Article
Engineering, Biomedical
Shogo Hashimoto, Narihito Nagoshi, Munehisa Shinozaki, Katsuyuki Nakanishi, Yu Suematsu, Takahiro Shibata, Momotaro Kawai, Takahiro Kitagawa, Kentaro Ago, Yasuhiro Kamata, Kaori Yasutake, Ikuko Koya, Yoshinari Ando, Aki Minoda, Tomoko Shindo, Shinsuke Shibata, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano
Summary: In this study, the therapeutic effect of environmental modulation on severe chronic spinal cord injury (SCI) was explored. The use of a clinically relevant hepatocyte growth factor (HGF)-releasing scaffold and human iPS cell-derived neural stem/progenitor cell (hNS/PCs) transplantation led to functional recovery. This study provides evidence for the feasibility of regenerative medicine strategies using clinically relevant materials in the treatment of severe chronic SCI.
Article
Pharmacology & Pharmacy
Fangliang Guo, Xiaolong Zheng, Ziyu He, Ruoying Zhang, Song Zhang, Minghuan Wang, Hong Chen, Wei Wang
Summary: The study found that long-term treatment with NMD helps to improve locomotion, pain-related behaviors, and spasticity-like symptoms in rats with SCI, but has less effect on open-field activity, hind limb grip strength, and bladder function. Additionally, NMD-treated rats showed greater tissue preservation, reduced lesion areas, and increased perilesional neuronal sparing, suggesting a potential therapeutic strategy for SCI treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Taoyang Yuan, Yu Shao, Xu Zhou, Qian Liu, Zhichao Zhu, Bini Zhou, Yuanchen Dong, Nicholas Stephanopoulos, Songbai Gui, Hao Yan, Dongsheng Liu
Summary: Researchers have developed a DNA hydrogel to repair spinal cord gap in rats, promoting proliferation and differentiation of stem cells for functional recovery. This hydrogel system shows great potential in clinical trials and could be adaptable to other tissue regeneration applications.
ADVANCED MATERIALS
(2021)
Article
Neurosciences
Ming-hao Ge, He Tian, Liang Mao, Dao-yong Li, Jia-quan Lin, Heng-shuo Hu, Shuo-cheng Huang, Chuan-jie Zhang, Xi-fan Mei
Summary: The study demonstrated that zinc can inhibit ferroptosis by regulating the NRF2/HO-1 and GPX4 signaling pathways, exerting a neuroprotective effect in spinal cord injury.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Neurosciences
Wei-wei Deng, Guang-yan Wu, Ling-xia Min, Zhou Feng, Hui Chen, Ming-liang Tan, Jian-feng Sui, Hong-liang Liu, Jing-ming Hou
Summary: Activation of glutamate neurons in the primary motor cortex can significantly improve motor function scores in rats, shorten the incubation period of motor evoked potentials, and increase motor potentials' amplitude. Accurate activation of the primary motor cortex can effectively promote tissue recovery and neurofilament growth, while also increasing the content of some growth-related proteins at the injured site. These findings suggest that selective activation of glutamate neurons in the primary motor cortex may play a significant role in promoting functional recovery after SCI and understanding the neural cell mechanism involved in recovery induced by motor cortex stimulation.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Shan-Shan Li, Bai-Yu Zhang, Sai-Ge Yin, Zi-Qi Wei, Nai-Xin Liu, Yi-Lin Li, Si-Yu Wang, Yu-Heng Shi, Jian Zhao, Li-Juan Wang, Yue Zhang, Jun Sun, Ying Wang, Xin-Wang Yang
Summary: A new peptide, VD11, derived from the spinal cord of an endemic Chinese amphibian, has been found to promote structural and functional recovery after spinal cord injury through activation of the AMPK and AKT signaling pathways.
