Abstract
Rats make an excellent model system for studying xenotransplantation since, like mice pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent stem cells as well as gene knock-outs are also available for rats, besides rats have larger organs. The emergence of new genome-editing tools combined with stem cell technology, has revolutionized biomedical research including the field of regenerative medicine. The aim of this manuscript is to provide an overview of the recent progresses in stem cell-derived organ regeneration involving “gene knock-out” and “blastocyst complementation” in the rat model system. Knocking-out Pdx1, Foxn1, and Sall1 genes have successfully generated rat models lacking the pancreas, thymus, and kidney, respectively. When allogeneic (rat) or xenogeneic (mouse) pluripotent stem cells were microinjected into blastocyst-stage rat embryos that had been designed to carry a suitable organogenetic niche, devoid of specific organs, the complemented blastocysts were able to develop to full-term chimeric rat offspring containing stem cell-derived functional organs in their respective niches. Thus, organs with a tridimensional structure can be generated with pluripotent stem cells in vivo, accelerating regenerative medical research, which is crucial for organ-based transplantation therapies. However, to address ethical concerns, public consent after informed discussions is essential before production of human organs within domestic animals.
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Acknowledgements
Dr. Toshihiro Kobayashi (National Institute for Physiological Sciences, Aichi, Japan) is appreciated for his valuable comments on this manuscript. Our research was supported by Grants-in-Aids for Scientific Research from Japan Society for the Promotion of Science (JSPS; 25290037 to MH and 16K07985 to SH), Exploratory Research for Advanced Technology, Nakauchi Stem Cell and Organ Regeneration Project from Japan Science and Technology Agency (ERATO-JST; to MH), and Leading Advanced Projects for medical innovation from Japan Agency for Medical Research and Development (LEAP-AMED; JP18gm0010002 to MH).
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Hirabayashi, M., Goto, T. & Hochi, S. Pluripotent stem cell-derived organogenesis in the rat model system. Transgenic Res 28, 287–297 (2019). https://doi.org/10.1007/s11248-019-00161-2
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DOI: https://doi.org/10.1007/s11248-019-00161-2