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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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neural stem cells for Parkinson’s disease management:Challenges,nanobased support,and prospects

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World Journal of stem cells 2023年第7期15卷 687-700页

作者： Tuba Oz Ajeet Kaushik Małgorzata Kujawska Department of Toxicology Poznan University of Medical SciencesPoznan 60-631Poland NanoBioTech Laboratory Health System EngineeringDepartment of Environmental EngineeringFlorida Polytechnic UniversityLakelandFL 33805United States School of Engineering University of Petroleum and Energy StudiesDehradun 248007India

Parkinson’s disease(PD),characterized by loss of nigrostriatal dopaminergic neurons,is one of the most predominant neurodegenerative diseases affecting the elderly population *** concept of stem cell therapy in managing neurodegenerative diseases has evolved over the years and has recently rapidly *** stem cells(NSCs)have a few key features,including selfrenewal,proliferation,and multipotency,which make them a promising agent targeting *** is generally agreed that challenges for NSC-based therapy are present at every stage of the transplantation process,including preoperative cell preparation and quality control,perioperative procedures,and postoperative graft preservation,adherence,and overall therapy *** this review,we provided a comprehensive,careful,and critical discussion of experimental and clinical data alongside the pros and cons of NSC-based therapy in *** the state-of-the-art accomplishments of stem cell therapy,gene therapy,and nanotechnology,we shed light on the perspective of complementing the advantages of each process by developing nano-stem cell therapy,which is currently a research *** various obstacles and challenges remain,nano-stem cell therapy holds promise to cure PD,however,continuous improvement and development from the stage of laboratory experiments to the clinical application are necessary.

关键词： Parkinson’s disease Synuclein neural stem cells Nanomaterials Nano-stem cell therapy

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Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury

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neural Regeneration Research 2023年第9期18卷 1990-1998页

作者： Xiao-Yin Liu Yin-He Feng Qing-Bo Feng Jian-Yong Zhang Lin Zhong Peng Liu Shan Wang Yan-Ruo Huang Xu-Yi Chen Liang-Xue Zhou Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Tianjin Key Laboratory of Neurotrauma Repair Pingjin Hospital Brain CenterCharacteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Department of Respiratory and Critical Care Medicine People’s Hospital of Deyang CityAffiliated Hospital of Chengdu College of MedicineDeyangSichuan ProvinceChina Department of Liver Surgery&Liver Transplantation State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduProvinceChina Department of General Surgery the Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina The First Affiliated Hospital of Chengdu Medical College ChengduSichuan ProvinceChina Department of Anesthesiology Huashan HospitalFudan UniversityShanghaiChina Institute of Medical Security for Maritime Rights Protection of Characteristic Medical Center of Chinese People’s Armed Police Force TianjinChina

There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are *** combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain *** this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in *** scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for *** of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity *** addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured *** conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

关键词： 3D printing angiogenesis chitosan collagen exosomes functional recovery insulin-like growth factor-1 neural regeneration neural stem cells traumatic brain injury

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A three-dimensional matrix system containing melatonin and neural stem cells repairs damage from traumatic brain injury in rats

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neural Regeneration Research 2022年第11期17卷 2512-2517页

作者： Xuan-Yu Fang Da-Wei Zhao Chao Zhang Hong-Fei Ge Xu-Yang Zhang Feng-Chun Zhao Yi-Bin Jiang Hua Feng Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalArmy Medical UniversityChongqingChina

Brain lesions can cause neural stem cells to activate,proliferate,diffe rentiate,and migrate to the injured ***,after traumatic brain injury,brain tissue defects and microenvironment changes greatly affect the survival and growth of neural stem cells;the resulting reduction in the number of neural stem cells impedes effective repair of the injured *** can promote the survival,proliferation,and differentiation of neural stem cells under adverse conditions such as oxidative stress or hypoxia that can occur after traumatic brain ***,we investigated the therapeutic effects of melatonin combined with neural stem cells on traumatic brain injury in ***,in vitro studies confirmed that melatonin promoted the survival of neural stem cells deprived of oxygen and ***,we established a three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells and then used it to treat traumatic brain injury in *** found that treatment with the Matrigel system containing melatonin and neural stem cells decreased brain lesion volume,increased the number of surviving neuro ns,and improved recove ry of neurological function compared with treatment with Matrigel alone,neural stem cells alone,Matrigel and neural stem cells combined,and Matrigel and melatonin *** findings suggest that the three-dimensional Matrigelbased transplantation system containing melatonin and neural stem cells is a potential treatment for traumatic brain injury.

