PT  - JOURNAL ARTICLE
AU  - Yoshida, Takashi
AU  - Tashiro, Syoichi
AU  - Nagoshi, Narihito
AU  - Shinozaki, Munehisa
AU  - Shibata, Takahiro
AU  - Inoue, Mitsuhiro
AU  - Ogawa, Shoji
AU  - Shibata, Shinsuke
AU  - Tsuji, Tetsuya
AU  - Okano, Hideyuki
AU  - Nakamura, Masaya
TI  - Chronic Spinal Cord Injury Regeneration with Combined Therapy Comprising Neural Stem/Progenitor Cell Transplantation, Rehabilitation, and Semaphorin 3A Inhibitor
AID  - 10.1523/ENEURO.0378-23.2024
DP  - 2024 Feb 01
TA  - eneuro
PG  - ENEURO.0378-23.2024
VI  - 11
IP  - 2
4099  - http://www.eneuro.org/content/11/2/ENEURO.0378-23.2024.short
4100  - http://www.eneuro.org/content/11/2/ENEURO.0378-23.2024.full
SO  - eNeuro2024 Feb 01; 11
AB  - Spinal cord injury (SCI) often results in various long-term sequelae, and chronically injured spinal cords exhibit a refractory feature, showing a limited response to cell transplantation therapies. To our knowledge, no preclinical studies have reported a treatment approach with results surpassing those of treatment comprising rehabilitation alone. In this study of rats with SCI, we propose a novel combined therapy involving a semaphorin 3A inhibitor (Sema3Ai), which enhances axonal regeneration, as the third treatment element in combination with neural stem/progenitor cell transplantation and rehabilitation. This comprehensive therapeutic strategy achieved significant improvements in host-derived neuronal and oligodendrocyte differentiation at the SCI epicenter and promoted axonal regeneration even in the chronically injured spinal cord. The elongated axons established functional electrical connections, contributing to significant enhancements in locomotor mobility when compared with animals treated with transplantation and rehabilitation. As a result, our combined transplantation, Sema3Ai, and rehabilitation treatment have the potential to serve as a critical step forward for chronic SCI patients, improving their ability to regain motor function.