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Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu stem cell Clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation institute of stem cell and Precision medicine DalianLiaoning ProvinceChina institute(College)of Integrative medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

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In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

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Neural Regeneration Research 2025年第8期20卷 2309-2310页

作者： Takashi Irie Taito Matsuda Department of stem cell biology and medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Neurology Neurological InstituteGraduate School of Medical SciencesKyushu UniversityFukuokaJapan

Stroke causes neuronal loss,which ultimately results in persistent neurological ***,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart *** that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

关键词： neonatal death therapeutic

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina institute for stem cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing institute for stem cell and regenerative medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for stem cells School of Life Sciences and TechnologyTongji University Translational Medical Center for stem cell Therapy and institute for regenerative medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab Shanghai Research institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Decline and fall of aging astrocytes:the human perspective

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Neural Regeneration Research 2025年第6期20卷 1713-1714页

作者： Alexei Verkhratsky Alexey Semyanov Faculty of biology Medicine and HealthThe University of ManchesterManchesterUK Department of Neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina Department of stem cell biology State Research Institute Centre for Innovative MedicineVilniusLithuania International Collaborative Center on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Department of Physiology Jiaxing University College of MedicineJiaxingZhejiang ProvinceChina

“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.

关键词： aging teeth progressive

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi James D.Guest Miller School of medicine University of MiamiMiamiFLUSA stem cell institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Role of Lef1 in sustaining self-renewal in mouse embryonic stem cells

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Journal of Genetics and Genomics 2010年第7期37卷 441-449页

作者： Chen Huang Dajiang Qin stem cell and Cancer biology Group Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China

Embryonic stem cells （ESCs） can self-renew indefinitely while maintaining the ability to generate all three germ-layer *** the importance of ESCs in developmental biology and their potential impact on regenerative medicine,the molecular mechanisms controlling ESC behavior are incompletely ***,activation of the canonical Wnt signaling pathway has been shown to contribute to mouse ESC *** we report that ectopic expression of Lef1,a component of the Wnt signaling pathway,has a positive effect on the self-renewal of mouse ***1 up-regulates Oct4 promoter activity and physically interacts with Nanog,two key components of the ESC pluripotency ***,siRNA for Lef1 induced mouse ESC *** results thus suggest that in response to Wnt signaling Lef1 binds to stabilized β-catenin and helps maintain the undifferentiated status of ESCs through modulation of Oct4 and Nanog.

关键词： embryonic stem cells Wnt signaling 13-catenin Lefl Oct4 Nanog

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Current approaches to reduce or eliminate mitochondrial DNA mutations

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Science China(Life Sciences) 2016年第5期59卷 532-535页

作者： Liang Yang Tingfang Mei Xiaobing Lin Haite Tang Yi Wu Rui Wang Jinglei Liu Zahir Shah Xingguo Liu Key Laboratory of regenerative biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Mitochondrial DNA （mtDNA） mutations have been impli- cated in a broad range of disorders which severely affect human health （Wallace, 1999）. Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA （nDNA）. Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions （60%-90%） before respiratory activity is affected （Schon et al., 2012）. It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell （iPSC） modeling. These various methods have their own advantages and limitations.

关键词：线粒体DNA突变基因突变 mtDNA突变线粒体疾病人类健康核DNA 多能干细胞病理变化

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Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming,and long non-coding RNAs

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Science Bulletin 2015年第20期60卷 1722-1733页

作者： Andrew Paul Hutchins Duanqing Pei Key Laboratory of regenerative biology South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangdong Provincial Key Laboratory of stem cell and regenerative medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Branch of the Supercomputing Center of Chinese Academy of Sciences South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Transposable elements(TEs) are mobile genomic sequences of DNA capable of autonomous and nonautonomous duplication. TEs have been highly successful,and nearly half of the human genome now consists of various families of TEs. Originally thought to be non-functional,these elements have been co-opted by animal genomes to perform a variety of physiological functions ranging from TE-derived proteins acting directly in normal biological functions, to innovations in transcription factor logic and influence on epigenetic control of gene expression. During embryonic development, when the genome is epigenetically reprogrammed and DNA-demethylated, TEs are released from repression and show embryonic stage-specific expression, and in human and mouse embryos, intact TEderived endogenous viral particles can even be detected. Asimilar process occurs during the reprogramming of somatic cells to pluripotent cells: When the somatic DNA is demethylated, TEs are released from repression. In embryonic stem cells(ESCs), where DNA is hypomethylated, an elaborate system of epigenetic control is employed to suppress TEs, a system that often overlaps with normal epigenetic control of ESC gene expression. Finally, many long non-coding RNAs(lnc RNAs) involved in normal ESC function and those assisting or impairing reprogramming contain multiple TEs in their RNA. These TEs may act as regulatory units to recruit RNA-binding proteins and epigenetic modifiers. This review covers how TEs are interlinked with the epigenetic machinery and lnc RNAs, and how these links influence each other to modulate aspects of ESCs,embryogenesis, and somatic cell reprogramming.

关键词： Transposable elements Endogenousretroviruses Embryonic stem cells lncRNA Reprogramming Pluripotency

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Induced pluripotent stem cell (iPS) technology:promises and challenges

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Chinese Science Bulletin 2009年第1期54卷 2-8页

作者： MIGUEL A Esteban Laboratory of regenerative biology South China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institute of Biomedicine and HealthChinese Academy of Sciences

In 2006,an article published in cell by Shinya Yamanaka took by surprise the stem cell research community. By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells,the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state. These cells,baptized iPS (induced pluripotent stem) cells,were immediately recognized as a ground-breaking discovery. Subsequently,the same authors and other groups reported a similar achievement with human fibroblasts. Two years later,the number of top quality papers on iPS is astonishing,and interest in the scientific community has risen to a fever pitch. But although iPS has the potential to revolutionize regenerative medicine,important questions still remain unanswered. Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS,and trying to improve the technique to make it suitable for the clinic. In this review article we briefly discuss the past,present and future of iPS,with emphasis on urgent issues to be solved.

关键词：自身更新多能性胚胎干细胞多能干细胞

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