Human induced pluripotent stem cell (iPSC) technology has evolved rapidly since its inception in 2007.
Human iPSC technology has been widely used for disease modelling; for example, for neurodegenerative and psychiatric disorders.
Human iPSC technology has yielded several drug candidates that are currently in clinical trials.
The first clinical trial using human iPSC-derived products has been initiated for age-related macular degeneration.
The combination with gene editing and 3D organoid technologies makes the iPSC platform more powerful.
The continued development of iPSC technology and its integration with other technologies has the potential to make substantial contributions to disease modelling, drug discovery and regenerative medicine.
Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modelling, drug discovery and cell therapy development. Novel pathological mechanisms have been elucidated, new drugs originating from iPSC screens are in the pipeline and the first clinical trial using human iPSC-derived products has been initiated. In particular, the combination of human iPSC technology with recent developments in gene editing and 3D organoids makes iPSC-based platforms even more powerful in each area of their application, including precision medicine. In this Review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in the field.
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The authors thank the following individuals: J. Chao, L. Li, Q. Qu and E. Tian for their help in preparing the figures; P. Karagiannis and C. Gandhi for critically reading and editing the manuscript; and R. Carrasco, L. Zaragoza, A. M. Chrisney, M. Kong, Y. Miyake, N. Endo, R. Ueno and R. Okuyama for their administrative support. The work was partially funded by the following agencies and grants: the Herbert Horvitz Fellowship (to Y.S.); the Sidell Kagan Foundation (to Y.S.); the California Institute for Regenerative Medicine grants RB4-06277 (to Y.S.), TRAN1-08525 (to Y.S.), RT3-07798 (to J.C.W.) and DR2A-05394 (to J.C.W.); US National Institutes of Health grants R01 HL130020 (J.C.W.) and R01 HL128170 (J.C.W.); the iPS Cell Research Fund (to S.Y.); the Center for iPSC production, the Program for Intractable Diseases Research utilizing Disease-specific iPS cells, Research Center Network for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED) (to S.Y.); the grant for Core Center for iPS cell Research of Research Center Network for Realization of Regenerative Medicine from AMED (to S.Y., H.I.); the Program for Intractable Diseases Research utilizing disease-specific iPS cells from AMED (to H.I.); Research Project for Practical Applications of Regenerative Medicine from AMED (to H.I); the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to H.I.); and the Daiichi Sankyo Foundation of Life Science (to H.I.).
J.C.W. is a co-founder of Stem Cell Theranostics. S.Y. is a non-salaried scientific adviser of iPS Academia Japan. The other authors declare no competing interests.
- Embryonic stem cells
(ESCs). Pluripotent stem cells that are derived from the inner cell mass of human embryos.
- Induced pluripotent stem cells
(iPSCs). Pluripotent stem cells that are reprogrammed from somatic cells by introducing pluripotency factors.
- Regenerative medicine
A therapeutic approach in which damaged tissues or organs are replaced by stimulating self-repair or using in vitro-cultured tissues or organs derived from cells, presumably stem cells, of a patient or a donor.
- Gene editing
Genetic engineering in which DNA is modified by engineered nucleases. A relevant example is to make isogenic induced pluripotent stem cell lines using gene editing.
- CRIPSR–Cas9 technology
A highly popular gene editing tool based on a bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) nuclease from Streptococcus pyogenes. This technology has gained wide usage in gene editing because of its simplicity in design and ease of use.
- Precision medicine
A model that aims to offer medical treatment tailored to individual patients.
- Whole genome sequencing
(WGS). A high-throughput sequencing technology that uncovers the entire DNA sequence of a genome.
- Exome sequencing
A technology that determines the sequence of all expressed genes in a genome. It is also called whole exome sequencing (WES).
- Targeted deep sequencing
An approach that determines the sequence at regions of interest using next-generation sequencing technology.
- Direct conversion
A technology that enables one type of somatic cell to be reprogrammed into another type of somatic cell.
In vitro cultured 3D organ buds that resemble the cellular organization and structure of human organs, but are more primitive and at a smaller scale than endogenous organs.
- Good manufacturing practice
A system that guarantees products are manufactured by following specific guidelines recommended by regulatory agencies, such as the US Food and Drug Administration. Such compliance is mandatory for all pharmaceutical manufacturing.
Of the same individual.
Of genetically different individuals from the same species.
- MicroRNA switch
A biotechnology that turns a gene on or off depending on the microRNA (or microRNAs) inside the cell.
- Disease repositioning
Redefinition of a disease based on disease induced pluripotent stem cell-based phenotypes to identify common and new therapeutic approaches across diseases.
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Shi, Y., Inoue, H., Wu, J. et al. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16, 115–130 (2017). https://doi.org/10.1038/nrd.2016.245
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