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3D printed collagen/silk fibroin scaffolds carrying the secretome of human umbilical mesenchymal stemcells ameliorated neurological dysfunction after spinal cord injury in rats

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regenerative Biomaterials 2022年第1期9卷 52-66页

作者： Chong Chen Hai-Huan Xu Xiao-Yin Liu Yu-Sheng Zhang Lin Zhong You-Wei Wang Lin Xu Pan Wei Ya-Xing Chen Peng Liu Chen-Ru Hao Xiao-Li Jia Nan Hu Xiao-Yang Wu Xiao-Song Gu Li-Qun Chen Xiao-Hong Li Academy of Medical Engineering and Translational medicine Tianjin University92 Weijin RoadNankai DistrictTianjin 300072China Tianjin Key Laboratory of Neurotrauma Repair Pingjin Hospital Brain CenterCharacteristic Medical Center of People’s Armed Police Forces220 Chenglin RoadDongli DistrictTianjin 300162China Department of Neurosurgery West China Medical SchoolWest China HospitalSichuan UniversityGuoxue Lane 37Wuhou DistrictChengduSichuan 610041China National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan University29 Wangjiang RoadWuhou DistrictChengduSichuan 610064China Department of Hematology The First Affiliated Hospital of Chengdu Medical College278 Baoguang Avenue middle sectionXindu DistrictChengduSichuan 610500China Medical Psychology Section Hubei General Hospital of Armed Police Force475 Minzhu RoadWuchang DistrictWuhanHubei 430071China Department of Neurosurgery The First People’s Hospital of Long Quan yi DistrictYuyang Road Yihe 3 GroupLongquanyi District201 Cheng DuSi Chuan 610000China

Although implantation of biomaterials carrying mesenchymal stem cells(MSCs)is considered as a promising strategy for ameliorating neural function after spinal cord injury(SCI),there are still some challenges including poor cell survival rate,tumorigenicity and ethics *** performance of the secretome derived from MSCs was more stable,and its clinical transformation was more *** antibody array demonstrated that the secretome of MSCs contained 79 proteins among the 174 proteins ***-dimensional(3D)printed collagen/silk fibroin scaffolds carrying MSCs secretome improved hindlimb locomotor function according to the Basso–Beattie–Bresnahan scores,the inclined-grid climbing test and electrophysiological *** with locomotor function recovery,3D printed collagen/silk fibroin scaffolds carrying MSCs secretome could further facilitate nerve fiber regeneration,enhance remyelination and accelerate the establishment of synaptic connections at the injury site compared to 3D printed collagen/silk fibroin scaffolds alone group according to magnetic resonance imaging,diffusion tensor imaging,hematoxylin and eosin staining,Bielschowsky’s silver staining,immunofluorescence staining and transmission electron *** results indicated the implantation of 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome might be a potential treatment for SCI.

关键词： spinal cord injury secretome mesenchymal stem cells 3D printing collagen silk fibroin

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Porous tantalum-composited gelatin nanoparticles hydrogel integrated with mesenchymal stem cell-derived endothelial cells to construct vascularized tissue in vivo

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regenerative Biomaterials 2021年第6期8卷 92-105页

作者： Zhenhua Zhao Mang Wang Fei Shao Ge Liu Junlei Li Xiaowei Wei Xiuzhi Zhang Jiahui Yang Fang Cao Qiushi Wang Huanan Wang Dewei Zhao Orthopaedic Department Affiliated ZhongShan Hospital of Dalian UniversityNo.6 Jiefang StreetZhongshan DistrictDalianLiaoning 116001P.R.China National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials Affiliated ZhongShan Hospital of Dalian UniversityNo.6 Jiefang StreetZhongshan DistrictDalianLiaoning 116001P.R.China Key State Laboratory of Fine Chemicals School of BioengineeringDalian University of TechnologyNo.2Linggong RoadHigh-Tech DistrictDalian 116024P.R.China School of Mechanical Engineering Dalian Jiaotong UniversityDalian 116028P.R.China Reproductive medicine Centre Affiliated ZhongShan Hospital of Dalian UniversityNo.6 Jiefang StreetZhongshan DistrictDalianLiaoning 116001P.R.China Department of Biomedical Engineering Faculty of Electronic Information and Electronical EngineeringDalian University of TechnologyDalian 116024P.R.China Laboratory Animal Center Affiliated ZhongShan Hospital of Dalian UniversityNo.6 Jiefang StreetZhongshan DistrictDalianLiaoning 116001P.R.China

