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The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

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Neural regeneration Research 2024年第8期19卷 1751-1758页

作者： Dingyue Ju Chuanming Dong Department of Anatomy Medical College of Nantong UniversityNantongJiangsu ProvinceChina key laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina

spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous *** surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural *** treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal ***,there is a critical need to develop new treatments to promote functional repair after spinal cord *** recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord *** significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex *** led to the loading of three-dimensional bioprinting scaffolds which provided precise cell *** three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal *** this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting *** particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

关键词： biomaterials embryonic stem cells induced pluripotent stem cells mesenchymal stem cells nerve regeneration spinal cord injury stem cell therapy stem cells three-dimensional bioprinting

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Privacy-preserving integration of multiple institutional data for single-cell type identification with scPrivacy

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Science China(Life Sciences) 2023年第5期66卷 1183-1195页

作者： Shaoqi Chen Bin Duan Chenyu Zhu Chen Tang Shuguang Wang Yicheng Gao Shaliu Fu Lixin Fan Qiang Yang Qi Liu key laboratory of spine and spinal cord injury repair and regeneration(Tongji University) Ministry of EducationOrthopaedic Department of Tongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Department of AI WeBankShenzhen 518055China Translational Medical Center for Stem Cell Therapy and Institution for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Research Institute for Intelligent Autonomous Systems Shanghai 201210China

The rapid accumulation of large-scale single-cell RNA-seq datasets from multiple institutions presents remarkable opportunities for automatically cell annotations through integrative ***,the privacy issue has existed but being ignored,since we are limited to access and utilize all the reference datasets distributed in different institutions globally due to the prohibited data transmission across institutions by data regulation *** this end,we present scPrivacy,which is the first and generalized automatically single-cell type identification prototype to facilitate single cell annotations in a data privacy-preserving collaboration *** evaluated scPrivacy on a comprehensive set of publicly available benchmark datasets for single-cell type identification to stimulate the scenario that the reference datasets are rapidly generated and distributed in multiple institutions,while they are prohibited to be integrated directly or exposed to each other due to the data privacy regulations,demonstrating its effectiveness,time efficiency and robustness for privacy-preserving integration of multiple institutional datasets in single cell annotations.

关键词： preserving integration utilize

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Dynamic changes in intramedullary pressure 72 hours after spinal cord injury

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Neural regeneration Research 2019年第5期14卷 886-895页

作者： Xin Zhang Chang-Bin Liu De-Gang Yang Chuan Qin Xue-Chao Dong Da-Peng Li Chao Zhang Yun Guo Liang-Jie Du Feng Gao Ming-Liang Yang Jian-Jun Li School of Rehabilitation Medicine Capital Medical University Department of spinal and Neural Function Reconstruction China Rehabilitation Research Center Center of Neural injury and repair Beijing Institute for Brain Disorders China Rehabilitation Science Institute Beijing key laboratory of Neural injury and Rehabilitation

Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I(steep rise) 1–7 hours, stage Ⅱ(steady rise) 8–38 hours, and stage Ⅲ(descending) 39–72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages Ⅱ and Ⅲ of spinal cord injury.

关键词： nerve regeneration secondary spinal cord injury telemetry pathological mechanism rabbit conscious anesthetized hemorrhage edema pressure measurement blood-spinal barrier neural regeneration

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Application value of biofluid-based biomarkers for the diagnosis and treatment of spinal cord injury

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Neural regeneration Research 2022年第5期17卷 963-971页

作者： Hong-Da Wang Zhi-Jian Wei Jun-Jin Li Shi-Qing Feng Department of Orthopedics Tianjin Medical University General HospitalTianjinChina International Science and Technology Cooperation Base of spinal cord injury Tianjin Key Laboratory of Spine and Spinal CordTianjin Medical University General HospitalTianjinChina Department of Orthopedics Qilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Shandong University Center for Orthopedics Cheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina

