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Induced pluripotent stem cells – alchemist's tale or clinical reality?

Published online by Cambridge University Press:  13 August 2010

S. Tamir Rashid  and
Ludovic Vallier
S. Tamir Rashid
Affiliation:
Laboratory for Regenerative Medicine, University of Cambridge, Cambridge, UK. Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, UK.
Ludovic Vallier*
Affiliation:
Laboratory for Regenerative Medicine, University of Cambridge, Cambridge, UK.
*
*Corresponding author: Ludovic Vallier, Laboratory for Regenerative Medicine, University of Cambridge, West Forvie Building, Robinson Way, Cambridge, CB2 0SZ, UK. E-mail: [email protected]
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Abstract

Following Shinya Yamanaka's first report describing the reprogramming of fibroblasts into stem cells over three years ago, some sceptics initially drew analogies between this new field of research and the quasi-mystical practice of ‘alchemy’. Unlike the alchemist, however, stem cell researchers have rigorously tested and repeated experiments, proving their very own brand of cellular ‘alchemy’ to be a reality, with potentially massive implications for the study of human biology and clinical medicine. These investigations have resulted in an explosion of related publications and initiated the field of stem cell research known as ‘induced pluripotency’. In this review, we give an account of the historical development, current technologies and potential clinical applications of induced pluripotency and conclude with a perspective on the possible future directions for this dynamic field.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e25
Copyright
Copyright © Cambridge University Press 2010

