Open Access
Review (Published online: 14-06-2017)
12. Induced pluripotent stem cell: A headway in reprogramming with promising approach in regenerative biology
N. Rawat and M. K. Singh
Veterinary World, 10(6): 640-649

N. Rawat: Embryo Biotechnology Lab, Animal Biotechnology Centre, ICAR - National Dairy Research Institute, Karnal - 132 001, Haryana, India.
M. K. Singh: Embryo Biotechnology Lab, Animal Biotechnology Centre, ICAR - National Dairy Research Institute, Karnal - 132 001, Haryana, India.

doi: 10.14202/vetworld.2017.640-649

Share this article on [Facebook] [LinkedIn]

Article history: Received: 04-02-2017, Accepted: 26-04-2017, Published online: 14-06-2017

Corresponding author: M. K. Singh

E-mail: drmanojvet@gmail.com

Citation: Rawat N, Singh MK (2017) Induced pluripotent stem cell: A headway in reprogramming with promising approach in regenerative biology, Veterinary World, 10(6): 640-649.
Abstract

Since the embryonic stem cells have knocked the doorsteps, they have proved themselves in the field of science, research, and medicines, but the hovered restrictions confine their application in human welfare. Alternate approaches used to reprogram the cells to the pluripotent state were not up to par, but the innovation of induced pluripotent stem cells (iPSCs) paved a new hope for the researchers. Soon after the discovery, iPSCs technology is undergoing renaissance day by day, i.e., from the use of genetic material to recombinant proteins and now only chemicals are employed to convert somatic cells to iPSCs. Thus, this technique is moving straightforward and productive at an astonishing pace. Here, we provide a brief introduction to iPSCs, the mechanism and methods for their generation, their prevailing and prospective applications and the future opportunities that can be expected from them.

Keywords: cellular reprogramming, embryonic stem cells, induced pluripotent stem cells, stem cells.

References

1. Martello, G. and Smith, A. (2014) Nature of embryonic stem cells annual review of cell and developmental biology. Cell. Dev. Biol., 30: 647-675. [Crossref] [PubMed]

2. Bernard, L. and Lindsay, P. (2009) Ethical issues in stem cell research. Endocr. Rev., 30(3): 204-213. [Crossref] [PubMed] [PMC]

3. Wilmut, I., Schnieke, A.E., Mcwhir, J., Kind, A.J. and Campbell, K.H.S. (1997) Viable offspring derived from fetal and adult mammalian cells. Nature, 385: 810-813. [Crossref] [PubMed]

4. Silva, J., Chambers, I., Pollard, S. and Smith, A. (2006) Nanog promotes transfer of pluripotency after cell fusion. Nature, 441: 997-1001. [Crossref] [PubMed]

5. Pralong, D., Trounson, A.O. and Verma, P.J. (2006) Cell fusion for reprogramming pluripotency: Toward elimination of the pluripotent genome. Stem Cell Rev., 2(4): 331-340. [Crossref]

6. Yamanaka, S. and Blau, H.M. (2010) Nuclear reprogramming to a pluripotent state by three approaches. Nature, 465(7299): 704-712. [Crossref] [PubMed] [PMC]

7. Bilic, J., Carlos, J. and Belmonte, I. (2011) Concise review: Induced pluripotent stem cells versus embryonic stem cells: Close enough or yet too far apart? Stem Cells, 30(1): 33-41. [Crossref] [PubMed]

8. Joo, J.Y., Choi, H.W., Kim, M.J., Zaehres, H., Tapia, N., Stehling, M., Jung, K.S., Do, J.T. and Scholer, H.R. (2014) Establishment of a primed pluripotent epiblast stem cell in FGF4-based conditions. Sci. Rep., 4: 7477. [Crossref] [PubMed] [PMC]

9. Weinberger, L., Ayyash, M., Novershtern, N. and Hanna, J.H. (2016) Dynamic stem cell states: Naive to primed pluripotency in rodents and humans. Nat. Rev. Mol. Cell. Biol., 17: 155-169. [Crossref] [PubMed]

10. Li, X., Pei, D. and Zheng, H. (2014) Transitions between epithelial and mesenchymal states during cell fate conversions. Prote. Cell, 5(8): 580-591. [Crossref] [PubMed] [PMC]

11. Hawkins, K., Joy, S. and McKay, T. (2014) Cell signalling pathways underlying induced pluripotent stem cell reprogramming. World J. Stem Cells., 6(5): 620-628. [Crossref] [PubMed] [PMC]

12. Maherali, N. and Hochedlinger, K. (2009) TGF beta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr Biol., 19: 1718-1723. [Crossref] [PubMed] [PMC]

