Article
Cell & Tissue Engineering
Wenshu Zhou, Marta Silva, Chun Feng, Shumei Zhao, Linlin Liu, Shuai Li, Jingmei Zhong, Wenhua Zheng
Summary: This study demonstrates that the use of hpMSC-derived exosomes may constitute a promising therapeutic strategy for the treatment of SCI, significantly improving locomotor activity and bladder dysfunction in experimental animals. The exosomes promoted the activation of endogenous neural stem/progenitor cells and significantly increased neurogenesis.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell & Tissue Engineering
Desheng Kong, Baofeng Feng, Asiamah Ernest Amponsah, Jingjing He, Ruiyun Guo, Boxin Liu, Xiaofeng Du, Xin Liu, Shuhan Zhang, Fei Lv, Jun Ma, Huixian Cui
Summary: The study shows that using human iPSC-derived neural stem cells can promote neural functional recovery in mice with acute SCI, while also reducing fibrosis, glial scar formation, and inflammation.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Soo-Eun Sung, Min-Soo Seo, Young-In Kim, Kyung-Ku Kang, Joo-Hee Choi, Sijoon Lee, Minkyoung Sung, Sang-Gu Yim, Ju-Hyeon Lim, Hyun-Gyu Seok, Seung-Yun Yang, Gun-Woo Lee
Summary: This study demonstrated that exosomes isolated from human epidural adipose tissue-derived MSCs can help restore locomotor function in rats with SCI by reducing inflammatory response.
Review
Neurosciences
Yaqi Wu, Zhijian Tang, Jun Zhang, Yu Wang, Shengwen Liu
Summary: This study comprehensively lists the endogenous cells involved in SCI repair and summarizes the six most common mechanisms involved in SCI repair.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Cell Biology
Nicolas Guerout
Summary: Complete spinal cord injury leads to permanent deficits, but recent research has shown that the spinal cord has inherent plasticity and recovery potential. Different experimental paradigms have demonstrated that axonal regrowth is possible even after complete SCI, and recent findings have revealed that the glial scar is composed of multiple cellular populations, each playing specific roles after SCI.
Article
Materials Science, Biomaterials
Wenhua He, Xuanxuan Zhang, Xiangzhe Li, Dingyue Ju, Tiantian Mao, Yan Lu, Yu Gu, Longju Qi, Qinghua Wang, Qinfeng Wu, Chuanming Dong
Summary: This study constructed a novel composite scaffold consisting of decellularized spinal cord extracellular matrix-gel (DSCG) and GelMA hydrogel, which effectively promoted motor function recovery and neuronal differentiation, reduced inflammation, and inhibited reactive astrocyte proliferation in rats with spinal cord injury.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Weidong Wu, Shuaijun Jia, Hailiang Xu, Ziheng Gao, Zhiyuan Wang, Botao Lu, Yixiang Ai, Youjun Liu, Renfeng Liu, Tong Yang, Rongjin Luo, Chunping Hu, Lingbo Kong, Dageng Huang, Liang Yan, Zhimou Yang, Lei Zhu, Dingjun Hao
Summary: A strategy of using PDGF-MP hydrogel microspheres instead of bulk hydrogels can enhance the efficiency of PDGF-MP in activating its receptor, thus improving the therapeutic ability of neural stem cells (NSCs) in treating spinal cord injuries (SCI). In vitro experiments showed that PDGF-MP hydrogel microspheres maintained the proliferation and inhibited the apoptosis of NSCs in the presence of myelin extracts. In vivo experiments demonstrated that PDGF-MP hydrogel microspheres inhibited inflammatory cell infiltration and cell apoptosis, and promoted axonal regeneration, synapse formation, and angiogenesis in SCI rats.
