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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental Biology Department of BiologyUniversity of PatrasPatrasGreece Laboratory of cellular and Molecular Neurobiology-stem cells Hellenic Pasteur InstituteAthensGreece Department of Physiology School of MedicineUniversity of PatrasPatrasGreece

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal ***,we extended our investigation in two clinically-relevant ***,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian ***,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of *** found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian *** agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver ***,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin *** results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by ***,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells(iPSCs) neurotrophic factors Parkinson's disease substantia

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Ionically Imprinting-Based Copper(Ⅱ)Label-Free Detection for Preventing Hearing Loss

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Engineering 2024年第2期33卷 276-282页

作者： Huan Wang Hui Zhang Xiaoli Zhang Hong Chen Ling Lu Renjie Chai The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033China State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda Hospital&Advanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging Department of Biomedical EngineeringShenzhen UniversityShenzhen 518060China Department of Otolaryngology Head and Neck Surgery Jiangsu Provincial Key Medical DisciplineNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Institute for stem cell and regeneration Chinese Academy of ScienceBeijing 100101China Beijing Key Laboratory of Neural regeneration and Repair Capital Medical UniversityBeijing 100069China

Copper is a microelement with important physiological functions in the ***,the excess copper ion(Cu^(2+))may cause severe health problems,such as hair cell apoptosis and the resultant hearing ***,the assay of Cu^(2+)is *** integrate ionic imprinting technology(IIT)and structurally colored hydrogel beads to prepare chitosan-based ionically imprinted hydrogel beads(IIHBs)as a low-cost and high-specificity platform for Cu^(2+)*** IIHBs have a macroporous microstructure,uniform size,vivid structural color,and magnetic *** incubated in solution,IIHBs recognize Cu^(2+)and exhibit a reflective peak change,thereby achieving label-free *** addition,benefiting from the IIT,the IIHBs display good specificity and selectivity and have an imprinting factor of 19.14 at 100μmol·L^(-1).These features indicated that the developed IIHBs are promising candidates for Cu^(2+)detection,particularly for the prevention of hearing loss.

关键词： Structural color Microfluidics Ionic imprinting Label-free detection Hearing loss

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A framework for the responsible reform of the 14-day rule in human embryo research

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Protein & cell 2022年第8期13卷 552-558页

作者： Yaojin Peng Jianwei Lv Zhenyu Xiao Lulu Ding Qi Zhou State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for stem cell and regeneration Chinese Academy of SciencesBeijing 100101China University of the Chinese Academy of Sciences Beijing 100049China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China

Ever since the world's first"test-tube"baby was bom in 1978,the use of human embryos in research has become highly controversial ethically and thus created a significant challenge for jurisdictions,especially in Europ... 详细信息

关键词： framework rule created

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Superparamagnetic iron oxide nanoparticle regulates microbiota-gut-inner ear axis for hearing protection

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National Science Review 2024年第6期11卷 273-284页

作者： Zhanhang Guo Yunhao Wu Bo Chen Mengdie Kong Peng Xie Yan Li Dongfang Liu Renjie Chai Ning Gu Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical EngineeringSoutheast University Medical Science and Technology Innovation Center Shandong First Medical University &Shandong Academy of Medical Sciences State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast University Institute of Materials Science and Devices School of Materials Science and Engineering Suzhou University of Science and Technology Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging &Interventional Radiology & Vascular Surgery Department of Radiology Medical School Zhongda Hospital Southeast University Co-Innovation Center of Neuroregeneration Nantong University School of Medical Technology Institute of Engineering MedicineBeijing Institute of Technology Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of China Institute for stem cell and regeneration Chinese Academy of Sciences Southeast university Shenzhen research institute Cardiovascular Disease Research Center Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Medical School Nanjing University

