Establishment of embryonic stem cells from rat blastocysts

Rats have important advantages over mice as an experimental system for physiological and pharmacological investigations. Their embryonic stem (ES) cells, after differentiation into each tissue or organ, are applied in regenerative medicine, which enables examination of the effects of drugs for various diseases. Knockout rats will also provide a suitable model system for many human diseases and a great amount of new insights into gene functions, which have not been revealed by knockout mice. In 2008, we experienced the world's first success in establishing rat ES cells with chimeric contribution. Following on the heels of our report, others reported the establishment of rat ES cells that could complete a germline transmission. Recent studies on rat as well as mouse ES cells suggest that modifications of signal inhibitors and serum in the medium are critical for the maintenance of the pluripotency of ES cells. In this chapter, we discuss techniques for the successful establishment and maintenance of rat ES cells.