Jun Takahashi
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氏名Name
Jun Takahashi
所属・職名Affiliation, Title, etc.
Center for iPS Cell Research and Application, Kyoto University, Director/Professor
研究室HPWebsite
一言メッセージShort Message
Create the Brain
本プロジェクトでの研究概要Outline of the research in this project
Cognitive function is known to be impaired by damage to the thalamus or prefrontal cortex. In this study, we will establish a rat model of cognitive dysfunction by inducing photocoagulation in these regions using Rose Bengal. We induce cerebral cortical and thalamic organoids—self-organized cellular aggregates with specific structures— from human induced pluripotent stem (iPS) cells. The differentiated neurons will then be transplanted around the infarcted areas. Following transplantation, cognitive function will be assessed using maze tests, and histopathological analyses will be conducted to evaluate axonal elongation and neuronal circuit reconstruction from the transplanted cells.
これまで主な研究内容Outline of main research so far
Our laboratory is dedicated to developing cell transplantation therapies using iPS cells for intractable neurological diseases, with a particular focus on restoring neural circuits to improve functional outcomes. Our primary target diseases are Parkinson’s disease and cerebral infarction. To assess the safety and efficacy of transplanted cells, we have conducted behavioral and imaging analyses using mouse, rat, and crab-eating monkey models of Parkinson’s disease. Additionally, we have thoroughly evaluated the safety and efficacy of dopaminergic neurons intended for clinical application. Based on these findings, we obtained regulatory approval and initiated an investigator-led clinical trial for Parkinson’s disease at Kyoto University Hospital in 2018, which was successfully completed in 2023. In addition, we are now working toward developing a cell transplantation therapy for cerebral infarction. To this end, we are engaged in the induction of brain organoids from human iPS cells and conducting transplantation experiments using brain infarction model mice and rats.
主な経歴・受賞歴等Career, Awards, etc.
＜Short Biography＞
Jun Takahashi is the Director and Professor at the Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan. He graduated from the Kyoto University Faculty of Medicine in 1986 and began his career as a neurosurgeon at Kyoto University Hospital. After earning his Ph.D. from the Kyoto University Graduate School of Medicine, he pursued postdoctoral research at the Salk Institute in California, USA, under the mentorship of Dr. Fred Gage, where he initiated his research on neural stem cells. Upon returning to Kyoto University, he became a full professor at CiRA in 2012, focusing on the development of iPS cell-based therapies. As a physician-scientist, he has played a pioneering role in translating iPS cell research into clinical applications and led the world’s first clinical trial for Parkinson’s disease using iPS cells from 2018 to 2021.
＜Awards＞
- 2005
- Cell Replacement Therapy for Parkinson's Disease Award by The Michael J. Fox Foundation
for Parkinson's Research - 2018
- Japanese Society for Regenerative Medicine Award
主要業績Major Publications
Sawamoto N, Doi D, Nakanishi E, Sawamura M, Kikuchi T, Yamakado H, Taruno Y, Shima A, Fushimi Y, Okada T, Kikuchi T, Morizane A, Hiramatsu S, Anazawa T, Shindo T, Ueno K, Morita S, Arakawa Y, Nakamoto Y, Miyamoto S, Takahashi Ryosuke and Takahashi J. Phase I/II trial of iPSC-derived dopaminergic cells for Parkinson's disease. Nature (2025) in press.
Ikeda M, Doi D, Ebise H, Ozaki Y, Fujii M, Kikuchi T, Yoshida K, Takahashi J. Validation of non-destructive morphology-based selection of cerebral cortical organoids by paired morphological and single-cell RNA-seq analyses. Stem Cell Rep. 19(11): 1635-1646 (2024)
https://doi.org/10.1016/j.stemcr.2024.09.005
Yamagami K, Samata B, Doi D, Tsuchimochi R, Kikuchi T, Amimoto N, Ikeda M, Yoshimoto K, Takahashi J. Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons. Stem Cells Transl Med. 13: 1113-1128 (2024)
https://doi.org/10.1093/stcltm/szae066
Tsuchimochi R, Yamagami K, Kubo N, Amimoto N, Raudzus F, Samata B, Kikuchi T, Doi D, Yoshimoto K, Mihara A, Takahashi J. Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain. Stem Cell Rep. 18(4):899-914 (2023) doi: 10.1016/j.stemcr.2023.02.012.
Kitahara T, Sakaguchi H, Morizane A, Kikuchi T, Miyamoto S, Takahashi J. Axonal extensions along corticospinal tracts from transplanted human cerebral organoids. Stem Cell Rep. 15(2): 467-481 (2020). doi: 10.1016/j.stemcr.2020.06.016
Doi D, Magotani H, Kikuchi T, Ikeda M, Hiramatsu S, Yoshida K, Amano N, Nomura M, Umekage M, Morizane A, Takahashi J. Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease. Nat Commun 11: 3369 (2020). doi: 10.1038/s41467-020-17165-w
Sakaguchi H, Ozaki Y, Ashida T, Matsubara T, Oishi N, Kihara S, Takahashi J. Self-organized synchronous calcium transients in a cultured human neural network derived from cerebral organoids. Stem Cell Rep. 13(3): 458-473 (2019)
Morizane A, Kikuchi T, Hayashi T, Mizuma H, Takara S, Doi H, Mawatari A, Glasser M F, Shiina T, Ishigaki H, Itoh Y, Okita K, Yamasaki E, Doi D, Onoe H, Ogasawara K, Yamanaka S, Takahashi J. MHC matching improves engraftment of iPSC-derived neurons in non-human primates. Nat Commun. 8:385 (2017)
Kikuchi T, Morizane A, Doi D, Magotani H, Onoe H, Hayashi T, Mizuma H, Takara S, Takahashi R, Inoue H, Morita S, Yamamoto M, Okita K, Nakagawa M, Parmar M, Takahashi J. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 548: 592-96 (2017)
Doi D, Samata B, Katsukawa M, Kikuchi T, Morizane A, Ono Y, Sekiguchi K, Nakagawa M, Parmar M, Takahashi J. Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation. Stem Cell Reports. 2(3): 337-350 (2014).
