Regenerative therapy for spinal cord injury using iPSC technology
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(2020) 40:40
Inflammation and Regeneration
REVIEW
Open Access
Regenerative therapy for spinal cord injury using iPSC technology Narihito Nagoshi1, Hideyuki Okano2 and Masaya Nakamura1*
Abstract Spinal cord injury (SCI) is a devastating event that causes permanent neurologic impairments. Cell transplantation therapy using neural precursor cells (NPCs) is a promising intervention aiming to replace damaged neural tissue and restore certain functions. Because the protocol to produce human induced pluripotent stem cells (iPSCs) was first established, we have attempted to apply this technology for regenerative therapy in SCI. Our group reported beneficial effects of iPSC-derived NPC transplantation and addressed safety issues on tumorigenicity after grafting. These findings will soon be tested at the clinical trial stage, the protocol of which has already been approved by the Ministry of Health, Labour and Welfare in Japan. Current transplantation therapies treat patients at the subacute phase after injury, highlighting the need for effective treatments for chronic SCI. We recently demonstrated the modest efficacy of gamma secretase inhibitor treatment of iPSC-NPCs before transplantation at the chronic phase. However, more comprehensive strategies involving combinatory therapies are essential to enhance current spinal cord regeneration treatments.
Background Spinal cord injury (SCI) occurs when spinal stability breaks down due to high-energy injuries sustained from events such as vehicular or contact sport accidents. The incidence of cervical SCI among the elderly has increased in recent years because of minor traumas such as falls. Current treatments for SCI primarily focus on surgery for spinal realignment and subsequent rehabilitation; however, there are no fundamental therapies to reverse damage to the spinal cord yet. We aimed to develop a treatment for this challenging pathology; thus, we conducted research exploring cell transplantation therapy using neural precursor cells (NPCs). Since the method for producing induced pluripotent stem cells (iPSCs) was first reported [1, 2], we have addressed our research specifically on the application of human iPSCs for regeneration therapy against SCI. Herein, we outline the efficacy and safety of
* Correspondence: [email protected] 1 Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Full list of author information is available at the end of the article
applying human iPSC-NPCs for SCI treatment, which is currently awaiting clinical application.
Transplantation therapy using iPSC-NPCs Around 10 years ago, we developed an induction method that could generate NPCs from iPSCs obtained from mice [3]. Because the NPCs produced from murine embryonic fibroblasts showed no undifferentiated cells in proliferated neurospheres in vitro, we transplanted them into injured murine spinal cords [4]. We found the grafted NPCs differentiated into three neural lineages without tumor formation. The differentiated oligode
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