关键词： cell therapy magnetic resonance imaging Matrigel melatonin neural stem cells neurological function recovery three-dimensional transplantation traumatic brain injury

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Roles of neural stem cells in the repair of peripheral nerve injury

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neural Regeneration Research 2017年第12期12卷 2106-2112页

作者： Chong Wang Chang-feng Lu Jiang Peng Cheng-dong Hu Yu Wang Central Hospital of Handan Handan Hebei Province China Institute of Orthopedics Chinese PLA General Hospital Beijing China Co-Innovation Center of Neuroregeneration Nantong University Nantong Jiangsu Province China Beijing Key Lab of Regenerative Medicine in Orthopedics Beijing China Key Lab of Musculoskeletal Trauma & War Injuries of Chinese PLA Beijing China

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

关键词： nerve regeneration neural stem cells peripheral nerve regeneration Schwann-like cells neurons neurotrophic factors neuroprotection axons angiogenesis immune regulation neural regeneration

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Brain injury and neural stem cells

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neural Regeneration Research 2018年第1期13卷 7-18页

作者： Parker E.Ludwig Finosh G.Thankam Arun A.Patil Andrea J.Chamczuk Devendra K.Agrawal Department of Clinical and Translational Science Creighton University School of Medicine Department of Neurosurgery Creighton University School of Medicine

Many therapies with potential for treatment of brain injury have been investigated. Few types of cells have spurred as much interest and excitement as stem cells over the past few decades. The multipotentiality and self-renewing characteristics of stem cells confer upon them the capability to regenerate lost tissue in ischemic or degenerative conditions as well as trauma. While stem cells have not yet proven to be clinically effective in many such conditions as was once hoped, they have demonstrated some effects that could be manipulated for clinical benefit. The various types of stem cells have similar characteristics, and largely differ in terms of origin; those that have differentiated to some extent may exhibit limited capability in differentiation potential. stem cells can aid in decreasing lesion size and improving function following brain injury.

关键词： brain injury brain trauma infarction ischemia neural stem cells neuronal regeneration stroke

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Effects of primary microglia and astrocytes on neural stem cells in in vitro and in vivo models of ischemic stroke

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neural Regeneration Research 2021年第9期16卷 1677-1685页

作者： Sheng-Jun Wen Xi-Min Zheng Li-Fen Liu Na-Na Li Hai-An Mao Liang Huang Qiong-Lan Yuan Department of Neurology Shanghai Tongji HospitalTongji University School of MedicineShanghaiChina

Transplantation of neural stem cells(NSCs) can protect neurons in animal stroke models;however, their low rates of survival and neuronal differentiation limit their clinical application. Glial niches, an important location of neural stem cells, regulate survival, proliferation and differentiation of neural stem cells. However, the effects of activated glial cells on neural stem cells remain unclear. In the present study, we explored the effects of activated astrocytes and microglia on neural stem cells in vitro stroke models. We also investigated the effects of combined transplantation of neural stem cells and glial cells after stroke in rats. In a Transwell co-culture system, primary cultured astrocytes, microglia or mixed glial cells were exposed to glutamate or H_2O_2 and then seeded in the upper inserts, while primary neural stem cells were seeded in the lower uncoated wells and cultured for 7 days. Our results showed that microglia were conducive to neurosphere formation and had no effects on apoptosis within neurospheres, while astrocytes and mixed glial cells were conducive to neurosphere differentiation and reduced apoptosis within neurospheres, regardless of their pretreatment. In contrast, microglia and astrocytes induced neuronal differentiation of neural stem cells in differentiation medium, regardless of their pretreatment, with an exception of astrocytes pretreated with H_2O_2. Rat models of ischemic stroke were established by occlusion of the middle cerebral artery. Three days later, 5 × 10~5 neural stem cells with microglia or astrocytes were injected into the right lateral ventricle. neural stem cell/astrocyte-treated rats displayed better improvement of neurological deficits than neural stem cell only-treated rats at 4 days after cell transplantation. Moreover, neural stem cell/microglia-, and neural stem cell/astrocyte-treated rats showed a significant decrease in ischemic volume compared with neural stem celltreated rats. These findings indicate

关键词： astrocytes glutamate microglia neural stem cells neurogenesis neurons peroxide repair stroke

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Induced neuronal differentiation of neural stem cells by a combination of cytokines One-step versus two-step methods

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neural Regeneration Research 2009年第11期4卷 814-821页