13. Jiao, J., Dang, Y., Yang, Y., Gao, R., Zhang, Y., Kou, Z., Sun, X.F. and Gao, S. (2013) Promoting reprogramming by FGF2 reveals that the extracellular matrix is a barrier for reprogramming fibroblasts to pluripotency. Stem Cells, 31: 729-740. [Crossref] [PubMed]

14. Chambers, I. and Tomlinson, S.R. (2009) The transcriptional foundation of pluripotency. Development, 136: 2311-2322. [Crossref] [PubMed] [PMC]

15. Niwa, H., Miyazaki, J. and Smith, A.G. (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet., 24: 372-376. [Crossref] [PubMed]

16. 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. [Crossref] [PubMed]

17. Okita, K, Ichisaka, T. and Yamanaka, S. (2007) Generation of germline-competent induced pluripotent stem cells. Nature, 448: 313-317. [Crossref] [PubMed]

18. Wernig, M. (2007) In vitro reprogrammed fibroblasts have a similar developmental potential as ES cells and an ES cell-like epigenetic state. Nature, 448: 313-317. [Crossref] [PubMed]

19. Du, D. and Lou, X. (2014) Generation of induced pluripotent stem cells from neonatal mouse cochlear cells. Differentiation, 87: 127-133. [Crossref] [PubMed]

20. Koh, S. and Piedrahita, J.A. (2015) Generation of induced pluripotent stem cells (iPSCs) from adult canine fibroblasts methods. Mol. Biol., 1330: 69-78.

21. Esteban, M.A., Xu, J., Yang, J., Peng, M., Qin, D., Li, W., Jiang, Z., Chen, J., Deng, K., Zhong, M., Cai, J., Lai, L. and Pei, D. (2009) Generation of induced pluripotent stem cell lines from Tibetan miniature pig. J. Biol. Chem., 284(26): 17634-17640. [Crossref] [PubMed] [PMC]

22. Fujishiro, S.H., Nakano, K., Mizukami, Y., Azami, T., Arai, Y., Matsunari, H., Ishino, R., Nishimura, T., Watanabe, M., Abe, T., Furukawa, Y., Umeyama, K., Yamanaka, S., Ema, M., Nagashima, H. and Hanazono, Y. (2013) Generation of naive-like porcine-induced pluripotent stem cells capable of contributing to embryonic and fetal development. Stem Cells Dev., 22(3): 473-482. [Crossref] [PubMed] [PMC]

23. Han, X., Han, J., Ding, F., Cao, S., Lim, S.S., Dai, Y., Zhang, R., Zhang, Y., Lim, B. and Li, N. (2011) Generation of induced pluripotent stem cells from bovine embryonic fibroblast cells. Cell Res., 21: 1509-1512. [Crossref] [PubMed] [PMC]

24. Deng, Y., Liu, Q., Luo, C., Chen, S., Li, X., Wang, C., Liu, Z., Lei, X., Zhang, H., Sun, H., Lu, F., Jiang, J. and Shi, D. (2012) Generation of induced pluripotent stem cells from buffalo (Bubalus bubalis) fetal fibroblasts with buffalo defined factors. Stem Cells Dev., 21(13): 2485-2494. [Crossref] [PubMed]

25. Imamura, M., Okuno, H., Tomioka, I., Kawamura, Y., Lin, Z.Y., Nakajima, R., Akamatsu, W., Okano, J., Matsuzaki, Y., Sasaki, E. and Okano, H. (2012) Derivation of induced pluripotent stem cells by retroviral gene transduction in mammalian species. Methods Mol. Biol., 925: 21-48. [Crossref] [PubMed]

26. 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(5): 861-872. [Crossref] [PubMed]

27. Ninagawa, N.T., Kawabata, Y., Watanabe, S., Nagata, K. and Torihashi, S. (2014) Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome. Plos One, 9(8): e104462. [Crossref] [PubMed] [PMC]

28. Honda, A., Hatori, M., Hirose, M., Honda, C., Izu, H., Inoue, K., Hirasawa, R., Matoba, S., Togayachi, S., Hiroyuki, M. and Atsuo, O. (2013) Naive-like conversion overcomes the limited differentiation capacity of induced pluripotent stem cells. J. Biol. Chem., 288(36): 26157-26166. [Crossref] [PubMed] [PMC]

29. Sandmaier, S.E., Nandal, A., Powell, A., Garrett, W., Blomberg, L., Donovan, D.M., Talbot, N. and Telugu, B.P. (2015) Generation of induced pluripotent stem cells from domestic goats. Mol. Reprod. Dev., 82(9): 709-721. [Crossref] [PubMed]

