All Roads Lead to Induced Pluripotent Stem Cells: The Technologies of iPSC Generation
Open accessAbstract
Generation of induced pluripotent stem cells (iPSCs) via the ectopic expression of reprogramming factors is a simple, advanced, yet often perplexing technology due to low efficiency, slow kinetics, and the use of numerous distinct systems for factor delivery. Scientists have used almost all available approaches for the delivery of reprogramming factors. Even the well-established retroviral vectors confuse some scientists due to different tropisms in use. The canonical virus-based reprogramming poses many problems, including insertional mutagenesis, residual expression and re-activation of reprogramming factors, uncontrolled silencing of transgenes, apoptosis, cell senescence, and strong immunogenicity. To eliminate or alleviate these problems, scientists have tried various other approaches for factor delivery and transgene removal. These include transient transfection, nonintegrating viral vectors, Cre-loxP excision of transgenes, excisable transposon, protein transduction, RNA transfection, microRNA transfection, RNA virion, RNA replicon, nonintegrating replicating episomal plasmids, minicircles, polycistron, and preintegration of inducible reprogramming factors. These alternative approaches have their own limitations. Even iPSCs generated with RNA approaches should be screened for possible transgene insertions mediated by active endogenous retroviruses in the human genome. Even experienced researchers may encounter difficulty in selecting and using these different technologies. This survey presents overviews of iPSC technologies with the intention to provide a quick yet comprehensive reference for both new and experienced reprogrammers.
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All non-integrating methods for iPSC generation have low reprogramming efficiency except the Sendai viral vector.
“However, all of these methods have low re-programming efficiency, except the Sendai viral vector [100].”
From Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through (2022) · cites this paper as [100]
Cites
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) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.012 · Cited by 2,662 · see citing works
Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse
Stadtfeld, M., Maherali, N., Breault, D. T., & Hochedlinger, K. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.02.001 · Cited by 823 · see citing works
A nonviral minicircle vector for deriving human iPS cells
Jia, F., Wilson, K. D., Sun, N., Gupta, D. M., Huang, M., Li, Z., Panetta, N. J., Chen, Z. Y., Robbins, R. C., Kay, M. A., et al. (2010) · Nature Methods · doi:10.1038/nmeth.1426 · Cited by 734 · see citing works
Induced Pluripotent Stem Cell Generation Using a Single Lentiviral Stem Cell Cassette
Sommer, C. A., Stadtfeld, M., Murphy, G. J., Hochedlinger, K., Kotton, D. N., & Mostoslavsky, G. (2009) · Stem Cells · doi:10.1634/stemcells.2008-1075 · Cited by 676 · see citing works
A High-Efficiency System for the Generation and Study of Human Induced Pluripotent Stem Cells
Maherali, N., Ahfeldt, T., Rigamonti, A., Utikal, J., Cowan, C., & Hochedlinger, K. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.08.003 · Cited by 563 · cited 4× · see citing works
“Kinetics of human reprogramming was examined using such secondary inducible reprogramming by timed withdrawal of the inducer (doxycycline) [64,130].”
BackgroundMethodInfluentialAdenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells
Zhou, W., & Freed, C. R. (2009) · Stem Cells · doi:10.1002/stem.201 · Cited by 538 · see citing works
Efficient generation of human iPSCs by a synthetic self-replicative RNA
Yoshioka, N., Gros, E., Li, H.-R., Kumar, S., Deacon, D. C., Maron, C., Muotri, A. R., Chi, N. C., Fu, X.-D., Yu, B. D., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.06.001 · Cited by 312 · see citing works
Papapetrou, E. P., Tomishima, M. J., Chambers, S. M., Mica, Y., Reed, E., Menon, J., Tabar, V., Mo, Q., Studer, L., & Sadelain, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904825106 · Cited by 286 · see citing works
Efficient gene transfer to airway epithelium using recombinant Sendai virus
Yonemitsu, Y., Kitson, C., Ferrari, S., Farley, R., Griesenbach, U., Judd, D., Steel, R., Scheid, P., Zhu, J., Jeffery, P. K., et al. (2000) · Nature Biotechnology · doi:10.1038/79463 · Cited by 244 · see citing works
Generation of adult human induced pluripotent stem cells using nonviral minicircle DNA vectors
Narsinh, K. H., Jia, F., Robbins, R. C., Kay, M. A., Longaker, M. T., & Wu, J. C. (2011) · Nature Protocols · doi:10.1038/nprot.2010.173 · Cited by 214 · see citing works
Feeder-Free Derivation of Human Induced Pluripotent Stem Cells with Messenger RNA
Warren, L., Ni, Y., Wang, J., & Guo, X. (2012) · Scientific Reports · doi:10.1038/srep00657 · Cited by 154 · see citing works
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Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through
Gurumoorthy, N., Nordin, F., Tye, G. J., Wan Kamarul Zaman, W. S., & Ng, M. H. (2022) · Biomedicines · doi:10.3390/biomedicines10010107 · Cited by 69 · see citing works
Yoshioka, N., & Dowdy, S. F. (2017) · PLOS ONE · doi:10.1371/journal.pone.0182018 · Cited by 36 · see citing works
- Authors
- Hu, K.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Hu, Kejin
- ORCID
- Hu, Kejin
- Venue
- Stem Cells and Development
- Publisher
- SAGE Publications
- Published
- 2014-02-13
- Volume
- 23
- Issue
- 12
- Pages
- 1285-1300
- ISSN
- 1525-8165 (ISSN-L)
- 1547-3287
- 1557-8534
- PMC
- PMC4046204
- OpenAlex
- W2109344960
- Cited by
- 105
- References
- 11
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 5 · 2018: 3 · 2017: 12 · 2016: 17 · 2015: 13 · 2014: 5 · 2013: 1
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Stem Cells and Development (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- induced pluripotent stem cells, reprogramming factors, reprogramming efficiency, retroviral vectors, insertional mutagenesis, transgene silencing, transient transfection, protein transduction, RNA transfection, microRNA transfection, RNA replicon, episomal plasmids, minicircles, endogenous retroviruses
- MeSH terms
- Cell Differentiation, Genetic Vectors, Humans, Transfection, Gene Expression Regulation, Developmental, Cell Culture Techniques, Induced Pluripotent Stem Cells, Cellular Reprogramming
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