Article
Pharmacology & Pharmacy
Ning He, Gerong Shen, Xiaoqin Jin, Heyangzi Li, Jingyu Wang, Lintao Xu, Jun Chen, Xi Cao, Chunyan Fu, Dongling Shi, Xinghui Song, Shuangshuang Liu, Yanwei Li, Tengfei Zhao, Jun Li, Jinjie Zhong, Yueliang Shen, Mingzhi Zheng, Ying-ying Chen, Lin-lin Wang
Summary: Spinal cord injury can alter the gut microbiota and metabolites, affecting the prognosis of the injury. Resveratrol, with its anti-inflammatory properties, can restore the disrupted gut microbiota and increase the concentration of butyrate, promoting functional recovery after spinal cord injury.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Cell Biology
Hongli Chen, Yunhao Wang, Wenjun Tu, Hong Wang, Huijuan Yin, Hong Sha, Yingxin Li
Summary: After spinal cord injury, the combination of human umbilical cord mesenchymal stem cell transplantation and photobiomodulation significantly improved motor function, increased Nissl bodies, and promoted neurofilament repair. The in situ expression of NF-200 and glial fibrillary acidic protein in the damaged area was the highest in the combination treatment group.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Neurosciences
Xinyu Guo, Chao Jiang, Yongjie Zhang, Zhe Chen, Dingjun Hao, Haihong Zhang
Summary: This study evaluated the therapeutic effect of spermatogonial stem cells (SSCs) in a rat model with spinal cord injuries. The results showed that SSC transplantation significantly improved motor scores and evoked potentials and had a restorative effect on tissue cells. This suggests that SSC transplantation may be an effective program for spinal cord injury treatment.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Cell & Tissue Engineering
Katarzyna Pieczonka, Michael G. Fehlings
Summary: Spinal cord injury (SCI) has a significant impact on quality of life and finances. Neural stem/progenitor cell (NSPC) transplantation shows promise for spinal cord regeneration, but the integration of transplanted cells remains a challenge. This review proposes various techniques, including molecular cues and alternative methods, to guide the integration of grafted cells towards specific circuits. Future research in these areas may improve outcomes for SCI patients.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Yiyan Zheng, Chrystine M. Gallegos, Haipeng Xue, Shenglan Li, Dong H. Kim, Hongxia Zhou, Xugang Xia, Ying Liu, Qilin Cao
Summary: Recovering locomotor function after spinal cord injury (SCI) is crucial. Stem cell therapy, particularly using patient-specific induced pluripotent stem cells (iPSCs), holds promise as a reparative strategy. This study found that purified iPSC-derived neural progenitor cells (NPCs) were able to improve locomotor function in a rat model of cervical SCI.
Article
Cell & Tissue Engineering
Katarzyna Pieczonka, Hiroaki Nakashima, Narihito Nagoshi, Kazuya Yokota, James Hong, Anna Badner, Jonathon C. T. Chio, Shinsuke Shibata, Mohamad Khazaei, Michael G. Fehlings
Summary: Traumatic spinal cord injury (SCI) causes the loss of neurons and glial cells. Current interventions for SCI lack regenerative solutions. Neural stem/progenitor cell (NPC) transplantation is a promising strategy for regeneration but inconsistent differentiation hinders functional recovery. This study generated oligodendrogenically biased NPCs (oNPCs) from human induced pluripotent stem cells (hiPSCs) and demonstrated their effectiveness in a rodent model of cervical SCI, showing enhanced tissue preservation, remyelination, and functional recovery without adverse effects. These findings highlight the therapeutic potential of oNPCs in cervical SCI and call for further investigation to optimize this approach.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Materials Science, Biomaterials
Jun Zhou, Yaqi Wu, Zhijian Tang, Kaipeng Zou, Juan Chen, Zuowei Lei, Xueyan Wan, Yanchao Liu, Huaqiu Zhang, Yu Wang, Armin Blesch, Ting Lei, Shengwen Liu
Summary: Studies have shown that alginate capillary hydrogels can fill the lesion cavity and promote axonal regeneration after grafting into the injured spinal cord. Neural stem/progenitor cells (NSPCs) can survive, proliferate, and differentiate into neurons within the capillaries in vitro. In animal experiments, a portion of the grafted cells can survive and differentiate into neurons, astrocytes, and oligodendrocytes. Furthermore, the grafted cells can promote the growth of host axons, form putative synapses with host neurons, improve electrophysiological conductivity, and partially restore locomotor function.
REGENERATIVE BIOMATERIALS
(2022)
Article
Biology
Jianping Li, Zhisheng Ji, Yu Wang, Tiantian Li, Jinghua Luo, Jun Li, Xueshuang Shi, Liming Li, Liumin He, Wutian Wu
Summary: This study investigated the combined treatment of nano-hydrogel and human adipose-derived stem cells for spinal cord injury, showing that this approach can regulate inflammatory reaction, protect neurons and axons, and promote motor function recovery, providing evidence for clinical treatment.
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
Developmental Biology
Marie Sasaki, Takayuki Mitsuhashi, Fumiko Goto, Shinsuke Shibata, Ken-ichiro Kubo, Shinju Oku, Akihiro Owashi, Takao Takahashi
Summary: Maternal immune activation can disrupt cell cycle regulation in stem cells and impair higher cortical function in rodents. In humans, maternal immune activation during early pregnancy is strongly associated with increased risk of autism spectrum disorder in offspring. In a study with mice, in utero exposure to polyinosinic-polycytidylic acid (poly (I:C)) during early neuronogenesis resulted in increased differentiation of neural stem/progenitor cells (NSPCs) without changing the cell cycle length. This abnormal increase in differentiation reduced the population size of NSPCs and led to a thinner neocortex in the offspring due to decreased production of neurons. The timing and amount of poly (I:C) exposure during pregnancy can greatly affect cerebral cortical histogenesis.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Cell & Tissue Engineering
Takahiro Shibata, Syoichi Tashiro, Shinsuke Shibata, Munehisa Shinozaki, Tomoko Shindo, Shogo Hashimoto, Momotaro Kawai, Takahiro Kitagawa, Kentaro Ago, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi
Summary: The combined therapy of hiPSC-NS/PCs transplantation and rehabilitative training can promote functional recovery in chronic SCI by enhancing cell survival and neuronal differentiation, increasing the expressions of BDNF and NT-3 proteins, and promoting neuronal activity.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Cell & Tissue Engineering
Yuji Okano, Yoshitaka Kase, Hideyuki Okano
Summary: The emergence of single-cell RNA sequencing has revolutionized the study of cellular diversity. Conventional methods for annotating RNA-seq data have limitations in capturing universal characteristics of a cell type. This study presents a new framework for managing cellular identities based on set theory, allowing for comparisons across datasets while preserving biological semantics.
