4): 434–441. [doi:10.1016/j.stem.2009.08.021]PubMedCrossRefGoogle Scholar
  23. Hanna, J., Wernig, M., Markoulaki, S., Sun, C.W., Meissner, A., Cassady, J.P., Beard, C., Brambrink, T., Wu, L.C., Townes, T.M., et al., 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858):1920–1923. [doi:10.1126/science.1152092]PubMedCrossRefGoogle Scholar
  24. Hanna, J., Markoulaki, S., Schorderet, P., Carey, B.W., Beard, C., Wernig, M., Creyghton, M.P., Steine, E.J., Cassady, J.P., Foreman, R., et al., 2008. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133(2):250–264. [doi:10.1016/j.cell.2008.03.028]PubMedCrossRefGoogle Scholar
  25. Heng, J.C., Feng, B., Han, J., Jiang, J., Kraus, P., Ng, J.H., Orlov, Y.L., Huss, M., Yang, L., Lufkin, T., et al., 2010. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell, 6(2):167–174. [doi:10.1016/j.stem.2009.12.009]PubMedCrossRefGoogle Scholar
  26. Honda, A., Hirose, M., Hatori, M., Matoba, S., Miyoshi, H., Inoue, K., Ogura, A., 2010. Generation of induced pluripotent stem cells in rabbits: potential experimental models for human regenerative medicine. J. Biol. Chem., 285(41):31362–31369. [doi:10.1074/jbc.M110.150540]PubMedCrossRefGoogle Scholar
  27. Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., Yamanaka, S., 2009. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature, 460(7259):1132–1135. [doi:10.1038/nature08235]PubMedCrossRefGoogle Scholar
  28. Hotta, A., Cheung, A.Y., Farra, N., Vijayaragavan, K., Séguin, C.A., Draper, J.S., Pasceri, P., Maksakova, I.A., Mager, D.L., Rossant, J., et al., 2009. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat. Methods, 6(5):370–376. [doi:10.1038/nmeth.1325]PubMedCrossRefGoogle Scholar
  29. Hou, P.P., Li, Y.Q., Zhang, X., Liu, C., Guan, J.Y., Li, H.G., Zhao, T., Ye, J.Q., Zhao, Y., Deng, H.K., 2013. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science, 341(6146):651–654. [doi:10.1126/science.1239278]PubMedCrossRefGoogle Scholar
  30. Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., Muhlestein, W., Melton, D.A., 2008. Melton induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol., 26(11):1269–1275. [doi:10.1038/nbt.1502]PubMedCrossRefGoogle Scholar
  31. Kaji, K., Norrby, K., Paca, A., Mileikovsky, M., Mohseni, P., Woltjen, K., 2009. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 458(7239):771–775. [doi:10.1038/nature07864]PubMedCrossRefGoogle Scholar
  32. Kang, L., Wang, J., Zhang, Y., Kou, Z., Gao, S., 2009. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell, 5(2): 135–138. [doi:10.1016/j.stem.2009.07.001]PubMedCrossRefGoogle Scholar
  33. Kim, D., Kim, C.H., Moon, J.I., Chung, Y.G., Chang, M.Y., Han, B.S., Yang, E., Cha, K.Y., Lanza, R., Kim, K.S., 2009. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 4(6):472–476. [doi:10.1016/j.stem.2009.05.005]PubMedCrossRefGoogle Scholar
  34. Kim, J.B., Zaehres, H., Wu, G., Gentile, L., Ko, K., Sebastiano, V., Araúzo-Bravo, M.J., Ruau, D., Han, D.W., Zenke, M., et al., 2008. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 454(7204):646–650. [doi:10.1038/nature07061]PubMedCrossRefGoogle Scholar
  35. Kim, J.B., Greber, B., Araúzo-Bravo, M.J., Meyer, J., Park, K.I., Zaehres, H., Schöler, H.R., 2009a. Direct reprogramming of human neural stem cells by OCT4. Nature, 461(7264):649–653. [doi:10.1038/nature08436]PubMedCrossRefGoogle Scholar