30. Cao, H., Yang, P., Pu, Y., Sun, X., Yin, H., Zhang, Y., Zhang, Y., Li, Y., Liu, Y., Fang, F., Zhang, Z., Tao, Y. and Zhang, X. (2012) Characterization of bovine induced pluripotent stem cells by lentiviral transduction of reprogramming factor fusion proteins. Int. J. Biol. Sci., 8(4): 498-511. [Crossref] [PubMed] [PMC]

31. Wang, J., Gu, Q., Hao, J., Bai, D., Liu, L., Zhao, X., Liu, Z., Wang, L. and Zhou, Q. (2013) Generation of induced pluripotent stem cells with high efficiency from human umbilical cord blood mononuclear cells. Dev. Reprod. Biol., 11(5): 304-311. [Crossref]

32. Sommer, C.A., Sommer, A.G., Longmire, T.A., Christodoulou, C., Thomas, D.D., Gostissa, M., Alt, F.W., Murphy, G.J., Kotton, D.N. and Mostoslavsky, G. (2.010) Excision of reprogramming transgenes improves the differentiation potential of iPS cells generated with a single excisable vector. Stem Cells, 28(1): 64-74. [PubMed] [PMC]

33. Meng, F., Wang, X., Gu, P., Wang, Z. and Guo, W. (2013) Induction of retinal ganglion-like cells from fibroblasts by adenoviral gene delivery. Neuroscience, 250: 381-393. [Crossref] [PubMed]

34. Fujie, Y., Fusaki, N., Katayama, T., Hamasaki, M., Soejima, Y., Soga, M., Ban, H., Hasegawa, M., Yamashita, S., Kimura, S., Suzuki, S., Matsuzawa, T., Akari, H. and Takumi, E. (2014) New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood. PLoS One, 9(12): e113052. [Crossref]

35. Kishino, Y., Seki, T., Yuasa, S., Fujita, J. and Fukuda, K. (2015) Generation of induced pluripotent stem cells from human peripheral T cells using Sendai virus in feeder-free conditions. J. Vis. Exp., 11(105): e53225. [Crossref]

36. Xue, Y., Cai, X., Wang, L., Liao, B., Zhang, H., Shan, Y., Chen, Q., Zhou, T., Li, X., Hou, J., Chen, S., Luo, R., Qin, D., Pei, D. and Pan, G. (2013) Generating a non-integrating human induced pluripotent stem cell bank from urine-derived cells. PLoS One, 8(8): e70573. [Crossref]

37. Wen, W., Zhang, J., Xu, J., Su, R.J., Neises, A., Ji, G.Z., Yuan, W., Cheng, T. and Zhang, X.B. (2016) Enhanced generation of integration-free iPSCs from human adult peripheral blood mononuclear cells with an optimal combination of episomal vectors. Stem Cell Rep., 6(6): 873-884. [Crossref] [PubMed] [PMC]

38. Meraviglia, V., Zanon, A., Lavdas, A.A., Schwienbacher, C., Silipigni, R., Segni, M., Chen, H.S., Pramstaller, P.P., Hicks, A.A. and Rossini, A. (2015) Generation of induced pluripotent stem cells from frozen buffy coats using non-integrating episomal plasmids. J. Vis. Exp., 5(100): e52885. [Crossref]

39. Talluri, T.R., Kumar, D., Glage, S., Garrels, W., Ivics, Z., Debowski, K., Behr, R., Niemann, H. and Kues, W.A. (2015) Derivation and characterization of bovine induced pluripotent stem cells by transposon-mediated reprogramming. Cell Reprogram., 17(2): 131-140. [Crossref] [PubMed] [PMC]

40. Mo, X., Li, N. and Wu, S. (2014) Generation and characterization of bat-induced pluripotent stem cells. Theriogenology, 82(2): 283-293. [Crossref] [PubMed]

41. Choi, H.Y., Lee, T.J., Yang, G.M., Oh, J., Won, J., Han, J., Jeong, G.J., Kim, J., Kim, J.H., Kim, B.S. and Cho, S.G. (2016) Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells. J. Controll Release, 235: 222-235. [Crossref] [PubMed]

42. Preskey, D., Allison, T.F., Jones, M., Mamchaoui, K. and Unger, C. (2016) Synthetically modified mRNA for efficient and fast human iPS cell generation and direct trans differentiation to myoblasts. Biochem. Biophys. Res. Commun., 473(3): 743-751. [Crossref] [PubMed]

43. Yoshioka, N., Gros, E., Li, R., Kumar, S., Deacon, D.C., Maron, C., Muotri, A.R., Chi, N.C., Fu, X.D., Yu, B.D. and Dowdy, S.F. (2013) Efficient generation of human iPS cells by a synthetic self replicative RNA. Cell Stem Cell, 13(2): 246-254. [Crossref] [PubMed] [PMC]