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References

References

1Gurdon, J.B., Elsdale, T.R. and Fischberg, M. (1958) Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182, 64-65CrossRefGoogle ScholarPubMed
2Campbell, K.H.S. et al. (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380, 64-66CrossRefGoogle ScholarPubMed
3Cowan, C.A. et al. (2005) nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309, 1369-1373CrossRefGoogle ScholarPubMed
4Silva, J. et al. (2006) Nanog promotes transfer of pluripotency after cell fusion. Nature 441, 997-1001CrossRefGoogle ScholarPubMed
5Takahashi, K. and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676CrossRefGoogle ScholarPubMed
6Okita, K., Ichisaka, T. and Yamanaka, S. (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317CrossRefGoogle ScholarPubMed
7Wernig, M. et al. (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318-324CrossRefGoogle ScholarPubMed
8Takahashi, K. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872CrossRefGoogle ScholarPubMed
9Yu, J. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920CrossRefGoogle ScholarPubMed
10Zhao, X.-Y. et al. (2009) iPS cells produce viable mice through tetraploid complementation. Nature 461, 86-90CrossRefGoogle ScholarPubMed
11Boland, M.J. et al. (2009) Adult mice generated from induced pluripotent stem cells. Nature 461, 91-94CrossRefGoogle ScholarPubMed
12Mikkelsen, T.S. et al. (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454, 49-55CrossRefGoogle ScholarPubMed
13Chin, M.H. et al. (2009) Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5, 111-123CrossRefGoogle ScholarPubMed
14Brons, I.G. et al. (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191-195CrossRefGoogle ScholarPubMed
15Vallier, L., Alexander, M. and Pedersen, R. (2007) Conditional gene expression in human embryonic stem cells. Stem Cells 25, 1490-1497CrossRefGoogle ScholarPubMed
16Vallier, L. et al. (2009) Signaling pathways controlling pluripotency and early cell fate decisions of human induced pluripotent stem cells. Stem Cells 27, 2655-2666CrossRefGoogle ScholarPubMed
17Sridharan, R. et al. (2009) Role of the murine reprogramming factors in the induction of pluripotency. Cell 136, 364-377CrossRefGoogle ScholarPubMed
18Banito, A. et al. (2009) Senescence impairs successful reprogramming to pluripotent stem cells. Genes and Development 23, 2134-2139CrossRefGoogle ScholarPubMed
19Hong, H. et al. (2009) Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460, 1132-1135CrossRefGoogle ScholarPubMed
20Krizhanovsky, V. and Lowe, S.W. (2009) Stem cells: The promises and perils of p53. Nature 460, 1085-1086CrossRefGoogle ScholarPubMed
21Ghosh, Z. et al. Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells. PLoS One 5, e8975CrossRefGoogle Scholar
22Park, I.H. (2008) Disease-specific induced pluripotent stem cells. Cell 134, 877-886CrossRefGoogle ScholarPubMed
23Dimos, J.T. (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218-1221CrossRefGoogle ScholarPubMed
24Soldner, F. et al. (2009) Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964-977CrossRefGoogle ScholarPubMed
25Karumbayaram, S. et al. (2009) directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells 27, 806-811CrossRefGoogle ScholarPubMed
26Zhang, J. et al. (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research 104, e30-41CrossRefGoogle ScholarPubMed
27Zhang, D. et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Research 19, 429-438CrossRefGoogle Scholar
28Taura, D. et al. (2009) Adipogenic differentiation of human induced pluripotent stem cells: Comparison with that of human embryonic stem cells. FEBS Letters 583, 1029-1033CrossRefGoogle ScholarPubMed
29Choi, K.-D. et al. (2009) Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells 27, 559-567CrossRefGoogle ScholarPubMed
30Taura, D. et al. (2009) Induction and isolation of vascular cells from human induced pluripotent stem cells–Brief Report. Arteriosclerosis, Thrombosis and Vascular Biology 29, 1100-1103CrossRefGoogle ScholarPubMed
31Lamba, D.A. et al. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS One 5, e8763CrossRefGoogle Scholar
32Touboul, T. et al. Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51, 1754-1765CrossRefGoogle Scholar
33Si-Tayeb, K. et al. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51, 297-305CrossRefGoogle Scholar
34Sullivan, G.J. et al. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51, 329-335CrossRefGoogle Scholar
35Gallicano, G.I. and Mishra, L.Hepatocytes from induced pluripotent stem cells: A giant leap forward for hepatology. Hepatology 51, 20-22CrossRefGoogle Scholar
36Ebert, A.D. et al. (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277-280CrossRefGoogle ScholarPubMed
37Lee, G. et al. (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402-406CrossRefGoogle ScholarPubMed
38Zhang, Y.W., Denham, J. and Thies, R.S. (2006) Oligodendrocyte Progenitor Cells Derived from Human Embryonic Stem Cells Express Neurotrophic Factors. Stem Cells and Development 15, 943-952CrossRefGoogle ScholarPubMed
39Nelson, T.J. et al. (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120, 408-416CrossRefGoogle ScholarPubMed
40Wernig, M. et al. (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 105, 5856-5861CrossRefGoogle ScholarPubMed
41Hanna, J. et al. (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318, 1920-1923CrossRefGoogle ScholarPubMed