Recent studies in patients with spinal cord injuries(SCIs)have confirmed the diagnostic potential of biofluid-based biomarkers,as a topic of increasing interest in relation to SCI diagnosis and *** paper reviews the research progress and application prospects of recently identified SCI-related *** structural proteins,such as glial fibrillary acidic protein,S100-β,ubiquitin carboxy-terminal hydrolase-L1,neurofilament light,and tau protein were correlated with the diagnosis,American spinal injury Association Impairment Scale,and prognosis of SCI to different *** factors,including interleukin-6,interleukin-8,and tumor necrosis factorα,are also good biomarkers for the diagnosis of acute and chronic SCI,while non-coding RNAs(micro RNAs and long non-coding RNAs)also show diagnostic potential for *** elements(Mg,Se,Cu,Zn)have been shown to be related to motor recovery and can predict motor function after SCI,while humoral markers can reflect the pathophysiological changes after *** factors have the advantages of low cost,convenient sampling,and ease of dynamic tracking,but are also associated with disadvantages,including diverse influencing factors and complex level *** various proteins have been verified as potential biomarkers for SCI,more convincing evidence from large clinical and prospective studies is thus required to identify the most valuable diagnostic and prognostic biomarkers for SCI.

关键词： biomarker diagnosis inflammatory cytokine motor recovery non-coding RNA prognosis spinal cord injury structural protein trace element

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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration

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Bioactive Materials 2021年第10期6卷 3097-3108页

作者： Penghui Zhang Xizhe Liu Peng Guo Xianlong Li Zhongyuan He Zhen Li Martin J.Stoddart Sibylle Grad Wei Tian Dafu Chen Xuenong Zou Zhiyu Zhou Shaoyu Liu Innovation Platform of regeneration and repair of spinal cord and Nerve injury Department of Orthopaedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen518107China Guangdong Provincial key laboratory of Orthopedics and Traumatology Orthopaedic Research Institute/Department of Spinal SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510080China AO Research Institute Davos Clavadelerstrasse 8Davos7270Switzerland laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsBeijing Research Institute of Orthopaedics and TraumatologyBeijing JiShuiTan HospitalBeijing100035China

It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains *** study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on *** mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 *** the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by *** results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(pregeneration in *** loading may be a promising biofabrication strategy for bone biomaterials.

关键词： Bioreactor Biofabrication Inflammatory microenvironment Bone biomaterials Macrophage polarization

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Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes

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Asian Journal of Pharmaceutical Sciences 2021年第6期16卷 806-815页

作者： Jiafu Mu Jiahe Wu Jian Cao Teng Ma Liming Li Shiqing Feng Jianqing Gao College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Pilot National laboratory for Marine Science and Technology Qingdao 266137China Department of Orthopedics Tianjin Medical University General HospitalTianjin 300052China International Science and Technology Cooperation Base of spinal cord injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjin 300052China Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China

Traumatic spinal cord injury is a fatal acute event without effective clinical *** the trauma,immediate neural protection and microenvironment mitigation are vitally important for nerve tissue repair,where stem cell-based therapies could be eclipsed by the deficiency of cells due to the hostile microenvironment as well as the transport and preservation *** emergency strategies are required to be convenient,biocompatible,and ***,we assess an emergency cell-free treatment using mesenchymal stem cell-derived exosomes,which have proven capable of comprehensive mitigation of the inhibitory lesion *** clinically validated fibrin glue is utilized to encapsulate the exosomes and in-situ gelates in transected rat spinal cords to provide a substrate for exosome delivery as well as nerve tissue *** emergency treatment alleviates the inflammatory and oxidative microenvironment,inducing effective nerve tissue repair and functional *** therapy presents a promising strategy for effective emergency treatment of central nervous system trauma。

关键词： Exosome Fibrin glue spinal cord injury Emergency treatment

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Activation of the Melanocortin-4 receptor signaling byα-MSH stimulates nervedependent mouse digit regeneration