  36. Kim, J.B., Sebastiano, V., Wu, G., Araúzo-Bravo, M.J., Sasse, P., Gentile, L., Ko, K., Ruau, D., Ehrich, M., van den Boom, D., et al., 2009b. Oct4-induced pluripotency in adult neural stem cells. Cell, 136(3):411–419. [doi:10. 1016/j.cell.2009.01.023]PubMedCrossRefGoogle Scholar
  37. Lacoste, A., Berenshteyn, F., Brivanlou, A.H., 2009. An efficient and reversible transposable system for gene delivery and lineage-specific differentiation in human embryonic stem cells. Cell Stem Cell, 5(3):332–342. [doi:10.1016/j.stem.2009.07.011]PubMedCrossRefGoogle Scholar
  38. Lagarkova, M.A., Shutova, M.V., Bogomazova, A.N., Vassina, E.M., Glazov, E.A., Zhang, P., Rizvanov, A.A., Chestkov, I.V., Kiselev, S.L., 2010. Induction of pluripotency in human endothelial cells resets epigenetic profile on genome scale. Cell Cycle, 9(5):937–946. [doi:10.4161/cc.9.5.10869]PubMedCrossRefGoogle Scholar
  39. Lee, G., Papapetrou, E.P., Kim, H., Chambers, S.M., Tomishima, M.J., Fasano, C.A., Ganat, Y.M., Menon, J., Shimizu, F., Viale, A., et al., 2009. Modelling pathogenesis and treatment of familial dysautonomia using patientspecific iPS cells. Nature, 461(7262):402–406. [doi:10. 1038/nature08320]PubMedCrossRefGoogle Scholar
  40. Lei, F., Haque, R., Xiong, X., Song, J., 2012. Directed differentiation of induced pluripotent stem cells towards T lymphocytes. J. Vis. Exp., 63:e3986. [doi:10.3791/3986]PubMedGoogle Scholar
  41. Li, C., Zhou, J., Shi, G., Ma, Y., Yang, Y., Gu, J., Yu, H., Jin, S., Wei, Z., Chen, F., et al., 2009. Pluripotency can be rapidly and efficiently induced in human amniotic fluid-derived cells. Hum. Mol. Genet., 18(22):4340–4349. [doi:10.1093/hmg/ddp386]PubMedCrossRefGoogle Scholar
  42. Li, W., Ding, S., 2010. Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol. Sci., 31(1):36–45. [doi:10.1016/]PubMedCrossRefGoogle Scholar
  43. Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., Hao, E., Hayek, A., Deng, H., Ding, S., 2009. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell, 4(1):16–19. [doi:10.1016/j.stem.2008.11.014]PubMedCrossRefGoogle Scholar
  44. Liao, J., Cui, C., Chen, S., Ren, J., Chen, J., Gao, Y., Li, H., Jia, N., Cheng, L., Xiao, H., et al., 2009. Generation of induced pluripotent stem cell lines from adult rat cells. Cell Stem Cell, 4(1):11–15. [doi:10.1016/j.stem.2008.11.013]PubMedCrossRefGoogle Scholar
  45. Liu, H., Zhu, F., Yong, J., Zhang, P., Hou, P., Li, H., Jiang, W., Cai, J., Liu, M., Cui, K., et al., 2008. Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell, 3(6):587–590. [doi:10.1016/j.stem.2008.10.014]PubMedCrossRefGoogle Scholar
  46. Liu, H., Ye, Z., Sharkis, S., Jang, Y.Y., 2010. Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology, 51(5):1810–1819. [doi:10.1002/hep.23626]PubMedCrossRefGoogle Scholar
  47. Loh, Y.H., Hartung, O., Li, H., Guo, C., Sahalie, J.M., Manos, P.D., Urbach, A., Heffner, G.C., Grskovic, M., Vigneault, F., et al., 2010. Reprogramming of T cells from human peripheral blood. Cell Stem Cell, 7(1):15–19. [doi:10.1016/j.stem.2010.06.004]PubMedCrossRefGoogle Scholar
  48. Maehr, R., Chen, S., Snitow, M., Ludwig, T., Yagasaki, L., Goland, R., Leibel, R.L., Melton, D.A., 2009. Generation of pluripotent stem cells from patients with type 1 diabetes. PNAS, 106(37):15768–15773. [doi:10.1073/pnas.0906894106]PubMedCrossRefGoogle Scholar
