1: iPS Cell-Derived Neural Stem/Progenitor Cell Transplantation for Subacute Spinal Cord Injury: World's First Clinical Study Supports Long-Term Safety

Nature Medicine.    

2026 Jul 21. doi: 10.1038/s41591-026-04549-6.

Keiko Sugai, Osahiko Tsuji, Kanehiro Fujiyoshi, Masahiro Ozaki, Takayuki Abe, Tsuneo Kohzuki, Hiroki Okawara, Tomonori Sawada, Miho Sumida, Ema Yoshioka, Tomoko Shofuda, Shioko Kawashima, Ryo Yamaguchi, Munehisa Shinozaki, Naoko Takasu, Narihito Nagoshi, Toshiki Okubo, Jun Kohyama, Takeshi Maeda, Yoshiyuki Yato, Yonehiro Kanemura, Shinya Yamanaka, Masaya Nakamura & Hideyuki Okano

This achievement was published in Nature Medicine in July 2026, with Keiko Sugai and Nagahisa Tsuji of the Department of Orthopedic Surgery, School of Medicine as first authors, and Professor Masaya Nakamura (Orthopedic Surgery) and Professor Hideyuki Okano (Keio University Regenerative Medicine Research Center (KRM)) as corresponding authors. For spinal cord injuries, a treatment method to regenerate damaged neural circuits has not yet been established. In this study, Keio University Hospital and Murayama Medical Center collaborated to conduct the world's first clinical study in which human iPS cell-derived neural stem/progenitor cells (iPSC-NS/PCs) were transplanted into the damaged spinal cords of four patients with severe subacute spinal cord injury. Neural stem/progenitor cells have the ability to differentiate into neurons and glial cells. With safety as the primary endpoint, the four cases were followed for two to four years, and no tumor formation by the transplanted cells or serious adverse events were observed, supporting long-term safety. In exploratory evaluations, the extent of improvement in motor function and the rate of improvement in spinal cord injury severity up to 52 weeks post-transplantation exceeded the historical controls extracted from the database of the Japan Spinal Cord Foundation (Maeda, Sakai, Ideta, et al.). However, as this study was a single-arm trial of four cases, further verification is required regarding efficacy. This achievement is considered a step toward the practical application of spinal cord regenerative medicine using iPS cells.

(Keiko Sugai, Department of Orthopedic Surgery)

Nature Genetics.    

12 June 2026; 58: 1341–1352. doi.org/10.1038/s41588-026-02616-9

Masayuki Fujii, Naoko Abeto, Shotaro Kishimoto, Kouya Shiraishi, Taiki Hashimoto, Nobuyoshi Hiraoka, Satoru Nonaka, Motohiro Kojima, Mami Matano, Sirirat Takahashi, Gabriele Colozza, Bon-Kyoung Koo, Yasushi Yatabe, Motohiko Kato, Toshiro Sato & Shigeki Sekine

The so-called adenoma-carcinoma sequence, in which cancer develops from tubular adenomas as precursor lesions, is well known as the main carcinogenic pathway for colorectal cancer. Small bowel cancer is thought to develop through a similar pathway, but the frequency of APC gene mutations found in the majority of small bowel adenomas is less than 30% in small bowel cancer, suggesting that a significant number of cases develop from precursor lesions other than APC-mutated adenomas. In this study, we discovered that unlike the typical flat morphology of APC-mutated adenomas, some small bowel adenomas exhibit a distinct protruded macroscopic morphology, and that COPA gene mutations are found in approximately half of these protruded small bowel adenomas. The COPA protein constitutes part of the coatomer that coats retrograde vesicles between the Golgi apparatus and the endoplasmic reticulum, and it has rarely been linked to cancer. Verification using patient-derived organoids and gene-edited organoids revealed that COPA mutations enable growth even without the growth factor R-spondin, which is essential for Wnt signal activation. No previous reports have linked COPA to the Wnt pathway, and COPA gene mutations can be described as a new cancer driver that activates the Wnt pathway through a mechanism different from APC mutations. The results of this research are expected to lead to new classifications and diagnoses of small bowel tumors based on macroscopic findings and genetic mutations, as well as to an understanding of Wnt signal regulation via endoplasmic reticulum transport. Finally, this research was only possible through the trinity of pathology, endoscopic diagnosis, and organoid technology, and it can be said to be an achievement that greatly demonstrated the strength of cross-disciplinary collaboration at this university.

(Toshiro Sato and Masayuki Fujii, Department of Biochemistry)

Annals of Internal Medicine.    

2026 Jul 21. doi: 10.7326/ANNALS-25-05493.

Satoshi Takanashi, Koichiro Ohmura, Shuji Sumitomo, Hideki Oka, Kenta Misaki, Atsushi Ihata, Toshihiro Matsui, Shigeto Tohma, Jun Saegusa, Yuichiro Ota, Tsukasa Matsubara, Kunihiro Yamaoka, Koichi Amano, Yasuko Mori, Mitsuhiro Nishimura, Hanako Ishimaru, Hironari Hanaoka, Jun Kikuchi, Yasushi Kondo, Masaru Takeshita, Yuko Kaneko

Science Advances.

2026 Jun 5;12(23):eaeb2491. doi: 10.1126/sciadv.aeb2491.

Masaru Takeshita, Jun Inamo, Seiki Wakui, Ryosuke Nagashima, Takahiro Nishino, Kazuyuki Tsunoda, Satoshi Usuda, Hajime Inokuchi, Kazuyoshi Ishigaki, Takashi Sasaki, Yuki Kagoya, Katsuya Suzuki, Yuko Kaneko