42Xu, D. et al. (2009) Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proceedings of the National Academy of Sciences of the United States of America 106, 808-813CrossRefGoogle ScholarPubMed
43Raya, A. et al. (2009) Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460, 53-59CrossRefGoogle ScholarPubMed
44Maherali, N. (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55-70CrossRefGoogle ScholarPubMed
45Aoi, T. et al. (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321, 699-702CrossRefGoogle ScholarPubMed
46Stadtfeld, M. et al. (2008) Induced pluripotent stem cells generated without viral integration. Science 322, 945-949CrossRefGoogle ScholarPubMed
47Kim, J.B. et al. (2009) Oct4-Induced Pluripotency in Adult Neural Stem Cells. Cell 136, 411-419CrossRefGoogle ScholarPubMed
48Hanna, J. et al. (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133, 250-264CrossRefGoogle ScholarPubMed
49Aasen, T. et al. (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology 26, 1276-1284CrossRefGoogle ScholarPubMed
50Kim, J.B. et al. (2009) Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649-643CrossRefGoogle ScholarPubMed
51Loh, Y.-H. et al. (2009) Generation of induced pluripotent stem cells from human blood. Blood 113, 5476-5479CrossRefGoogle ScholarPubMed
52Giorgetti, A. et al. (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5, 353-357CrossRefGoogle ScholarPubMed
53Haase, A. et al. (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5, 434-441CrossRefGoogle ScholarPubMed
54Miura, K. et al. (2009) Variation in the safety of induced pluripotent stem cell lines. Nature Biotechnology 27, 743-745CrossRefGoogle ScholarPubMed
55Hanna, J. et al. (2009) Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595-601CrossRefGoogle ScholarPubMed
56Hacein-Bey-Abina, S. (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. The Journal of Clinical Investigation 118, 3132-3142CrossRefGoogle ScholarPubMed
57Maherali, N. et al. (2008) A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3, 340-345CrossRefGoogle ScholarPubMed
58Zhou, W. and Freed, C.R. (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27, 2667-2674CrossRefGoogle ScholarPubMed
59Okita, K. et al. (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949-953CrossRefGoogle ScholarPubMed
60Yu, J. et al. (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797-801CrossRefGoogle ScholarPubMed
61Kaji, K. et al. (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458, 771-775CrossRefGoogle ScholarPubMed
62Woltjen, K. et al. (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766-770CrossRefGoogle ScholarPubMed
63Yusa, K. et al. (2009) Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nature Methods 6, 363-369CrossRefGoogle ScholarPubMed
64Wang, W. (2008) Chromosomal transposition of PiggyBac in mouse embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 105, 9290-9295CrossRefGoogle ScholarPubMed
65Fusaki, N. et al. (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. Proceedings of the Japan Academy, Series B 85, 348-362CrossRefGoogle Scholar
66Huangfu, D. (2008) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnology 26, 795-797CrossRefGoogle ScholarPubMed
67Shi, Y. et al. (2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568-574CrossRefGoogle ScholarPubMed
68Shi, Y. et al. (2008) A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525-528CrossRefGoogle ScholarPubMed
69Ichida, J.K. et al. (2009) A small-molecule inhibitor of Tgf-[beta] signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell 5, 491-503CrossRefGoogle ScholarPubMed
70Mali, P. et al. Butyrate Greatly Enhances Derivation of Human Induced Pluripotent Stem Cells by Promoting Epigenetic Remodeling and the Expression of Pluripotency-Associated Genes. Stem Cells 28, 713-720CrossRefGoogle Scholar
71Lin, T. et al. (2009) A chemical platform for improved induction of human iPSCs. Nature Methods 6, 805-808CrossRefGoogle ScholarPubMed
72Zhou, H. et al. (2009) Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins. Cell Stem Cell 4, 381-384CrossRefGoogle ScholarPubMed
73Kim, D. et al. (2009) Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins. Cell Stem Cell 4, 472-476CrossRefGoogle ScholarPubMed
74Hu, B.-Y. et al. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences 107, 4335-4340CrossRefGoogle Scholar
75Zhou, Q. et al. (2008) In vivo reprogramming of adult pancreatic exocrine cells to [bgr]-cells. Nature 455, 627-632CrossRefGoogle Scholar
76Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035-1041CrossRefGoogle Scholar
77Aasen, T. (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology 26, 1276-1284CrossRefGoogle ScholarPubMed
78Touboul, T. et al. (2010) Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions which recapitulate liver development. Hepatology 51, 1754-1765CrossRefGoogle ScholarPubMed
79Kim, J.B. (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454, 646-650CrossRefGoogle ScholarPubMed
80Sun, N. et al. (2009) Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proceedings of the National Academy of Sciences 106, 15720-15725CrossRefGoogle ScholarPubMed
81Taura, D. et al. (2009) Induction and isolation of vascular cells from human-induced pluripotent stem cells. Arteriosclerosis, Thrombosis and Vascular Biology 29, 1100-1103CrossRefGoogle ScholarPubMed

Further reading resources and contacts

International society for stem cell research:

Saha, K. and Jaenisch, R. (2009) Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell 5, 584-595CrossRefGoogle ScholarPubMed
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