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Cell regeneration 2021年第1期10卷 215-225页

作者： Hanqian Xu Hailin Zhang Yanqing Fang Huiran Yang Ying Chen Chao Zhang Gufa Lin key laboratory of spine and spinal cord injury repair and regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Stem Cell Institute University of MinnesotaMinneapolisMN 55455USA Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina

Background:Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and ***,the expression and function of Mc4r in the mouse limb and digit has not been fully *** previous work showed that Mc4r−/−mice fail to regenerate the digit,but whether activation of MC4R signaling could rescue digit regeneration,or stimulate proximal digit regeneration is not ***:We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp *** found that Mc4r-GFP is mainly expressed in the limb nerves,and in the limb muscles that are undergoing secondary *** of Mc4r-GFP in the adult mouse digit is restricted to the nail *** also examined the effect ofα-MSH on mouse digit *** found that administration ofα-MSH in the Mc4r+/−mice rescue the delayed regeneration of distal digit tip.α-MSH could rescue distal digit regeneration in denervated *** addition,α-MSH could stimulate regeneration of the proximally amputated digit,which is ***:Mc4r expression in the mouse limb and digit is closely related to nerve tissues,andα-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.

关键词： MC4R Mc4r-gfp α-MSH Digit regeneration Distal Proximal Denervation Neurotrophic function

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Autologous exosome facilitates load and target delivery of bioactive peptides to repair spinal cord injury

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Bioactive Materials 2023年第7期25卷 766-782页

作者： Ning Ran Wenxiang Li Renjie Zhang Caorui Lin Jianping Zhang Zhijian Wei Zonghao Li Zhongze Yuan Min Wang Baoyou Fan Wenyuan Shen Xueying Li Hengxing Zhou Xue Yao Xiaohong Kong Shiqing Feng Orthopedic Research Center of Shandong University&Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandongChina Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandongChina Tianjin key laboratory of spine and spinal cord National Spinal Cord Injury International Cooperation BaseDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Fujian key laboratory of laboratory Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina laboratory of Medical Molecular Virology School of MedicineNankai UniversityTianjinChina Tianjin key laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General HospitalTianjinChina

spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon *** effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord *** develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in *** importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI *** the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating *** is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.

关键词： spinal cord injury Targeted repair Autologous plasma exosome Drug loading Axon regeneration

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Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis

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Bioactive Materials 2023年第4期22卷 423-452页

作者： Zichang Liu Yu Zhuang Lianfei Fang Changyong Yuan Xudong Wang Kaili Lin Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China Shanghai Jiao Tong University School of Medicine Shanghai200025China key laboratory of spine and spinal cord injury repair and regeneration(Tongji University) Ministry of Education389 Xincun Road200065 ShanghaiPR China School of Stomatology Xuzhou Medical UniversityDepartment of Dental ImplantThe Affiliated Stomatological Hospital of Xuzhou Medical UniversityXuzhouChina

Osteoarthritis(OA)is a highly prevalent whole-joint disease that causes disability and pain and affects a patient’s quality of ***,currently,there is a lack of effective early diagnosis and *** stem cells can promote cartilage repair and treat OA,problems such as immune rejection and tumorigenicity *** vesicles(EVs)can transmit genetic information from donor cells and mediate intercellular communication,which is considered a functional paracrine factor of stem *** evidences suggest that EVs may play an essential and complex role in the pathogenesis,diagnosis,and treatment of ***,we introduced the role of EVs in OA progression by influencing inflammation,metabolism,and ***,we discussed EVs from the blood,synovial fluid,and joint-related cells for ***,we outlined the potential of modified and unmodified EVs and their combination with biomaterials for OA ***,we discuss the deficiencies and put forward the prospects and challenges related to the application of EVs in the field of OA.

关键词： Extracellular vesicles Osteoarthritis Biomarkers Diagnosis Treatment

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