The ideal scaffold material of angiogenesis should have mechanical strength and provide appropriate physiological microporous structures to mimic the extracellular matrix *** this study,we constructed an integrated three-dimensional scaffold material using porous tantalum(pTa),gelatin nanoparticles(GNPs)hydrogel,and seeded with bone marrow mesenchymal stem cells(BMSCs)-derived endothelial cells(ECs)for vascular tissue *** characteristics and biocompatibility of pTa and GNPs hydrogel were evaluated by mechanical testing,scanning electron microscopy,cell counting kit,and live-cell *** BMSCs-derived ECs were identified by flow cytometry and angiogenesis ***-derived ECs were seeded on the pTa-GNPs hydrogel scaffold and implanted subcutaneously in nude *** weeks after the operation,the scaffold material was evaluated by *** superior biocompatible ability of pTa-GNPs hydrogel scaffold was *** in vivo results suggested that 28 days after implantation,the formation of the stable capillary-like network in scaffold material could be promoted *** novel,integrated pTa-GNPs hydrogel scaffold is biocompatible with the host,and exhibits biomechanical and angiogenic ***,combined with BMSCs-derived ECs,it could construct vascular engineered tissue in *** study may provide a basis for applying pTa in bone regeneration and autologous BMSCs in tissue-engineered vascular grafts.

关键词： porous tantalum gelatin nanoparticles hydrogel bone marrow mesenchymal stem cell endothelial cell vascularization

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Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma

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Frontiers of medicine 2023年第2期17卷 240-262页

作者： Jing Feng Zheng Zhao Yanfei Wei Zhaoshi Bao Wei Zhang Fan Wu Guanzhang Li Zhiyan Sun Yanli Tan Jiuyi Li Yunqiu Zhang Zejun Duan Xueling Qi Kai Yu Zhengmin Cong Junjie Yang Yaxin Wang Yingyu Sun Fuchou Tang Xiaodong Su Chuan Fang Tao Jiang Xiaolong Fan Beijing Key Laboratory of Gene Resource and Molecular Development Laboratory of Neuroscience and Brain DevelopmentBeijing Normal UniversityBeijing 100875China Beijing Neurosurgical institute Beijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Pathology Affiliated Hospital of Hebei UniversityBaoding 071000China Gendya Biotechnology Ltd. Beijing 100176China Center of Growth Metabolism&Aging Key Laboratory of Bio-Resource and Eco-Environment of Ministry of EducationCollege of Life SciencesSichuan UniversityChengdu 610065China Department of Pathology Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China Biodynamic Optical Imaging Center(BIOPIC) School of Life SciencesPeking UniversityBeijing 100871China Department of Neurosurgery Affiliated Hospital of Hebei UniversityBaoding 071000China Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma Baoding 071000China Chinese Glioma Genome Atlas Network(CGGA) Beijing 100070China College of Life Sciences Sichuan Normal UniversityChengdu 610101China

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

关键词： glioma progression molecular classification EM PM subtyping intratumor heterogeneity

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干细胞再生生物学研究及临床应用的道德伦理问题探讨

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医学与社会 2016年第7期29卷 47-49,65页

作者：郭玲李忠光杨荣华薛雅卓王春慧 Hiroshi Takeshima MengMeng Xu 刘万红 Jianjie Ma William Isaacs 徐学红陕西师范大学生命科学学院西安710119 Kyoto University Kyoto Japan MSTP Duke University Medical Center Durham USA 武汉大学基础医学院武汉430030 Ohio State University School of medicine Columbus USA Johns Hopkins University Baltimore USA