44. Nemes, C., Varga, E., Polgar, Z., Klincumhom, N., Pirity, M.K. and Dinnyes, A. (2014) Generation of mouse induced pluripotent stem cells by protein transduction. Tissue Eng. Methods, 20(5): 383-392. [Crossref] [PubMed] [PMC]

45. Khan, M., Narayana, K., Lu, H., Choo, Y., Du, C., Wiradharma, N., Yang, Y.Y. and Wan, A.C. (2013) Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector. Biomaterials, 34: 5336-5343. [Crossref] [PubMed]

46. Cho, S.J., Choi, H.W., Cho, J., Jung, S., Seo, H.G. and Do, J.T. (2013) Activation of pluripotency genes by a nanotube-mediated protein delivery system. Mol. Reprod., 80(12): 1000-1008. [Crossref] [PubMed]

47. Hirai, H., Firpo, M. and Kikyo, N. (2012) Establishment of LIF-dependent human iPS cells closely related to basic FGF-dependent authentic iPS cells. PLoS One, 7(6): e39022. [Crossref]

48. Mohyeldin, A., Garzon, M.T. and Quinones, H.A. (2010) Oxygen in stem cell biology: A critical component of the stem cell niche. Cell Stem Cell, 7(2): 150-161. [Crossref] [PubMed]

49. Zhang, Z. and Wu, W.S. (2013) Sodium butyrate promotes generation of human induced pluripotent stem cells through induction of the miR302/367 cluster. Stem Cells Dev., 22: 2268-2277. [Crossref] [PubMed] [PMC]

50. Hou, P., Li, Y., Zhang, X., Liu, C., Guan, J., Li, H., Zhao, T., Ye, J., Yang, W. and Liu, K. (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science, 341: 651-654. [Crossref] [PubMed]

51. Wu, Y.L., Pandian, G.N., Ding, Y.P., Zhang, W., Tanaka, Y. and Sugiyama, H. (2013) Clinical grade iPS cells: Need for versatile small molecules and optimal cell sources. Chem. Biol., 20: 1311-1322. [Crossref]

52. Ichida, J.K., Blanchard, J., Lam, K., Son, E.Y., Chung, J.E., Egli, D., Loh, K.M., Carter, A.C., Giorgio, K.K., Huangfu, D., Akutsu, H., Liu, D.R., Rubin, L.L. and Eggan, K. (2009) A small molecule inhibitor of TGF-β signaling replaces Sox2 in reprogramming by inducing nanog. Cell Stem Cell, 5(5): 491-503. [Crossref] [PubMed] [PMC]

53. Wang, Y., Liang, P., Lan, F., Wu, H., Lisowski, L., Gu, M., Hu, S., Kay, M.A., Urnov, F.D. and Shinnawi, R. (2014) Genome editing of isogenic human induced pluripotent stem cells recapitulates long QT phenotype for drug testing. J. Am. Coll. Cardiol., 64: 451-459. [Crossref] [PubMed] [PMC]

54. Li, D., Wang, L., Hou, J., Shen, Q., Chen, Q., Wang, X., Du, J., Cai, X., Shan, Y., Zhang, T., Zhou, T., Shi, X., Li, Y., Zhang, H. and Guangjin, P. (2016) Optimized approaches for generation of integration-free iPSCs from human urine-derived cells with small molecules and autologous feeder. Stem Cell Rep., 6: 717-728. [Crossref] [PubMed] [PMC]

55. Lin, T., Ambasudhan, R., Yuan, X., Li, W., Hilcove, S., Abujarour, R., Lin, X., Hahm, H.S., Hao, E. and Hayek, A. (2009) A chemical platform for improved induction of human iPSCs. Nat. Methods, 6: 805-808. [Crossref] [PubMed] [PMC]

56. Shi, Y., Desponts, C., Do, J.T., Hahm, H.S., Scholer, H.R. and Ding, S. (2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by October 4 and Klf4 with small-molecule compounds. Cell Stem Cell, 3(5): 568-574. [Crossref] [PubMed]

57. Pandian, G.N., Sato, S., Anandha, K., Taniguchi, J., Takashima, K., Syed, J., Han, L., Saha, A., Bando, T. and Nagase, H. (2014) Identification of a small molecule that turns on the pluripotency gene circuitry in human fibroblasts. ACS Chem. Biol., 9: 2729-2736. [Crossref] [PubMed]

58. Debeb, B.G., Lacerda, L., Xu, W., Larson, R., Solley, T., Atkinson, R., Sulman, E.P., Ueno, N.T., Krishnamurthy, S., Reuben, J.M., Buchholz, T.A. and Woodward, W.A. (2012) Histone deacetylase inhibitors stimulate dedifferentiation of human breast cancer cells through WNT/β-catenin signalling. Stem Cells, 30(11): 2366-2377. [Crossref] [PubMed] [PMC]

