@article{521501137839489fa297e992fcda6e34,
title = "LOTUS overexpression via ex vivo gene transduction further promotes recovery of motor function following human iPSC-NS/PC transplantation for contusive spinal cord injury",
abstract = "Functional recovery is still limited mainly due to several mechanisms, such as the activation of Nogo receptor-1 (NgR1) signaling, when human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PC) are transplanted for subacute spinal cord injury (SCI). We previously reported the neuroprotective and regenerative benefits of overexpression of lateral olfactory tract usher substance (LOTUS), an endogenous NgR1 antagonist, in the injured spinal cord using transgenic mice. Here, we evaluate the effects of lentiviral transduction of LOTUS gene into hiPSC-NS/PCs before transplantation in a mouse model of subacute SCI. The transduced LOTUS contributes to neurite extension, suppression of apoptosis, and secretion of neurotrophic factors in vitro. In vivo, the hiPSC-NS/PCs enhance the survival of grafted cells and enhance axonal extension of the transplanted cells, resulting in significant restoration of motor function following SCI. Therefore, the gene transduction of LOTUS in hiPSC-NS/PCs could be a promising adjunct for transplantation therapy for SCI.",
keywords = "LOTUS, Nogo receptor, axonal regrowth, ex vivo gene therapy, iPSC, motor function, regenerative medicine, spinal cord injury, transplantation",
author = "Shuhei Ito and Narihito Nagoshi and Yasuhiro Kamata and Kota Kojima and Satoshi Nori and Morio Matsumoto and Kohtaro Takei and Masaya Nakamura and Hideyuki Okano",
note = "Funding Information: We thank S. Yamanaka at CiRA (Kyoto University) for the human iPSCs (414C2). We are grateful for the assistance of H. Miyoshi, T. Okubo, Y. Hoshino, Y. Tanimoto, R. Shibata, K. Kajikawa, K. Ago, T. Kitagawa, and M. Kawai, who are all members of the spinal cord research team at the Department of Orthopedic Surgery and Physiology, Keio University School of Medicine, Tokyo, Japan.We also thank T. Harada, K. Yasutake, and M. Akizawa for their assistance with the experiments and animal care. This work was supported by the Japan Agency for Medical Research and Development ( AMED ) grant JP JJ P21bm0204001 (to H.O. and M.N.) and partly by The General Insurance Association of Japan Medical Research Grant on traffic accidents 16-1-20 . Funding Information: We thank S. Yamanaka at CiRA (Kyoto University) for the human iPSCs (414C2). We are grateful for the assistance of H. Miyoshi, T. Okubo, Y. Hoshino, Y. Tanimoto, R. Shibata, K. Kajikawa, K. Ago, T. Kitagawa, and M. Kawai, who are all members of the spinal cord research team at the Department of Orthopedic Surgery and Physiology, Keio University School of Medicine, Tokyo, Japan.We also thank T. Harada, K. Yasutake, and M. Akizawa for their assistance with the experiments and animal care. This work was supported by the Japan Agency for Medical Research and Development (AMED) grant JP JJ P21bm0204001 (to H.O. and M.N.) and partly by The General Insurance Association of Japan Medical Research Grant on traffic accidents 16-1-20. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = nov,
day = "9",
doi = "10.1016/j.stemcr.2021.09.006",
language = "English",
volume = "16",
pages = "2703--2717",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "11",
}