  49. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., et al., 2007. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell, 1(1):55–70. [doi:10.1016/j.stem.2007.05.014]PubMedCrossRefGoogle Scholar
  50. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N., Yamanaka, S., 2008. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol., 26(1):101–106. [doi:10.1038/nbt1374]PubMedCrossRefGoogle Scholar
  51. Nishimura, K., Sano, M., Ohtaka, M., Furuta, B., Umemura, Y., Nakajima, Y., Ikehara, Y., Kobayashi, T., Segawa, H., Takayasu, S., et al., 2010. Development of defective and persistent sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming. J. Biol. Chem., 286(6):4760–4771. [doi:10.1074/jbc.M110.183780]PubMedCrossRefGoogle Scholar
  52. Okita, K., Ichisaka, T., Yamanaka, S., 2007. Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151):313–317. [doi:10.1038/nature05934]PubMedCrossRefGoogle Scholar
  53. Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., Yamanaka, S., 2008. Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322(5903):949–953. [doi:10.1126/science.1164270]PubMedCrossRefGoogle Scholar
  54. Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., Hong, H., Nakagawa, M., Tanabe, K., Tezuka, K., et al., 2011. A more efficient method to generate integration-free human iPS cells. Nat. Methods, 8(5): 409–412. [doi:10.1038/nmeth.1591]PubMedCrossRefGoogle Scholar
  55. Park, I.H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M.W., Cowan, C., Hochedlinger, K., Daley, G.Q., 2008. Disease-specific induced pluripotent stem cells. Cell, 134(5):877–886. [doi:10.1016/j.cell.2008.07.041]PubMedCrossRefGoogle Scholar
  56. Ruiz, S., Brennand, K., Panopoulos, A.D., Herrerías, A., Gage, F.H., Izpisua-Belmonte, J.C., 2010. High-efficient generation of induced pluripotent stem cells from human astrocytes. PLoS ONE, 5(12):e15526. [doi:10.1371/journal.pone.0015526]PubMedCrossRefGoogle Scholar
  57. Seki, T., Yuasa, S., Oda, M., Eqashira, T., Yae, K., Kusumoto, D., Nakata, H., Tohyama, S., Hashimoto, H., Kodaira, M., et al., 2010. Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell, 7(1):11–14. [doi:10.1016/j.stem.2010.06.003]PubMedCrossRefGoogle Scholar
  58. Si-Tayeb, K., Noto, F.K., Sepac, A., Sedlic, F., Bosnjak, Z.J., Lough, J.W., Duncan, S.A., 2010. Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Dev. Biol., 10(1):81. [doi:10.1186/1471-213X-10-81]PubMedCrossRefGoogle Scholar
  59. Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G.W., Cook, E.G., Hargus, G., Blak, A., Cooper, O., Mitalipova, M., et al., 2009. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5):964–977. [doi:10.1016/j.cell.2009.02.013]PubMedCrossRefGoogle Scholar
  60. Stadtfeld, M., Hochedlinger, K., 2010. Induced pluripotency: history, mechanisms, and applications. Genes Dev., 24(20): 2239–2263. [doi:10.1101/gad.1963910]PubMedCrossRefGoogle Scholar
  61. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., Hochedlinger, K., 2008a. Induced pluripotent stem cells generated without viral integration. Science, 322(5903):945–949. [doi:10.1126/science.1162494]PubMedCrossRefGoogle Scholar
  62. Stadtfeld, M., Brennand, K., Hochedlinger, K., 2008b. Reprogramming of pancreatic β cells into induced pluripotent stem cells. Curr. Biol., 18(12):890–894. [doi:10.1016/j.cub.2008.05.010]PubMedCrossRefGoogle Scholar
  63. Staerk, J., Dawlaty, M.M., Gao, Q., Maetzel, D., Hanna, J., Sommer, C.A., Mostoslavsky, G., Jaenisch, R., 2010. Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell, 7(1):20–24. [doi:10.1016/j.stem.2010.06.002]PubMedCrossRefGoogle Scholar