59. Zhai, Y., Chen, X., Yu, D., Li, T., Cui, J., Wang, G., Hu, J.F. and Li, W. (2015) Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress. Exp. Cell Res., 337: 61-67. [Crossref] [PubMed]

60. Vazquez, M.A., Corominas, F.B., Cufi, S., Vellon, L., Oliveras, F.C., Menendez, O.J., Joven, J., Lupu, R. and Menendez, J.A. (2013) The mitochondrial H(+)-ATP synthase and the lipogenic switch: New core components of metabolic reprogramming in induced pluripotent stem (iPS) cells. Cell Cycle, 12(2): 207-18. [Crossref] [PubMed] [PMC]

61. Bernhardt, M., Galach, M., Novak, D. and Utikal, J. (2012) Mediators of induced pluripotency and their role in cancer cells-current scientific knowledge and future perspectives. Biotechnol. J., 7: 810-821. [Crossref] [PubMed]

62. Lee, D.F., Su, J., Kim, H.S., Chang, B., Papatsenko, D., Zhao, R., Yuan, Y., Gingold, J., Xia, W., Darr, H., Mirzayans, R., Hung, M.C., Schanie, C., Ihor, R. and Lemischka, I.R. (2015) Modeling familial cancer with induced pluripotent stem cells. Cell, 161(2): 240-254. [Crossref] [PubMed] [PMC]

63. Berdasco, M. and Esteller, M. (2010) Aberrant epigenetic landscape in cancer: How cellular identity goes awry. Dev. Cell., 19: 698-711. [Crossref]

64. Lin, S.L., Chang, D.C. and Chang, L.S. (2008) Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA, 14: 2115-2124. [Crossref] [PubMed] [PMC]

65. 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. [Crossref] [PubMed] [PMC]

66. Miyoshi, N., Ishii, H. and Nagai, K. (2010) Defined factors induce reprogramming of gastrointestinal cancer cells. Proc. Natl. Acad. Sci., 107: 40-45. [Crossref] [PubMed] [PMC]

67. Carette, J.E., Pruszak, J., Varadarajan, M. (2010) Generation of iPSCs from cultured human malignant cells. Blood, 115: 4039-4042. [Crossref] [PubMed] [PMC]

68. Mathieu, J., Zhang, Z. and Zhou, W. (2011) HIF induces human embryonic stem cell markers in cancer cells. Cancer Res., 71: 4640-4652. [Crossref] [PubMed] [PMC]

69. Corominas, F.B., Cufi, S. and Oliveras, F.C. (2013) Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway. Cell Cycle, 12: 3109-3124. [Crossref] [PubMed] [PMC]

70. Stricker, S.H., Feber, A. and Engstrom, P.G. (2013) Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behaviour in a lineage-dependent manner. Genes Dev., 27: 654-669. [Crossref] [PubMed] [PMC]

71. Zhang, J. (2011) A human iPSC model of hutchinson gilford progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell, 8(1): 31-45. [Crossref] [PubMed]

72. Broxmeyer, H.E. (2010) Will iPS cells enhance therapeutic applicability of cord blood cells and banking? Cell Stem Cell, 6: 21-24. [Crossref] [PubMed]

73. Hanna, J., Wernig, M., Markoulaki, S., Sun, C.W., Meissner, A., Cassady, J.P., Beard, C., Brambrink, T., Wu, L.C., Townes, T.M. and Jaenisch, R. (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858): 1920-1923. [Crossref]

74. Tsuji, O., Miura, K., Okada, Y., Fujiyoshi, K., Mukaino, M., Nagoshi, N., Kitamura, K., Kumagai, G., Nishino, M. and Tomisato, S. (2010) Therapeutic potential of appropriately evaluated safe induced pluripotent stem cells for spinal cord injury. Proc. Natl. Acad. Sci., 107: 12704-12709. [Crossref] [PubMed] [PMC]

75. Wernig, M., Zhao, J.P., Pruszak, J., Hedlund, E., Fu, D., Soldner, F., Broccoli, V., Paton, M., Isacson, O. and Jaenisch, R. (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc. Natl. Acad. Sci., 105: 5856-5861. [Crossref] [PubMed] [PMC]

76. Swistowski, A., Peng, J., Liu, Q., Mali, P., Rao, M.S., Cheng, L. and Zeng, X. (2010) Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells, 28: 1893-1904. [Crossref] [PubMed] [PMC]

77. Xu, D., Alipio, Z., Fink, L.M., Adcock, D.M., Yang, J., Ward, D.C. and Ma, Y. (2009) Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc. Natl. Acad. Sci., 106: 808-813. [Crossref] [PubMed] [PMC]