NEURAL REGENERATION RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Sisi Mi, Xue Wang, Jiaxin Gao, Yu Liu, Zhongquan Qi
Summary: After spinal cord injury (SCI), the microenvironment inhibits neural regeneration due to the abundance of inhibitory factors and lack of factors promoting nerve regeneration. This study developed a bioactive material, hp-SHED sheet, to mimic the natural spinal cord structure and enhance nerve cell attachment and migration. Implantation of hp-SHED sheet in SCI rats promoted nerve regeneration, axonal remyelination, and inhibited glial scarring, leading to the restoration of sensory and motor functions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yiyoung Kim, Eun Ji Roh, Hari Prasad Joshi, Hae Eun Shin, Hyemin Choi, Su Yeon Kwon, Seil Sohn, Inbo Han
Summary: BZA has shown neuroprotection and remyelination effects in central nervous system injuries. Research demonstrated that BZA could suppress inflammatory response, promote oligodendrocyte precursor cell differentiation, and reduce blood-spinal cord barrier disruption. BZA also improved locomotor recovery in rats with spinal cord injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Juri Kim, Hari Prasad Joshi, Seung Hun Sheen, Kyoung-Tae Kim, Jae Won Kyung, Hyemin Choi, Ye Won Kim, Su Yeon Kwon, Eun Ji Roh, Un Yong Choi, Seil Sohn, Yong Ho Kim, Chul-Kyu Park, Hemant Kumar, In-Bo Han
Summary: This study found that intrathecal injection of RvD3 significantly reduces inflammatory response in SCI mice, promotes neuroprotection, and enhances neurological functional recovery.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jian Zhao, Ailang Pang, Saige Yin, Meifeng Yang, Xuemei Zhang, Rong Zhang, Jingfei Liu, Yuanqi Gu, Shanshan Li, Yan Hu, Yue Zhang, Yingchun Ba, Buliang Meng, Xinwang Yang
Summary: OM-LV20 promotes structural and functional recovery of spinal cord injury by increasing neuronal survival, enhancing BDNF and TrkB expression, and regulating oxidative stress balance.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Clinical Neurology
Andreia G. Pinho, Susana Monteiro, Valentina Liberato, Diogo J. Santos, Jonas Campos, Jorge R. Cibra, Nuno A. Silva, Nidia de Sousa, Anton Barreiro-Iglesias, Antonio J. Salgado
Summary: This study aimed to understand the potential of baclofen as a treatment to promote recovery after spinal cord injury (SCI). The results showed that baclofen can improve locomotor and bladder function control in mice after SCI, and it may modulate the immune response. Although further research is needed to explore the mechanisms behind the functional improvements produced by baclofen, this study opens up new avenues for designing pharmacological strategies to promote SCI recovery.
Article
Medicine, Research & Experimental
Gaetan Poulen, Emilie Aloy, Claire M. Bringuier, Nadine Mestre-Frances, Emaelle V. F. Artus, Maida Cardoso, Jean-Christophe Perez, Christophe Goze-Bac, Hassan Boukhaddaoui, Nicolas Lonjon, Yannick N. Gerber, Florence E. Perrin
Summary: By using the CSF1R inhibitor GW2580, transient reduction of microglia proliferation can improve motor function recovery in SCI patients. The treatment also helps reduce neuroinflammation and enhance tissue protection.
Article
Neurosciences
Sadayuki Ito, Tomoya Ozaki, Masayoshi Morozumi, Shiro Imagama, Kenji Kadomatsu, Kazuma Sakamoto
Summary: PTPRσ functions as a molecular switch regulating axonal regeneration in response to different glycan ligands. Enoxaparin, a heparin oligosaccharide, induces clustering and inactivation of PTPRσ, promoting axonal growth. Systemic administration of enoxaparin improves anatomical recovery and motor function without causing obvious hemorrhage after optic nerve and spinal cord injuries in rats.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Clinical Neurology
Zhihua Wang, Zhiwu Wu, Zhiping Xie, Wu Zhou, Meihua Li
Summary: This study found that Met can have a neuroprotective effect on the repair of traumatic spinal cord injury by inhibiting ferroptosis, improving long-term outcomes and reducing locomotor deficits.
WORLD NEUROSURGERY
(2022)
Article
Immunology
Yu Suematsu, Narihito Nagoshi, Munehisa Shinozaki, Yoshitaka Kase, Yusuke Saijo, Shogo Hashimoto, Takahiro Shibata, Keita Kajikawa, Yasuhiro Kamata, Masahiro Ozaki, Kaori Yasutake, Tomoko Shindo, Shinsuke Shibata, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano
Summary: The study demonstrates that a dual therapeutic intervention utilizing HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.
INFLAMMATION AND REGENERATION
(2023)
Review
Genetics & Heredity
Naoki Suzuki, Ayumi Nishiyama, Hitoshi Warita, Masashi Aoki
Summary: This article reviews the current knowledge of causative genes in ALS, summarizes the genetic mutations identified in familial ALS and their clinical features, and discusses the prospects and ethical issues of gene therapy development based on disease-modifying genes. It also explores the potential of axonal pathology as new therapeutic targets of ALS and highlights important pathological states of cell bodies.
