Review
Biochemistry & Molecular Biology
Tianyuan Shi, Martin Cheung
Summary: Using rodents for modeling neurological diseases has limitations due to differences in genetics, neural development, and physiology between humans and rodents. In the past decade, induced pluripotent stem cells and induced neural stem cells generated through reprogramming somatic cells have offered a powerful alternative for studying disease pathogenesis and testing regenerative medicines. Urine-derived stem cells are an ideal cell source for reprogramming due to their proliferation, multipotency, epithelial nature, and ease of reprogramming.
CELL AND BIOSCIENCE
(2021)
Review
Cell Biology
Alexandra Benchoua, Marie Lasbareilles, Johana Tournois
Summary: Advances in human pluripotent stem cell biology have allowed for the creation of patient-specific human neurons, which provide unprecedented opportunities for investigating disease mechanisms and discovering new therapeutic strategies. These models help in identifying new molecular or functional targets for drug discovery and designing novel pharmacological approaches for rare genetic disorders, neurodegenerative diseases, and psychiatric disorders.
Review
Immunology
Takayuki Tanaka, Takeshi Shiba, Yoshitaka Honda, Kazushi Izawa, Takahiro Yasumi, Megumu K. Saito, Ryuta Nishikomori
Summary: The concept of autoinflammation refers to unprovoked episodes of inflammation without production of autoantibodies or autoreactive T cells. Induced pluripotent stem cells (iPSCs) have the potential to model diseases in vitro and be used for drug screening and cell replacement therapy. This review provides an overview of advances in research on autoinflammatory diseases using iPSC-derived monocytes/macrophages.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Shiya Lv, Enhui He, Jinping Luo, Yaoyao Liu, Wei Liang, Shihong Xu, Kui Zhang, Yan Yang, Mixia Wang, Yilin Song, Yirong Wu, Xinxia Cai
Summary: In vitro neural disease models using human-induced pluripotent stem cell-derived neurons (hiPSC-DNs) are being increasingly studied to understand pathogenesis and drug screening. Microelectrode arrays (MEAs) are emerging tools that can interface with 2D and 3D neural stem cell-derived in vitro models of the human brain to monitor their physiological activity in real time. This review comprehensively discusses the role of MEAs in analyzing hiPSC-DN established neural disease models and the advancements in using MEA technology to study these models, including epilepsy, autism spectrum developmental disorder (ASD), and others. The review also highlights the application of MEAs combined with hiPSC-DNs in detecting in vitro neurotoxic substances and discusses the future development of multifunctional and integrated devices for in vitro medical diagnostics and treatment.
Review
Biotechnology & Applied Microbiology
Wei Cheng, Chengming Fan, Qing Song, Ping Chen, Hong Peng, Ling Lin, Cong Liu, Bin Wang, Zijing Zhou
Summary: Fibrotic diseases are responsible for a third of global deaths, leading to organ remodeling and dysfunction. Despite the complications of organ transplantation, induced pluripotent stem cell (iPSC)-based therapy shows potential as a treatment option by replacing fibrotic organs. Recent studies have successfully differentiated iPSCs into fibrosis-relevant cell types with anti-fibrotic effects, providing promising precision treatments for organ-specific fibrosis. This review summarizes the potential, advantages, challenges, and future outlook of iPSC-based approaches in treating organ fibrosis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Endocrinology & Metabolism
Xin Wang, Mengxi Gao, Yali Wang, Yucheng Zhang
Summary: Diabetes is a complex metabolic disorder that requires new methods to restore pancreatic beta-cells. Pluripotent stem cells provide an ideal alternative source for generating these cells. This review systematically summarizes the progress, challenges, and future perspectives of using human pluripotent stem cells to treat diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Matan Sorek, Walaa Oweis, Malka Nissim-Rafinia, Moria Maman, Shahar Simon, Cynthia C. Hession, Xian Adiconis, Sean K. Simmons, Neville E. Sanjana, Xi Shi, Congyi Lu, Jen Q. Pan, Xiaohong Xu, Mahmoud A. Pouladi, Lisa M. Ellerby, Feng Zhang, Joshua Z. Levin, Eran Meshorer
Summary: The study suggests that transcriptional regulation imbalance may already be present at very early developmental stages of neurodegenerative diseases. Interventions aimed at this early phenotype may have high diagnostic value.
