RT Journal Article
SR Electronic
T1 Chronic Spinal Cord Injury Regeneration with Combined Therapy Comprising Neural Stem/Progenitor Cell Transplantation, Rehabilitation and Semaphorin 3A Inhibitor
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0378-23.2024
DO 10.1523/ENEURO.0378-23.2024
A1 Yoshida, Takashi
A1 Tashiro, Syoichi
A1 Nagoshi, Narihito
A1 Shinozaki, Munehisa
A1 Shibata, Takahiro
A1 Inoue, Mitsuhiro
A1 Ogawa, Shoji
A1 Shibata, Shinsuke
A1 Tsuji, Tetsuya
A1 Okano, Hideyuki
A1 Nakamura, Masaya
YR 2024
UL http://www.eneuro.org/content/early/2024/01/22/ENEURO.0378-23.2024.abstract
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 has the potential to serve as a critical step forward for chronic SCI patients, improving their ability to regain motor function.Significant Statement Spinal cord injury (SCI) sometimes results in a fatal condition that often results in multiple disabilities, including paralysis. Numerous treatment approaches have been investigated for acute-phase SCI in rodents, but reports on the treatment of the chronic phase are limited. We compared three synergistic treatment elements—transplantation, rehabilitation, and medication—to combined transplantation and rehabilitation in rats with chronic SCI. Before treatment, both groups had insufficient hindlimb function in open-field walking. Hindlimb function with axonal regeneration of host tissue significantly improved in the combined transplantation, rehabilitation, and medication group, whereas the combined transplantation and rehabilitation group showed no such improvement. These results suggest that the triple combined treatment improves locomotor function and has potential for improving gait appearance in chronic SCI patients.