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
Developmental Biology
Takayuki Mitsuhashi, Satoko Hattori, Kimino Fujimura, Shinsuke Shibata, Tsuyoshi Miyakawa, Takao Takahashi
Summary: Valproic acid (VPA) is an antiepileptic drug that inhibits epileptic activity of neurons mainly through sodium channel inhibition and GABA transaminase inhibition. It also inhibits histone deacetylases, leading to epigenetic modifications of stem/progenitor cell characteristics and affecting fetal development. Clinical studies have shown that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in children. A study on mice revealed that in utero VPA exposure led to abnormal social interaction, cognitive changes, hypersensitivity to pain/heat, and impaired locomotor activity, resembling symptoms of autism spectrum disorder in humans.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Gastroenterology & Hepatology
Kazuki Natsui, Atsunori Tsuchiya, Risa Imamiya, Mayuko Osada-Oka, Yui Ishii, Yohei Koseki, Nobutaka Takeda, Kei Tomiyoshi, Fusako Yamazaki, Yuki Yoshida, Riuko Ohashi, Yiwei Ling, Koji Ueda, Nobuko Moritoki, Kazuhiro Sato, Takahiro Nakajima, Yoshinori Hasegawa, Shujiro Okuda, Shinsuke Shibata, Shuji Terai
Summary: This study investigated the role of outer-membrane vesicles (OMVs) in the pathogenesis of cirrhosis. OMVs derived from Escherichia coli induced inflammation, fibrosis, and suppression of albumin production, exacerbating liver inflammation and fibrosis. These findings have important implications for the prevention and treatment of cirrhosis.
LIVER INTERNATIONAL
(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
Biology
Miho Isoda, Tsukasa Sanosaka, Ryo Tomooka, Yo Mabuchi, Munehisa Shinozaki, Tomoko Andoh-Noda, Satoe Banno, Noriko Mizota, Ryo Yamaguchi, Hideyuki Okano, Jun Kohyama
Summary: A single-cell approach identified cellular properties of neural and mesenchymal origins in human induced pluripotent stem cells, shedding light on the causes of undesired grafts after transplantation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Emi Qian, Masahiro Uemura, Hiroya Kobayashi, Shiho Nakamura, Fumiko Ozawa, Sho Yoshimatsu, Mitsuru Ishikawa, Osamu Onodera, Satoru Morimoto, Hideyuki Okano
Summary: CARASIL is a inherited small vessel disease caused by mutations in the HTRA1 gene. Heterozygous mutations in HTRA1 have been found to cause clinical features of the disease. Researchers have successfully established a hiPSC line from a patient with heterozygous HTRA1-related CSVD, which has normal morphology and karyotype. The hiPSCs expressed pluripotency-related markers and had the ability to differentiate into all three germ layers in vitro, providing a valuable tool for studying the cellular mechanisms of HTRA1 mutation.
INFLAMMATION AND REGENERATION
(2023)
Article
Cell & Tissue Engineering
Katarzyna Pieczonka, Hiroaki Nakashima, Narihito Nagoshi, Kazuya Yokota, James Hong, Anna Badner, Jonathon C. T. Chio, Shinsuke Shibata, Mohamad Khazaei, Michael G. Fehlings
Summary: Traumatic spinal cord injury (SCI) causes the loss of neurons and glial cells. Current interventions for SCI lack regenerative solutions. Neural stem/progenitor cell (NPC) transplantation is a promising strategy for regeneration but inconsistent differentiation hinders functional recovery. This study generated oligodendrogenically biased NPCs (oNPCs) from human induced pluripotent stem cells (hiPSCs) and demonstrated their effectiveness in a rodent model of cervical SCI, showing enhanced tissue preservation, remyelination, and functional recovery without adverse effects. These findings highlight the therapeutic potential of oNPCs in cervical SCI and call for further investigation to optimize this approach.
STEM CELLS TRANSLATIONAL MEDICINE
(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)