Noise-induced hearing loss(NIHL) is a highly prevalent form of sensorineural hearing damage that has significant negative effects on individuals of all ages and there are no effective drugs approved by the US Food and Drug Administration. In this study, we unveil the potential of superparamagnetic iron oxide nanoparticle assembly(SPIOCA) to reshape the dysbiosis of gut microbiota for treating NIHL. This modulation inhibits intestinal inflammation and oxidative stress responses, protecting the integrity of the intestinal barrier. Consequently, it reduces the transportation of pathogens and inflammatory factors from the bloodstream to the cochlea. Additionally, gut microbiota-modulated SPIOCA-induced metabolic reprogramming in the gut–inner ear axis mainly depends on the regulation of the sphingolipid metabolic pathway, which further contributes to the restoration of hearing function. Our study confirms the role of the microbiota–gut–inner ear axis in NIHL and provides a novel alternative for the treatment of NIHL and other microbiota dysbiosis-related diseases.

关键词： superparamagnetic iron oxide nanoparticle hearing loss gut microbiota inflammation sphingolipid metabolism microbiota–gut–inner ear axis

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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

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Neural regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of DaytonDaytonOHUSA Premedical Program University of DaytonDaytonOHUSA Center for Tissue regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA The Integrative Science and Engineering Center University of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe acute respiratory syndrome(SARS),cognitive dysfunction like brain fog,and cardiovascular ***-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer's disease remain *** the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye,we found that misexpression of nonstructural protein 3(Nsp3),a papain-like protease,ablates the eye and generates dark necrotic *** misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters,terminal deoxynucleotidyl transferase(TdT)dUTP Nick-end labeling(TUNEL)assay,and dihydroethidium ***,Nsp3 misexpression activates both apoptosis and autophagy mechanism(s)to regulate tissue *** expression of SARS-CoV2 Nsp3 in murine neuroblastoma,Neuro-2a cells,significantly reduced the metabolic activity of these cells and triggers cell *** of SARS-CoV2 Nsp3 in an Alzheimer's disease transgenic fly eye model(glass multiple repeats[GMR]>amyloidβ42)further enhances the neurodegenerative rough eye phenotype due to increased cell *** findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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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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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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A core scientific problem in the treatment of central nervous system diseases:newborn neurons

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Neural regeneration Research 2024年第12期19卷 2588-2601页

作者： Peng Hao Zhaoyang Yang Kwok-Fai So Xiaoguang Li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Guangdong-HongKong-Macao Institute of CNS regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult *** over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or ***,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system *** nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem *** of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than ***,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural *** have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming *** alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural *** can integration re plenish lost neurons after central nervous system injury,by improving the local *** regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn ***

关键词： bioactive materials brain trauma endogenous neurogenesis hippocampal dentate gyrus neural stem cells neurotrophic factors newborn neurons spinal cord injury stroke subventricular zone

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cellular metabolism and homeostasis in pluripotency regulation

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Protein & cell 2020年第9期11卷 630-640页

作者： Kun Liu Jiani Cao Xingxing Shi Liang Wang Tongbiao Zhao State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for stem cell and regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Pluripotent stem cells(PSCs)can immortally self-renew in culture with a high proliferation rate,and they possess unique metabolic characteristics that facilitate pluripotency ***,we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation,with particular emphasis on pathways involving amino acid metabolism,lipid metabolism,the ubiquitin-proteasome system and *** of amino acids and lipids is tightly coupled to epigenetic modification,organelle remodeling and cell signaling pathways for pluripotency *** harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular *** regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment.A more complete understanding of this balance will pave new ways to manipulate PSC fate.

关键词： autophagy amino acid metabolism lipid metabolism pluripotent stem cell(PSC) ubiquitinproteasome system(UPS)

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Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

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Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai State Key Laboratory of Oral&Maxillofacial Reconstruction and regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China Department of Implant Dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China State Key Laboratory of Oral&Maxillofacial Reconstruction and regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of Oral&Maxillofacial Reconstruction and regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan 430079China

stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells Bone development Epigenetics Ptip Glycolysis

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