  64. Sugii, S., Kida, Y., Kawamura, T., Suzuki, J., Vassena, R., Yin, Y.Q., Lutz, M.K., Berggren, W.T., Izpisúa Belmonte, J.C., Evans, R.M., 2010. Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. PNAS, 107(8):3558–3563. [doi:10.1073/pnas.0910172106]PubMedCrossRefGoogle Scholar
  65. Sun, N., Panetta, N.J., Gupta, D.M., Wilson, K.D., Lee, A., Jia, F., Hu, S., Cherry, A.M., Robbins, R.C., Longaker, M.T., et al., 2009. Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. PNAS, 106(37):15720–15725. [doi:10.1073/pnas.0908450106]PubMedCrossRefGoogle Scholar
  66. Takahashi, K., Yamanaka, S., 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4):663–676. [doi:10.1016/j.cell.2006.07.024]PubMedCrossRefGoogle Scholar
  67. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S., 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5):861–872. [doi:10.1016/j.cell.2007.11.019]PubMedCrossRefGoogle Scholar
  68. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swierqiel, J.J., Marshall, V.S., Jones, J.M., 1998. Embryonic stem cell lines derived from human blastocysts. Science, 282(5391):1145–1147. [doi:10.1126/science.282.5391.1145]PubMedCrossRefGoogle Scholar
  69. Tsai, S.Y., Clavel, C., Kim, S., Ang, Y.S., Grisanti, L., Lee, D.F., Kelley, K., Rendl, M., 2010. Oct4 and klf4 reprogram dermal papilla cells into induced pluripotent stem cells. Stem Cells, 28(2):221–228. [doi:10.1002/stem.281]PubMedGoogle Scholar
  70. Utikal, J., Maherali, N., Kulalert, W., Hochedlinger, K., 2009. Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J. Cell Sci., 122(19):3502–3510. [doi:10.1242/jcs.054783]PubMedCrossRefGoogle Scholar
  71. Warren, L., Manos, P.D., Ahfeldt, T., Loh, Y.H., Li, H., Lau, F., Ebina, W., Mandal, P.K., Smith, Z.D., Meissner, A., et al., 2010. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 7(5):618–630. [doi:10. 1016/j.stem.2010.08.012]PubMedCrossRefGoogle Scholar
  72. Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B.E., Jaenisch, R., 2007. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448(7151):318–324. [doi:10.1038/nature05944]PubMedCrossRefGoogle Scholar
  73. Wernig, M., Lengner, C.J., Hanna, J., Lodato, M.A., Steine, E., Foreman, R., Staerk, J., Markoulaki, S., Jaenisch, R., 2008. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat. Biotechnol., 26(8):916–924. [doi:10.1038/nbt1483]PubMedCrossRefGoogle Scholar
  74. Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J., Campbell, K.H., 1997. Viable offspring derived from fetal and adult mammalian cells. Nature, 385(6619):810–813. [doi:10. 1038/385810a0]PubMedCrossRefGoogle Scholar
  75. Woltjen, K., Michael, I.P., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R., Cowling, R., Wang, W., Liu, P., Gertsenstein, M., et al., 2009. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458(7239):766–770. [doi:10.1038/nature07863]PubMedCrossRefGoogle Scholar
  76. Wu, Y., Zhang, Y., Mishra, A., Tardif, S.D., Hornsby, P.J., 2010. Generation of induced pluripotent stem cells from newborn marmoset skin fibroblasts. Stem Cell Res., 4(3): 180–188. [doi:10.1016/j.scr.2010.02.003]PubMedCrossRefGoogle Scholar
  77. Wu, Z., Chen, J., Ren, J., Bao, L., Liao, J., Cui, C., Rao, L., Li, H., Gu, Y., Dai, H., et al., 2009. Generation of pig induced pluripotent stem cells with a drug-inducible system. J. Mol. Cell Biol., 1(1):46–54. [doi:10.1093/jmcb/mjp003]PubMedCrossRefGoogle Scholar