作者： Xiaoli Sun Xue Chen Tianyi Zhang Zhenglin Jiang Weiwei Lin Ying Yuan XiaodongWang Department of Histology and Embryology Medical School of Nantong University Nantong 226001 Jiangsu Province China Affiliated Hospital of Nantong University Nantong 226001 Jiangsu Province China Jiangsu Province Key Laboratory of Neuroregeneration Nantong 226001 Jiangsu Province China

BACKGROUND： A combination of basic fibroblast growth factor （bFGF）, platelet-derived growth factor （PDGF）, human heregulin-beta-1, beta-mercaptoethanol retinoic acid and forskolin has been reported to induce the differentiation of rat bone marrow stromal cells into myelinating Schwann-like cells. OBJECTIVE： To investigate the inducing effects of a combination of bFGF, PDGF, human heregulin-beta-1, beta-mercaptoethanol retinoic acid and forskolin on neural stem cell differentiation by one- and two-step methods. DESIGN, TIME AND SETTING： A cytobiology experiment was performed at the Department of Histology and Embryology, Medical School of Nantong University, and Jiangsu Province Key Laboratory of Neuroregeneration, China, between August 2005 and January 2007. MATERIALS： A total of 30 healthy Sprague Dawley rat embryos at gestational days 14-16 were selected, bFGF, PDGF, human heregulin-beta-t, beta-mercaptoethanol, retinoic acid, and forskolin were purchased from Sigma, USA. METHODS： Passage 3 rat neural stem cells were cultured by a one-step method in serum-free medium plus 10 ng/m/bFGF, 5 ng/mL PDGF, 200 ng/mL heregulin-beta-1,35 ng/mL all-trans retinoic acid, and 5 pmol/L forskolin or by a two-step method in serum-free medium plus 35 ng/m/ all-trans retinoic acid for 72 hours, followed by serum-free medium plus 10 ng/mL bFGF, 5 ng/mL PDGF, 200 ng/mL heregulin-beta-t and 5 μmol/L forskolin. The control condition consisted of 10% fetal bovine serum alone or 20 ng/mL bFGF alone. MAIN OUTCOME MEASURES： Differentiated cells were identified by immunocytochemical staining for microtubule associate protein-2 （MAP2） and St 00 protein. Geometric parameters and sodium ion currents of the differentiated cells were measured by image analysis and whole-cell patch-clamp techniques, respectively. RESULTS： Compared with the two-step culture method, neuronal-like cells exhibited longer processes and a similar appearance to mature neurons using the one-step method. The percentage of

关键词： neural stem cells differentiation neuron cytokines whole-cell patch-clamp

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Metabolic and proteostatic differences in quiescent and active neural stem cells

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neural Regeneration Research 2024年第1期19卷 43-48页

作者： Jiacheng Yu Gang Chen Hua Zhu Yi Zhong Zhenxing Yang Zhihong Jian Xiaoxing Xiong Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Adult neural stem cells are neurogenesis progenitor cells that play an important role in ***,neural regeneration may be a promising target for treatment of many neurological *** regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and *** adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell *** adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural *** review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein ***,we discuss the physiological significance and underlying advantages of these diffe *** to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

关键词： adult neurogenesis cell metabolic pathway cellular proliferation neural stem cell niches neural stem cells neuronal differentiation nutrient sensing pathway proteostasis

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GID complex regulates the differentiation of neural stem cells by destabilizing TET2

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Frontiers of Medicine 2023年第6期17卷 1204-1218页

作者： Meiling Xia Rui Yan Wenjuan Wang Meng Zhang Zhigang Miao Bo Wan Xingshun Xu Department of Neurology The First Afiliated Hospital of Soochow UniversitySuzhou 215006China Institute of Neuroscience Soochow UniversitySuzhou 215006China Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow UniversitySuzhou 215123China

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells(NSC),which rely on the precise regulation of gene ***-eleven translocation 2(TET2)modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal ***,the regulation of TET2 in the process of neuronal differentiation remains ***,the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation,in contrast to mRNA *** identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient(GID)ubiquitin ligase complex,an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by *** protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC *** silencing of the core subunits of the GID complex,including WDR26 and ARMC8,attenuated the ubiquitination and degradation of TET2,increased the global 5-hydroxymethylcytosine levels,and promoted the differentiation of the ***2 level increased in the brain of the Wdr26^(+/-)*** results illustrated that the GID complex negatively regulates TET2 protein stability,further modulates NSC differentiation,and represents a novel regulatory mechanism involved in brain development.

关键词： TET2 GID complex neural stem cells differentiation of neurons

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