GENERATION OF FUNCTIONAL HUMAN ORGAN FROM PLURIPOTENT STEM CELL Hideki Taniguchi, M.D., Ph.D. and Takanori Takebe, M.D. Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, JAPAN ABSTRACT Organ transplantation is the only curative method for treating end-stage organ failure. Over the past decade, there has been increased demand for organ transplantation throughout the world owing to the increased incidence of organ failure. To address such important clinical issue, a critical shortage of donor organs highlights the urgent need for generating organs from human pluripotent stem cells. Here we show the generation of functional human organ from human induced pluripotent stem cells (iPSCs) by transplantation of organ buds created in vitro. Human vasculatures in iPSC-organ bud transplants became functional by connecting to the recipient’s vessels. The formation of functional vasculatures stimulated the maturation of iPSC-organ bud into tissue resembling the adult organ. This method is the alternative way to the generation of functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of- concept demonstration of organ-bud transplantation provides a promising new approach to a critical shortage of donor organs for treating end-stage organ failure. KEYWORDS: Organ transplantation INTRODUCTION Please refer to the abstract. THEORY In the organogenesis process, co-operative interaction is caused by multi-cellular system taking organized tissue structure, and the true functional cells, which finally accomplished terminal differentiation while being accompanied by the change of the interval in dynamic space and time, are brought about. The conventional way of thinking to which a cell of the purpose is led is reconsidered radically to achieve creation of a function cell, and it is necessary to establish a terminal differentiation derivative method with the reconstitution of the three-dimensional high-level structure that imitated in vivo organogenesis. EXPERIMENTAL Please refer to the references(1-3). 978-0-9798064-8-3/µTAS 2015/$20©15CBMS-0001 332 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA RESULT AND DISCUSSION Please refer to the references(1-3). CONCLUSION Proof-of-concept organ bud transplantation might be a rational approach toward the generation of vascularized and functional complex organs. This culture principle will not only be a powerful tool for the study of human developmental biology and pathol- ogy using pluripotent stem cells, but it will also facilitate the realization of next-generation generative medicine using in-vitro-grown complex tissue architectures for currently un- treatable patients. ACKNOWLEDGEMENTS This work was supported by grants to H. Taniguchi from the Strategic Promotion of Innovative Research and Development (S-innovation, 62890004) of the Japan Science and Technology Agency (JST). This work was also supported by the Grants-in-Aid of the Ministry of Education, Culture, Sports, Science, and Technology of Japan. This work was also partly supported by the JST through its research grant Research Center Network for Realization of Regenerative Medicine. T. Takebe and H.T. have served on scientific advisory boards for Healios Inc. T. Takebe and H.T. have also granted a license to Healios through Yokohama City University over their inventions that relate to the subject of this manuscript. T.Takebe and H.T. are conducting research under the collaborative research agreement with Healios and the subject of the research also relates to the subject of this manuscript. REFERENCES 1. Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, Matsuzaki T, Yamazaki T, Toyohara T, Osafune K, Nakauchi H, Yoshikawa HY, Taniguchi H : Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. Cell Stem Cell 16: 556-565, 2015 2. Takebe T, Zhang RR, Koike H, Kimura M, Yoshizawa E, Enomura M, Koike N, Sekine K, Taniguchi H :Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature Protocols 9:396-409, 2014 3. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguch H :Vascularized and functional human liver tissue from an induced pluripotent stem cell-derived organ bud transplant. Nature 499:481-484,2013 CONTACT Hideki Taniguchi; phone:+81-45-787-2621; [email protected] 333
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