First-in-human clinical study of an embryonic stem cell product for urea cycle disorders.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Umezawa Akihiro, Fukuda Akinari, Horikawa Reiko, Uchida Hajime, Enosawa Shin, Oishi Yoshie, Nakamura Naoko, Sasaki Kengo, Yanagi Yusuke, Shimizu Seiichi, Nakao Toshimasa, Kodama Tasuku, Sakamoto Seisuke, Hayakawa Itaru, Akiyama Saeko, Saku Noriaki, Miyata Shoko, Ite Kenta, Javaregowda Palaksha Kanive, Toyoda Masashi, Nonaka Hidenori, Nakamura Kazuaki, Ito Yoshikazu, Fukuhara Yasuyuki, Miyazaki Osamu, Nosaka Shunsuke, Nakabayashi Kazuhiko, Haga Chizuko, Yoshioka Takako, Masuda Akira, Ohkura Takashi, Yamazaki-Inoue Mayu, Machida Masakazu, Abutani-Sakamoto Rie, Miyajima Shoko, Akutsu Hidenori, Matsubara Yoichi, Igarashi Takashi, Kasahara Mureo
Аннотация
METHODS: Preclinical studies were conducted to validate the safety, biodistribution, and ammonia metabolism capabilities of HLCs using SCID mice models of UCD and extensive animal studies. In the clinical trial, five neonates with UCD received HLC infusions, intending to maintain metabolic stability and exceed a target weight of over 6 kg, which is considered necessary for safer liver transplantation.
RESULTS: Preclinical studies demonstrated that HLCs successfully engrafted in the liver without adverse migration or tumor formation and effectively elongated survival. Clinically, all five neonates exceeded the target weight of 6 kg while maintaining metabolic stability and successfully bridging to transplantation. Post-transplantation follow-up revealed stable growth, metabolic control, and no neurological complications.
CONCLUSIONS: The combined preclinical and clinical findings support HLC infusion as a viable bridge therapy for neonates with UCD, providing metabolic support to achieve safer weight thresholds for transplantation. While promising, careful monitoring remains essential, particularly for potential complications such as thrombus formation.
TRIAL REGISTRATION: jRCT, jRCT1090220412. Registered on 27 February 2019, https://jrct.niph.go.jp/en-latest-detail/jRCT1090220412 (originally registered in JMACCT (JMA-IIA00412)).