78. Kang, S., Xia, J.C. and Lai, W. (2010) Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation, 121: 1113-1123. [Crossref] [PubMed]

79. Nelson, T.J., Martinez, F.A., Yamada, S., Perez, T.C., Ikeda, Y. and Terzic, A. (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation, 120: 408-416. [Crossref] [PubMed] [PMC]

80. Funakoshi, S., Miki, K., Takaki, T., Okubo, C., Hatani, T., Chonabayashi, K., Nishikawa, M., Takei, I., Oishi, A., Narita, M., Hoshijima, M., Kimura, T., Yamanaka, S. and Yoshida, Y. (2016) Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes. Sci. Rep., 6: 19111. [Crossref] [PubMed] [PMC]

81. Rufaihah, A.J., Huang, N.F., Jame, S., Lee, J.C., Nguyen, H.N., Byers, B., De, A., Okogbaa, J., Rollins, M. and Reijo, R. (2011) Endothelial cells derived from human iPSCS increase capillary density and improve perfusion in a mouse model of peripheral arterial disease. Arterioscler Thromb. Vasc. Biol., 31: 72-79. [Crossref] [PubMed] [PMC]

82. 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 pancreatic β-like cells. Proc. Natl. Acad. Sci., 107(30): 13426-13431. [Crossref] [PubMed] [PMC]

83. 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(82): 82-39. [Crossref]

84. Garber, K. (2015) RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat. Biotechnol., 33: 890-891. [Crossref] [PubMed]

85. Urbach, A. (2010) Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell, 6(5): 407-411. [Crossref] [PubMed] [PMC]

86. Tolar, J., Park, I.H., Xia, L., Lees, C.J., Peacock, B., Webber, B., McElmurry, R.T., Eide, C.R., Orchard, P.J., Kyba, M., Osborn, M.J., Lund, T.C., Wagner, J.E., Daley, G.Q. and Blazar, B.R. (2011) Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome). Blood, 117(3): 839-847. [Crossref] [PubMed] [PMC]

87. Liu, H. (2010) Generation of endoderm derived human induced pluripotent stem cells from primary hepatocytes. Hepatology, 51(5): 1810-1819. [Crossref] [PubMed] [PMC]

88. Sullivan, G.J. (2010) Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology, 51(1): 329-335. [Crossref] [PubMed] [PMC]

89. Li, Z., Hu, S., Ghosh, Z., Han, Z. and Wu, J.C. (2011) Functional characterization and expression profiling of human induced pluripotent stem cell and embryonic stem cell derived endothelial cells. Stem Cells Dev., 20(10): 1701-1710. [Crossref] [PubMed] [PMC]

90. Dimos, J.T. (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893): 1218-1221. [Crossref]

91. Ebert, A.D., Yu, J., Rose, F.F., Mattis, V.B., Lorson, C.L., Thomson, J.A. and Svendsen, C.N. (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457: 277-280. [Crossref] [PubMed] [PMC]

92. Marchetto, M.C. (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell, 143(4): 527-539. [Crossref] [PubMed] [PMC]

93. Chamberlain, S.J. (2010) Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader Willi syndromes. Proc. Natl. Acad. Sci., 107(41): 17668-17673. [Crossref] [PubMed] [PMC]

94. Narsinh, K., Narsinh, K.H. and Wu, J.C. (2011) Derivation of human induced pluripotent stem cells for cardiovascular disease modelling. Circ. Res., 108(9): 1146-1156. [Crossref] [PubMed] [PMC]

95. Yazawa, M., Hsueh, B., Jia, X., Pasca, A.M., Bernstein, J.A., Hallmayer, J. and Dolmetsch, R.E. (2011) Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature, 471: 230-234. [Crossref] [PubMed] [PMC]

96. Ebert, A.D., Liang, P. and Wu, J.C. (2012) Induced pluripotent stem cells as a disease modelling and drug screening platform. J Cardiovasc. Pharmacol., 60: 408-416. [Crossref] [PubMed] [PMC]

97. Lan, F., Lee, A.S., Liang, P., Sanchez, V., Nguyen, P.K., Wang, L., Han, L., Yen, M., Wang, Y. and Sun, N. (2013) Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. Cell Stem Cell, 12: 101-113. [Crossref] [PubMed] [PMC]

98. Ye, L., Chang, J.C., Lin, C., Sun, X., Yu, J. and 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. Proc. Natl. Acad. Sci., 106(24): 9826-9830. [Crossref] [PubMed] [PMC]

99. Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G.W., Cook, E.G., Hargus, G., Blak, A., Cooper, O. and Mitalipova, M. (2009) Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5): 964-977. [Crossref] [PubMed] [PMC]

100. Kang, J., Tang, B. and Guo, J. (2016) The progress of induced pluripotent stem cells as models of Parkinson's disease. Stem Cells Int., 2016: Article ID: 4126214, 1-6.