  78. Yakubov, E., Rechavi, G., Rozenblatt, S., Givol, D., 2010. Reprogramming of human fibroblasts to pluripotent stem cells using mRNA of four transcription factors. Biochem. Biophys. Res. Commun., 394(1):189–193. [doi:10.1016/j.bbrc.2010.02.150]PubMedCrossRefGoogle Scholar
  79. Yamanaka, S., 2012. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell, 10(6):678–684. [doi:10.1016/j.stem.2012.05.005]PubMedCrossRefGoogle Scholar
  80. Ye, L., Chang, J.C., Lin, C., Sun, X., Yu, J., Kan, Y.W., 2009. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. PNAS, 106(24): 9826–9830. [doi:10.1073/pnas.0904689106]PubMedCrossRefGoogle Scholar
  81. Ye, Z., Zhan, H., Mali, P., Dowey, S., Williams, D.M., Jang, Y.Y., Dang, V.L., Spivak, J.L., Moliterno, A.R., Cheng, L., 2009. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood, 114(27):5473–5480. [doi:10.1182/blood-2009-04-217406]PubMedCrossRefGoogle Scholar
  82. Ying, Q.L., Nichols, J., Evans, E.P., Smith, A.G., 2002. Changing potency by spontaneous fusion. Nature, 416(6880):545–548. [doi:10.1038/nature729]PubMedCrossRefGoogle Scholar
  83. Yu, J., Vodyanik, M.K., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., et al., 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858):1917–1920. [doi:10.1126/science.1151526]PubMedCrossRefGoogle Scholar
  84. Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, I.I., Thomson, J.A., 2009. Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324(5928):797–801. [doi:10.1126/science.1172482]PubMedCrossRefGoogle Scholar
  85. Zhang, J., Zhao, J., Jiang, W.J., Shan, X.W., Yang, X.M., Gao, J.G., 2012. Conditional gene manipulation: Cre-ating a new biological ear. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 13(7):511–524. [dio:10.1631/jzus.B1200042]CrossRefGoogle Scholar
  86. Zhao, H.X., Li, Y., Jin, H.F., Xie, L., Liu, C., Jiang, F., Luo, Y.N., Yin, G.W., Li, Y., Wang, J., et al., 2010. Rapid and efficient reprogramming of human amnion-derived cells into pluripotency by three factors OCT4/SOX2/NANOG. Differentiation, 80(2–3):123–129. [doi:10.1016/j.diff.2010.03.002]PubMedCrossRefGoogle Scholar
  87. Zhao, X.Y., Li, W., Lv, Z., Liu, L., Tong, M., Hai, T., Hao, J., Guo, C.L., Ma, Q.W., Wang, L., et al., 2009. iPS cells produce viable mice through tetraploid complementation. Nature, 461(7260):86–90. [doi:10.1038/nature08267]PubMedCrossRefGoogle Scholar
  88. Zhou, H., Wu, S., Joo, J.Y., Zhu, S., Han, D.W., Lin, T., Trauger, S., Bien, G., Yao, S., Zhu, Y., et al., 2009. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell, 4(5):381–384. [doi:10.1016/j.stem.2009.04.005]PubMedCrossRefGoogle Scholar
  89. Zhou, W., Freed, C.R., 2009. Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells, 27(11):2667–2674. [doi:10.1002/stem.201]PubMedCrossRefGoogle Scholar
  90. Zhu, Y., Hu, H.L., Li, P., Yang, S., Zhang, W., Ding, H., Tian, R.H., Ning, Y., Zhang, L.L., Guo, X.Z., et al., 2012. Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study. Asian J. Androl., 14(4):574–579. [doi:10.1038/aja.2012.3]PubMedCrossRefGoogle Scholar

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© Zhejiang University and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.School of Life SciencesShandong UniversityJinanChina

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