JOURNAL OF HUMAN GENETICS
(2023)
Review
Clinical Neurology
Daisuke Ito, Satoru Morimoto, Shinichi Takahashi, Kensuke Okada, Jin Nakahara, Hideyuki Okano
Summary: Significant progress has been made in drug screening for amyotrophic lateral sclerosis using patient-derived induced pluripotent stem cells, leading to the identification of candidate drugs and the advancement of clinical trials. This stem cell-based approach shows safety and positive effects, reducing costs and time compared to animal testing.
Article
Biotechnology & Applied Microbiology
Ryota Tamura, Hiroyuki Miyoshi, Kent Imaizumi, Masahiro Yo, Yoshitaka Kase, Tsukika Sato, Mizuto Sato, Yukina Morimoto, Oltea Sampetrean, Jun Kohyama, Munehisa Shinozaki, Atsushi Miyawaki, Kazunari Yoshida, Hideyuki Saya, Hideyuki Okano, Masahiro Toda
Summary: This study demonstrates the potential benefit of gene-edited induced pluripotent stem cells (iPSCs) for the treatment of invasive glioma stem cells (GSCs). Neural stem cells (NSCs) derived from CRISPR/Cas9-edited iPSCs expressing a suicide gene showed enhanced tumor-trophic migratory capacity and significant in vivo antitumor effects. The study also identified key signaling pathways and gene expressions associated with the efficacy of therapeutic iPSC-NSCs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Satoru Morimoto, Koichi Saeki, Masaru Takeshita, Kunio Hirano, Mariko Shirakawa, Yumiko Yamada, Shiho Nakamura, Fumiko Ozawa, Hideyuki Okano
Summary: The study developed an intranasal vaccine for COVID-19 by using a Sendai virus vector loaded with the receptor binding domain of SARS-CoV-2 as an antigen. The vaccine induced a strong immune response, with increased levels of S-RBD-specific antibodies in serum and bronchoalveolar lavage fluid. The booster dose further enhanced the production of neutralizing antibodies, indicating the effectiveness of the vaccine.
Article
Cell Biology
Sho Yoshimatsu, Mayutaka Nakajima, Iki Sonn, Rie Natsume, Kenji Sakimura, Ena Nakatsukasa, Toshikuni Sasaoka, Mari Nakamura, Takashi Serizawa, Tsukika Sato, Erika Sasaki, Hongkui Deng, Hideyuki Okano
Summary: This study compared the gene expression profiles of mouse, human, and common marmoset EPSCs using transcriptomic approaches. The marmoset EPSC-like cells displayed a distinct morphology but exhibited a pluripotent state similar to embryonic stem cells. They also showed interspecies chimeric contribution to mouse embryos. Furthermore, the gene expression of the marmoset EPSC-like cells resembled that of human EPSCs. Overall, this study evaluated the efficacy of the method for deriving marmoset EPSCs.
Article
Biochemistry & Molecular Biology
Tosho Kondo, Ihori Ebinuma, Hirotaka Tanaka, Yukitoshi Nishikawa, Takaki Komiya, Mitsuru Ishikawa, Hideyuki Okano
Summary: In this study, an effective high-throughput screening system was established using induced pluripotent stem cells (iPSCs) to generate motor neurons. The generated motor neurons exhibited characteristics similar to ALS neurons and showed abnormal protein accumulation and hyperexcitability. Treatment with rapamycin and retigabine normalized activity and improved neuronal survival. This study provides a valuable platform for discovering novel ALS therapeutics and personalized medicine approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Shota Okura, Honoka Ishii, Ayano Suzuki, Chika Saegusa, Ko Fujiki, Kenshi Sugano, Noriomi Suzuki, Tsubasa Saeki, Saeko Matsuzaki, Hiroyuki Ozawa, Masato Fujioka, Makoto Hosoya, Hideyuki Okano
Summary: We have established two human-induced pluripotent stem cell (iPSC) lines from individuals without auditory disorders and confirmed normal hearing through extensive audiometry tests. These iPSC lines express pluripotency genes and are capable of differentiating into the three germ layers. They will be used as controls for pathological analysis and drug screening for ear disorders.
