Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in rats
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REVIEW ARTICLE
Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in rats Masumi Hirabayashi • Shinichi Hochi
Received: 20 April 2011 / Accepted: 3 June 2011 / Published online: 24 June 2011 Ó Japan Society for Reproductive Medicine 2011
Abstract Over the past 25 years, the reverse genetic approach including precise and conditional replacement or loss of gene function at a specific locus was considered possible only in mice due to the absence of embryonic stem (ES) or induced pluripotent stem (iPS) cell lines in other species. Recently, however, stem cell technology in rats has become available for biomedical research. In this paper we overview the recent progress of rat ES and iPS cell technology. Starting from the establishment of rat ES cells, the use of ES cells for foreign gene transfer and endogenous gene knock-out is discussed, followed by the successful establishment of rat iPS cells and the generation of an iPS cell-derived organ via interspecific blastocyst complementation. Finally, the possible contribution of rat stem cell technology to reproductive medicine is described. Keywords Embryonic stem cells Gene knock-out Organ regeneration Pluripotent stem cells Xenotransplantation
pharmacology and toxicology. There are more than 100 rat strains with various genetic backgrounds, including some useful models for human diseases (e.g., SHR and BB for hypertension and diabetes, respectively), as well as the uncountable number of transgenic rat strains. Rats have the advantage of being a reasonably well-characterized and intermediate-sized rodent that can be maintained more cheaply than larger animals and can often be manipulated more easily than smaller rodents. Although several technologies have been applied to modify rat genomes [1–3], the reverse genetic approach (precise and conditional replacements [knock-in] or loss of gene function [knock-out] at a specific locus) was considered impossible in rats because any protocols to establish stem cell lines conventionally used in mice [4, 5] were not applicable to rats. Recently, however, functional germlinecompetent embryonic stem (ES) cell lines [6, 7] and induced pluripotent stem (iPS) cell lines [8, 9] have been reported for this species. General advantages and disadvantages of ES and iPS cells are summarized in Table 1. In this paper we discuss the recent progress of rat ES/iPS cell technology.
Introduction Rats (Rattus norvegicus) have been used more extensively than mice in the research fields of neuroscience,
Embryonic stem cells Establishment of ES cells from blastocysts
M. Hirabayashi (&) Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Higashiyama 4-1, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan e-mail: [email protected] S. Hochi Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano, Japan
The breakthrough in establishing rat ES cell lines was at the end of 2008. Functional germline-competent ES cell lines were reported by using a fe
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