101. Sato, Y., Kobayashi, H., Higuchi, T., Shimada, Y., Era, T., Kimura, S., Eto, Y., Ida, H. and Ohashi, T. (2015) Disease modelling and lentiviral gene transfer in patient specific induced pluripotent stem cells from late onset Pompe disease patient. Mol. Ther. Methods Clin. Dev., 2: 15023. [Crossref] [PubMed] [PMC]

102. Hotta, A., Cheung, A.Y., Farra, N., Vijayaragavan, K., Seguin, C.A., Draper, J.S., Pasceri, P., Maksakova, I.A., Mager, D.L., Rossant, J., Bhatia, M. and Ellis, J. (2009) Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat. Methods, 6(5): 370-376. [Crossref] [PubMed]

103. Park, I.H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M.W., Cowan, C., Hochedlinger, K. and Daley, G.Q. (2008) Disease-specific induced pluripotent stem (iPS) cells. Cell, 134(5): 877-886. [Crossref] [PubMed] [PMC]

104. Carvajal, V.X., Sevilla, A., D'Souza, S.L., Ang, Y.S., Schaniel, C., Lee, D.F., Yang, L., Kaplan, A.D., Adler, E.D. and Rozov, R. (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature, 465: 808-812. [Crossref] [PubMed] [PMC]

105. Ebert, A.D., Kodo, K., Liang, P., Wu, H., Huber, B.C., Riegler, J., Churko, J., Lee, J., Almeida, P. and Lan, F. (2014) Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system. Sci. Transl. Med., 6: 255. [Crossref]

106. Ebert, A.D., Diecke, S., Chen, I.Y. and Wu, J.C. (2015) Reprogramming and transdifferentiation for cardiovascular development and regenerative medicine: Where do we stand? EMBO Mol. Med., 7(9): 1090-1103. [Crossref]

107. Kim, C., Wong, J., Wen, J., Wang, S., Wang, C., Spiering, S., Kan, N.G., Forcales, S., Puri, P.L. and Leone, T.C. (2013) Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature, 494: 105-110. [Crossref] [PubMed] [PMC]

108. Asimaki, A., Kapoor, S., Plovie, E., Karin, A.A., Adams, E., Liu, Z., James, C.A., Judge, D.P., Calkins, H. and Churko, J. (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci. Transl. Med., 6(240): 261-266. [Crossref]

109. Moretti, A., Bellin, M., Welling, A., Jung, C.B., Lam, J.T., Bott, F.L., Dorn, T., Goedel, A., Hohnke, C. and Hofmann, F. (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N. Engl. J. Med., 363: 1397-1409. [Crossref] [PubMed]

110. Itzhaki, I., Maizels, L., Huber, I., Dantsis, L., Caspi, O., Winterstern, A., Feldman, O., Gepstein, A., Arbel, G. and Hammerman, H. (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471: 225-229. [Crossref] [PubMed]

111. Sun, N., Yazawa, M., Liu, J., Han, L., Sanchez, F.V., Abilez, O.J., Navarrete, E.G., Hu, S., Wang, L. and Lee, A. (2012) Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Sci. Transl. Med., 4(130): 130-147. [Crossref]

112. Sharma, A., Marceau, C., Hamaguchi, R., Burridge, P.W., Rajarajan, K., Churko, J.M., Wu, H., Sallam, K.I., Matsa, E. and Sturzu, A.C. (2014) Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform. Circ. Res., 115: 556-566. [Crossref]

113. Dick, E. (2010) Evaluating the utility of cardiomyocytes from human pluripotent stem cells for drug screening. Biochem. Soc. Trans., 38(4): 1037-1045. [Crossref] [PubMed]

114. Zhao, J., Jiang, W.J., Chen, S., Hou, C.Z., Yang, X.M. and Gao, J.G. (2013) Induced pluripotent stem cells: Origins, applications, and future perspectives. Biomed. Biotechnol., 14(12): 1059-1069. [Crossref]

115. Lee, G., Papapetrou, E.P., Kim, H., Chambers, S.M., Tomishima, M.J., Fasano, C.A., Ganat, Y.M., Menon, J., Shimizu, F. and Viale, A. (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient specific iPS cells. Nature, 461(7262): 402-406. [Crossref] [PubMed] [PMC]

116. Drawnel, F.M., Boccardo, S., Prummer, M., Delobel, F., Graff, A., Weber, M., Gerard, R., Thong, L.B., Bu, L., Jiang, X., Hoflack, J.C., Kiialainen, A., Jeworutzki, E., Aoyama, N., Carlson, C., Burcin, M., Gromo, G., Boehringer, M., Stahlberg, H., Hall, B.J., Magnone, M.C., Kolaja, K., Chien, K.R., Bailly, J. and Iacone, R. (2014) Disease modelling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent. Stem Cell Rep., 9: 810-820. [PubMed]