STEM CELL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Ryotaro Imai, Ryota Tamura, Masahiro Yo, Mizuto Sato, Mariko Fukumura, Kento Takahara, Yoshitaka Kase, Hideyuki Okano, Masahiro Toda
Summary: Despite limited treatment options for traumatic brain injury (TBI), neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) expressing yCD-UPRT showed promising results in functional recovery. The transplanted iPSC-derived NS/PCs displayed stable expression of the therapeutic gene and concentrated around the damaged cortex, leading to improved behavioral performance and prevention of secondary brain injury in a TBI mouse model. In addition, selective elimination of undifferentiated NS/PCs using 5-fluorocytosine (5-FC) demonstrated the safety of this regenerative medicine approach.
Article
Behavioral Sciences
Kazutoshi Konomatsu, Yosuke Kakisaka, Makoto Ishida, Temma Soga, Kazushi Ukishiro, Shin-ichiro Osawa, Kazutaka Jin, Masashi Aoki, Nobukazu Nakasato
Summary: The odyssey plot was used to visualize referral delays in epilepsy surgery. The study found that non-epileptologist's delay was significantly longer than other stages in the referral process, emphasizing the importance of early referral to epileptologists and the use of epilepsy monitoring units for early surgery.
EPILEPSY & BEHAVIOR
(2023)
Article
Biochemistry & Molecular Biology
Hitomi Ono-Minagi, Tsutomu Nohno, Takashi Serizawa, Yu Usami, Takayoshi Sakai, Hideyuki Okano, Hideyo Ohuchi
Summary: This study investigates the embryonic origin of salivary and lacrimal glands using transgenic mice and demonstrates that these glands contain cells derived from all three germ layers. Specifically, a subset of cells derived from neural crest differentiate into epithelial cells and express high levels of stem cell markers. These cells play an important role in the regenerative response following tissue damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Keigo Hikishima, Tomokazu Tsurugizawa, Kazumi Kasahara, Ryo Takagi, Kiyoshi Yoshinaka, Naotaka Nitta
Summary: Functional ultrasound (fUS) imaging provides a method for visualizing deep brain activity by measuring cerebral blood volume changes coupled with neural activity, while functional MRI (fMRI) relies on the blood-oxygenation-level-dependent signal. Resting-state functional MRI (rsfMRI) allows for whole brain functional imaging and estimation of resting-state networks (RSNs). Recent research suggests that fUS can provide similar RSNs to fMRI but with higher temporal resolution and stronger correlation with neural activity. These findings have the potential to advance our understanding of functional brain networks and their relationships with disease models.
Article
Clinical Neurology
Hiroya Kobayashi, Koji Ueda, Satoru Morimoto, Mitsuru Ishikawa, Nicolas Leventoux, Ryogen Sasaki, Yoshifumi Hirokawa, Yasumasa Kokubo, Hideyuki Okano
Summary: The proteins in extracellular vesicles derived from astrocytes in patients with Kii ALS/PDC exhibit distinctive patterns compared to healthy individuals, with increased proteins related to proteostasis and decreased proteins related to anti-inflammation.
NEUROLOGICAL SCIENCES
(2023)
Review
Medicine, General & Internal
Takahiro Shibata, Syoichi Tashiro, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi
Summary: Cell transplantation therapy using human-induced pluripotent stem cell-derived neural stem/progenitor cells has shown efficacy in treating the subacute phase of spinal cord injury. However, there is a lack of focus on treatment in the chronic phase, which poses challenges in overcoming factors specific to chronic SCI. Combining different therapies and addressing issues in severe injury models and functional recovery are important for regenerative therapy in chronic SCI.
MEDICINA-LITHUANIA
(2023)
Article
Geriatrics & Gerontology
Shohei Komaki, Masatoshi Nagata, Eri Arai, Ryo Otomo, Kanako Ono, Yukiko Abe, Hideki Ohmomo, So Umekage, Natsuko Shinozaki, Tsuyoshi Hachiya, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Yasumichi Arai, Nobuyoshi Hirose, Akio Yoneyama, Hideyuki Okano, Makoto Sasaki, Yae Kanai, Atsushi Shimizu
Summary: This study explored the epigenetic signatures of exceptional healthy longevity and found that it depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions.
LANCET HEALTHY LONGEVITY
(2023)
Review
Biochemistry & Molecular Biology
Hideyuki Okano, Satoru Morimoto, Chris Kato, Jin Nakahara, Shinichi Takahashi
Summary: In recent years, clinical trials using iPSC technology for disease modeling and drug discovery have shown promising results, particularly for the treatment of ALS. ROPi has been identified as a potential ALS treatment and has undergone clinical trials and reverse translational research, demonstrating its ability to delay disease progression and prolong survival in ALS patients.
JOURNAL OF NEUROCHEMISTRY
(2023)