干细胞具有分化为人类个体中250余种细胞的特性,该特性使再生生物学成为当今生命科学研究中最受瞩目的领域。美国和欧洲国家对干细胞研究的监管十分严格,其中一个重要原因是干细胞研究应用的道德伦理尚没有明确的界定。本文就以下几个... 详细信息

干细胞具有分化为人类个体中250余种细胞的特性,该特性使再生生物学成为当今生命科学研究中最受瞩目的领域。美国和欧洲国家对干细胞研究的监管十分严格,其中一个重要原因是干细胞研究应用的道德伦理尚没有明确的界定。本文就以下几个问题进行讨论:干细胞科学研究中的伦理道德问题,干细胞再生生物学应用前景引发的科研道德问题;克隆人类胚胎以解决器官移植的材料短缺,人类干细胞来源和"生命废料"是否具有生存权等干细胞临床应用的伦理学问题;制定的国际伦理准则或法则应该对未来干细胞成果引发的伦理问题有所预见。应尽快厘清干细胞研究、临床应用与伦理道德之间的关系,加快建立相应法律法规,保证干细胞再生生物学研究在世界范围内造福人类健康。

关键词：干细胞再生生物道德伦理法律法规

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造血干细胞基因治疗：进展与挑战

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中国科学：生命科学 2017年第12期47卷 1323-1335页

作者：张健萍程涛张孝兵中国医学科学院&北京协和医学院血液病医院(血液学研究所) 实验血液学国家重点实验室天津300020 中国医学科学院干细胞医学中心天津300020 北京协和医学院干细胞与再生医学系天津300020 肿瘤医学协同创新中心天津300020 Department of medicine Loma Linda UniversityLoma LindaCA 92350USA

造血干细胞具有自我更新和分化为各类血细胞的潜能,一直被认为是最理想的基因治疗靶细胞之一.近年来,基于慢病毒载体的造血干细胞基因治疗逐渐进入临床.同时,随着CRISPR-Cas9等基因编辑技术的不断发展,第二代造血干细胞精准基因治疗研... 详细信息

造血干细胞具有自我更新和分化为各类血细胞的潜能,一直被认为是最理想的基因治疗靶细胞之一.近年来,基于慢病毒载体的造血干细胞基因治疗逐渐进入临床.同时,随着CRISPR-Cas9等基因编辑技术的不断发展,第二代造血干细胞精准基因治疗研究已经取得重要进展,预计将逐渐开始临床转化.但目前,造血干细胞基因编辑还面临一些问题亟待解决,尤其是精准编辑效率还需要大幅度提高.

关键词：造血干细胞基因治疗基因编辑 CRISPR Cas9-sgRNA

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Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates

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World Journal of stem cells 2021年第5期13卷 452-469页

作者： Vladimir P Baklaushev Oleg V Durov Vladimir A Kalsin Eugene V Gulaev Sergey V Kim Ilya L Gubskiy Veronika A Revkova Ekaterina M Samoilova Pavel A Melnikov Dzhina D Karal-Ogly Sergey V Orlov Alexander V Troitskiy Vladimir P Chekhonin Alexander V Averyanov Jan-Eric Ahlfors Biomedical Research Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFMBA of RussiaMoscow 115682MoskvaRussia Department of Neurosurgery Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFMBAMoscow 115682MoskvaRussia Department of Anesthesiology N.N.Blokhin Russian Cancer Research CentreMoscow 115478MoskvaRussia Radiology and Clinical Physiology Scientific Research Center Federal center of brain research and neurotechnologies of the Federal Medical Biological AgencyMoscow 117997Russia Department of Neurobiology Serbsky National Medical Research Center for Psychiatry and NarcologyMoscow 119992MoskvaRussia Department of Primatology Russian Acad Med SciResearch Institute of Medical PrimatologySochi 119992SochiRussia Department of Vascular Surgery Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFMBA of RussiaMoscow 115682MoskvaRussia Department of Basic and Applied Neurobiology V.P.Serbsky Federal Medical Research Center for Psychiatry and NarcologyRussia Department of Medical Nanobiotechnology Pirogov Russian National Research Medical University(RNRMU)Moscow 115682MoskvaRussia New World Laboratories Laval H7V 4A7QuebecCanada

BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical *** reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first *** use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human *** To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of *** Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured *** resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid *** immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth *** Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after *** functional improvement described was not associated with neuronal differentiation of th

关键词： Direct cell reprogramming Neural precursor cells Directly reprogrammed neural precursor cells Spinal cord injury Nonhuman primates regenerative therapy,Evoked potentials

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研究神经胶质细胞的新兴技术

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神经损伤与功能重建 2020年第10期15卷 F0003-F0003页

作者： Hélène Hirbec Nicole Déglon Lynette C Foo Inbal Goshen Jaime Grutzendler Emilie Hangen Tirzah Kreisel Nathalie Linck Julien Muffat Sara Regio Sybille Rion Carole Escartin 杜一星 institute for Functional Genomics(IGF) University of MontpellierCNRSINSERMMontpellierFrance Laboratory of Neurotherapies and Neuromodulation Department of Clinical NeuroscienceLausanne University HospitalUniversity of LausanneLausanneSwitzerland Laboratory of Neurotherapies and Neuromodulation Neuroscience Research CenterLausanne University Hospital and University of LausanneLausanneSwitzerland Neuroimmunology and Neurodegeneration Section The Neuroscience and Rare Diseases Discovery and Translational AreaF.Hoffman-La RocheBaselSwitzerland Edmond and Lily Safra Center for Brain Sciences The Hebrew University of JerusalemJerusalemIsrael Department of Neurology Yale University School of MedicineNew HavenConnecticutUSA Department of Neuroscience Yale University School of MedicineNew HavenConnecticutUSA Commissariatà l'Energie Atomique et aux Energies Alternatives Département de la Recherche FondamentaleInstitut de Biologie François JacobMIRCenFontenay-aux-RosesFrance Centre National de la Recherche Scientifique Neurodegenerative Diseases LaboratoryUniversitéParis-SudUniversitéParis-SaclayUMR 9199Fontenay-aux-RosesFrance Program in Neurosciences and Mental Health The Hospital for Sick Childrenand Department of Molecular GeneticsThe University of TorontoTorontoCanada 不详

大脑的发育、生理功能和病理与神经元和不同类型的神经胶质细胞(如星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质细胞的前体细胞等)之间的相互作用密切相关。研究脑功能及其功能障碍,除了神经元之外,还需要对不同类型的神经胶质细... 详细信息

大脑的发育、生理功能和病理与神经元和不同类型的神经胶质细胞(如星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质细胞的前体细胞等)之间的相互作用密切相关。研究脑功能及其功能障碍,除了神经元之外,还需要对不同类型的神经胶质细胞进行研究。近年来,多项技术突破使“神经胶质科学家”能够解决新的具有挑战性的生物学问题。这些技术发展使得以中/高含量工作流研究特定细胞类型的作用成为可能,并在保存完好的环境中对其相互作用进行精细的分析。本综述阐明了几种可能揭示神经胶质细胞在特定脑功能或疾病中作用的尖端实验方法。这些实验方法包括高级细胞培养,诱导多能干细胞(iPSC)衍生的人神经胶质细胞,病毒载体,原位胶质细胞成像,光学遗传学和化学遗传学方法,以及高内涵分子分析。本文还阐述了某些技术的临床转化,通过特定的脑成像方法以监控患者的神经胶质细胞。本文亦讨论了每种技术的优点,缺陷和未来发展,并提供了选定的示例以说明现在如何可以解决特定的“胶质生物学”问题。

关键词：神经胶质细胞少突胶质细胞小胶质细胞星形胶质细胞脑功能细胞培养细胞类型脑成像

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