117. Xu, X.H. and Zhong, Z. (2013) Disease modelling and drug screening for neurological diseases using human induced pluripotent stem cells. Acta Pharmacol. Sin., 34: 755-764. [Crossref] [PubMed] [PMC]

118. Egawa, N., Kitaoka, S., Tsukita, K., Naitoh, M., Takahashi, K., Yamamoto, T., Adachi, F., Kondo, T., Okita, K., Asaka, I., Aoi, T., Watanabe, A., Yamada. Y., Morizane, A., Takahashi, J., Ayaki, T., Ito, H., Yoshikawa, K., Yamawaki, S., Suzuki, S., Watanabe, D., Hioki, D., Kaneko, T., Makioka, K., Okamoto, K., Takuma, H., Tamaoka, A., Hasegawa, K., Nonaka, T., Hasegawa, M., Kawata, A., Yoshida, M., Nakahata, T., Takahashi, R., Marchetto, M.C., Gage, F.H., Yamanaka, S. and Inoue, H. (2012) Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci. Transl. Med., 4(145): 145. [Crossref]

119. Davidson, M.D., Ware, B.R. and Khetani, S.R. (2015) Stem cell-derived liver cells for drug testing and disease modelling. Discov. Med., 19(106): 349-358. [PubMed]

120. Zhu, Y., Hu, L. and Li, P. (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. [Crossref] [PubMed] [PMC]

121. Yang, S., Bo, J. and Hu, H. (2012) Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules. Cell Prolif., 45(2): 91-100. [Crossref] [PubMed]

122. Li, P., Hu, H. and Yang, S. (2013) Differentiation of induced pluripotent stem cells into male germ cells in vitro through embryoid body formation and retinoic acid or testosterone induction. Bio Med. Res. Int. 2013: 608728. [PubMed]

123. Malik, N. and Rao, M.S. (2013) A review of the methods for human iPSC derivation. Methods Mol. Biol., 997: 23-33. [Crossref] [PubMed] [PMC]

124. Xu, X., Yi, F.Z. and Pan, H. (2013) Progress and prospects in stem cell therapy. Acta Pharmacol. Sin., 34(6): 741-746. [Crossref] [PubMed] [PMC]

125. Hayashi, K., Ohta, H., Kurimoto, K., Aramaki, S. and Saitou, M. (2011) Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell, 146(4): 519-532. [Crossref] [PubMed]

126. Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T. and Saitou, M. (2009) A signaling principle for the specification of the germ cell lineage in mice. Cell, 137(3): 571-584. [Crossref] [PubMed]

127. Volarevic, V., Bojic, S., Nurkovic, J., Volarevic, A., Ljujic, B., Arsenijevic, N., Lako, M. and Stojkovic, M. (2014) Stem cells as new agents for the treatment of infertility: Current and future perspectives and challenges. Bio Med. Res. Int., 2014: 507234-507238. [Crossref] [PubMed] [PMC]

128. Brevini, T.A., Antonini, S., Cillo, F., Crestan, M. and Gandolfi, F. (2007) Porcine embryonic stem cells: Facts, challenges and hopes. Theriogenology, 68: 206-213. [Crossref] [PubMed]

129. Nagy, K., Sung, H.K., Zhang, P., Laflamme, S., Vincent, P. and Mohammadi, S. (2011) Induced pluripotent stem cell lines derived from equine fibroblasts. Stem Cell Rev., 7: 693-702. [Crossref] [PubMed] [PMC]

130. Fan, N., Chen, J., Shang, Z., Dou, H., Ji, G. and Zou, Q. (2013) Piglets cloned from induced pluripotent stem cells. Cell Res., 23: 162-166. [Crossref] [PubMed] [PMC]

131. West, F.D., Terlouw, S.L., Kwon, D.J., Mumaw, J.L., Dhara, S.K., Hasneen, K., Dobrinsky, J.R. and Stice, S.L. (2010) Porcine induced pluripotent stem cells produce chimeric off springs. Stem Cells Dev., 19(8): 1211-1220. [Crossref] [PubMed]

132. Baker, M. (2009) iPS cells make mice that make mice. Nat. Rep. Stem Cells. [Crossref]

133. Guo, J., Baojiang, W., Shuyu, L., Siqin, B., Lixia, Z., Shuxiang, H., Wei, S., Jie, S., Yangfeng, D. and Xihe, L. (2014) Contribution of mouse embryonic stem cells and induced pluripotent stem cells to chimeras through injection and co-culture of embryos. Stem Cell Int., 2014: Article ID: 409021, 1-9.