Review
Biochemistry & Molecular Biology
Giulia Paolini Sguazzi, Valentina Muto, Marco Tartaglia, Enrico Bertini, Claudia Compagnucci
Summary: Gene therapy traditionally used viral vectors for gene delivery, but recent advances in stem cell and gene therapy fields have revolutionized this approach, particularly with the combination of stem cell replacement therapy and gene editing technology, leading to a new era in gene therapy for neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Patrick Ernst, Philip A. A. Bidwell, Michaela Dora, David D. D. Thomas, Forum Kamdar
Summary: Human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are an important technological advancement in cardiovascular research, providing a renewable source of human cardiomyocytes for various applications. They offer unique insights into human physiology and pathophysiology, particularly in studying calcium regulation in the context of cardiovascular disease. However, the relative immaturity of hiPSC-CMs compared to adult cardiomyocytes remains a limitation, and efforts are being made to improve their maturity. This review provides a comprehensive overview of cardiomyocyte calcium cycling and hiPSC technology, focusing on our current understanding of calcium in hiPSC-CMs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Yumei Luo, Mimi Zhang, Yapei Chen, Yaoyong Chen, Detu Zhu
Summary: The outbreak of SARS-CoV-2 has caused a global public health crisis, highlighting the urgent need for biological models to study its pathology. iPSC-derived cellular and organoid models are ideal tools for in vitro simulation, drug screening, and long-term experiments in COVID-19 studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Juan Cen, Yichen Zhang, Yindu Bai, Shenqian Ma, Chuan Zhang, Lin Jin, Shaofeng Duan, Yanan Du, Yuqi Guo
Summary: Endometrial damage is a crucial factor in infertility, and traditional treatments have limited efficacy. Stem cell therapy has emerged as a promising new approach for the treatment of this disease. This paper summarizes the mechanisms by which stem cells repair endometrial damage and clarifies the underlying material basis of their effects. Furthermore, it explores research directions to address the limitations of clinical stem cell applications.
MATERIALS TODAY BIO
(2022)
Article
Cardiac & Cardiovascular Systems
Samantha K. Atkins, Abhijeet R. Sonawane, Romi Brouwhuis, Johana Barrientos, Anna Ha, Maximillian Rogers, Takeshi Tanaka, Takehito Okui, Shiori Kuraoka, Sasha A. Singh, Masanori Aikawa, Elena Aikawa
Summary: Cardiovascular calcification is a major predictor of cardiovascular events and a leading cause of global morbidity and mortality. This study presents a model of induced pluripotent stem cell-derived smooth muscle cells (iSMCs) for studying the pathogenesis of vascular calcification. The study successfully differentiated iPSCs into iSMCs and induced calcification in the iSMCs, providing an in vitro model for future research on cardiovascular calcification.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Cell Biology
Rebekka Kuhn, Aayushi Mahajan, Peter Canoll, Gunnar Hargus
Summary: Neurodegenerative dementias, including frontotemporal dementia, affect over 40 million people worldwide. The accumulation of tau protein in neurons and glial cells is a key feature of FTD, for which there is currently no cure. Research focuses on understanding the underlying mechanisms and potential therapeutic targets in these diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Reproductive Biology
Jinying Zhang, Minglei Zhi, Dengfeng Gao, Qianqian Zhu, Jie Gao, Gaoxiang Zhu, Suying Cao, Jianyong Han
Summary: This review summarizes the progress on the derivation of porcine pluripotent stem cells (PSCs) and reprogrammed cells. It also elucidates the mechanisms of pluripotency changes during pig embryo development. The potential applications of stable porcine PSCs and the guidance they provide for future research direction are also discussed.
BIOLOGY OF REPRODUCTION
(2022)
Review
Cell Biology
Kai-Li Wang, Qi Xue, Xun-Hong Xu, Fang Hu, Hong Shao
Summary: Cardiovascular diseases are the leading cause of death worldwide, and regenerative medicine offers promising treatments. However, current cardiac cell therapies require further optimization for improved effectiveness.
CELL AND TISSUE RESEARCH
(2021)
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
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
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
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
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
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)