Cell therapy for spinal cord injury by using human iPSC-derived region-specific neural progenitor cells
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RESEARCH
Open Access
Cell therapy for spinal cord injury by using human iPSC-derived region-specific neural progenitor cells Keita Kajikawa1,2†, Kent Imaizumi1†, Munehisa Shinozaki1, Shinsuke Shibata3, Tomoko Shindo3, Takahiro Kitagawa1,2, Reo Shibata1,2, Yasuhiro Kamata1,2, Kota Kojima1,2, Narihito Nagoshi2, Morio Matsumoto2, Masaya Nakamura2* and Hideyuki Okano1*
Abstract The transplantation of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on spinal cord injury (SCI). However, while there are many subtypes of NPCs with different regional identities, the subtype of iPSC-derived NPCs that is most appropriate for cell therapy for SCI has not been identified. Here, we generated forebrain- and spinal cord-type NPCs from human iPSCs and grafted them onto the injured spinal cord in mice. These two types of NPCs retained their regional identities after transplantation and exhibited different graft-host interconnection properties. NPCs with spinal cord regional identity but not those with forebrain identity resulted in functional improvement in SCI mice, especially in those with mild-to-moderate lesions. This study highlights the importance of the regional identity of human iPSC-derived NPCs used in cell therapy for SCI. Keywords: Spinal cord injury, Stem cell therapy, Region-specific neural progenitors
Introduction Spinal cord injury (SCI) is a devastating and incurable disease, and basic treatment has not yet been developed. While many therapeutic options have been studied, neural progenitor cell (NPC) transplantation is one of the most promising choices for SCI treatment. It has been suggested that transplanted neural cells facilitate the regeneration of injured spinal cords by reconstructing local neural circuits, providing a scaffold for axonal growth, and supplying trophic support [1]. We and other groups have indeed demonstrated the efficacy of the transplantation of NPCs derived from induced pluripotent stem cells (iPSCs) * Correspondence: [email protected]; [email protected] † Keita Kajikawa and Kent Imaizumi contributed equally to this work. 2 Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan 1 Department of Physiology, 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
[2–7], and the first in-human clinical trial of iPSC-derived NPCs for SCI patients is expected to be conducted within a few years [8]. Before iPSC technology was established, undifferentiated cells derived from fetal tissues were intensively studied as the cell source for SCI treatment [9–13]. Indeed, many studies suggested that the functional improvement of SCI model animals was achieved by the transplantation of fetal cells with multiple origins, such as the spinal cord [9, 10], the forebrain [11, 12], and the peripheral tissues [13]. That said, it has been recently demonstrated that the original identi
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