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Regeneration of dendritic cells in aged mice

cellular & Molecular Immunology 2010年第2期7卷 108-115页

作者： Serani LH van Dommelen Alexandra Rizzitelli Ann Chidgey Richard Boyd Ken Shortman Li Wu The Walter and Eliza Hall institute of Medical research Parkville Vic. Australia Monash Immunology and stem cell Laboratories Monash University Clayton Vic. Australia Current address: Department of Biochemistry and Molecular Biology Monash University Clayton Vic. Australia

Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells （DC） are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell （Treg） development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation （SSA）, and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration.

关键词： ageing dendritic cells thymic regeneration

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The long and winding road:homeostatic and disordered haematopoietic microenvironmental niches:a narrative review

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Biomaterials translational 2022年第1期3卷 31-54页

作者： Suzanne M.Watt stem cell research Nuffield Division of Clinical Laboratory SciencesRadcliffe Department of MedicineUniversity of OxfordOxfordUK Myeloma research Laboratory Adelaide Medical SchoolFaculty of Health and Medical SciencesUniversity of AdelaideAdelaideAustralia Cancer Program Precision Medicine ThemeSouth Australian Health and Medical Research InstituteAdelaideAustralia.

Haematopoietic microenvironmental niches have been described as the‘gatekeepers’for the blood and immune *** niches change during ontogeny,with the bone marrow becoming the predominant site of haematopoiesis in post-natal life under steady state *** determine the structure and function of different haematopoietic microenvironmental niches,it is essential to clearly define specific haematopoietic stem and progenitor cell subsets during ontogeny and to understand their temporal appearance and anatomical positioning.A variety of haematopoietic and non-haematopoietic cells contribute to haematopoietic stem and progenitor cell *** latter is reported to include endothelial cells and mesenchymal stromal cells(MSCs),skeletal stem cells and/or C-X-C motif chemokine ligand 12-abundant-reticular cell populations,which form crucial components of these microenvironments under homeostatic *** or deterioration of such cells contributes to significant clinical disorders and diseases worldwide and is associated with the ageing process.A critical appraisal of these issues and of the roles of MSC/C-X-C motif chemokine ligand 12-abundant-reticular cells and the more recently identified skeletal stem cell subsets in bone marrow haematopoietic niche function under homeostatic conditions and during ageing will form the basis of this research *** the context of haematopoiesis,clinical translation will deal with lessons learned from the vast experience garnered from the development and use of MSC therapies to treat graft versus host disease in the context of allogeneic haematopoietic transplants,the recent application of these MSC therapies to treating emerging and severe coronavirus disease 2019(COVID-19)infections,and,given that skeletal stem cell ageing is one proposed driver for haematopoietic ageing,the potential contributions of these stem cells to haematopoiesis in healthy bone marrow and the benefits and challenges of using this

关键词： ageing COVID-19 GvHD haematopoietic stem cell niche mesenchymal stromal cells rejuvenating niche skeletal stem cells

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Gene editing and its applications in biomedicine

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Science China(Life Sciences) 2022年第4期65卷 660-700页

作者： Guanglei Li Xiangyang Li Songkuan Zhuang Liren Wang Yifan Zhu Yangcan Chen Wen Sun Zeguang Wu Zhuo Zhou Jia Chen Xingxu Huang Jin Wang Dali Li Wei Li Haoyi Wang Wensheng Wei School of Life Science and Technology ShanghaiTech UniversityShanghai201210China Department of clinical Laboratory Shenzhen Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen518035China Shanghai Frontiers Science research Base of Genome Editing and cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai200241China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China University of Chinese Academy of Sciences Beijing100049China institute for stem cell and Regenerative Medicine Chinese Academy of SciencesBeijing100101China Biomedical Pioneering Innovation Center Beijing Advanced Innovation Center for GenomicsPeking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking UniversityBeijing100871China Gene Editing Center School of Life Science and TechnologyShanghaiTech UniversityShanghai201210China Bejing institute for stem cell and Regenerative Medicine Beijing100101China HIT Center for Life Sciences Harbin Institute of TechnologyHarbin150001China

The steady progress in genome editing, especially genome editing based on the use of clustered regularly interspaced short palindromic repeats(CRISPR) and programmable nucleases to make precise modifications to genetic material, has provided enormous opportunities to advance biomedical research and promote human health. The application of these technologies in basic biomedical research has yielded significant advances in identifying and studying key molecular targets relevant to human diseases and their treatment. The clinical translation of genome editing techniques offers unprecedented biomedical engineering capabilities in the diagnosis, prevention, and treatment of disease or disability. Here, we provide a general summary of emerging biomedical applications of genome editing, including open challenges. We also summarize the tools of genome editing and the insights derived from their applications, hoping to accelerate new discoveries and therapies in biomedicine.

关键词： gene editing CRISPR high-throughput functional genomics diagnostics animal model therapeutics

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Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2568-2580页

作者： Can Zhao Jia-Sheng Rao Hongmei Duan Peng Hao Junkui Shang Yubo Fan Wen Zhao Yudan Gao Zhaoyang Yang Yi Eve Sun Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing 100083China institute of Rehabilitation Engineering China Rehabilitation Science InstituteBeijing 100068China Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Beijing Advanced Innovation Centre for Biomedical Engineering Key Laboratory for Biomechanics and Mechanobiology of Chinese Education MinistrySchool of Biological Science and Medical EngineeringBeihang UniversityBeijing 10083China School of Engineering Medicine Beihang UniversityBeijing 10083China Shanghai institute of stem cell research and clinical translation Shanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Psychiatry and Biobehavioral Sciences UCLA Medical SchoolLos AngelesCA 90095USA

Spinal cord injury(SCI)is a severe damage usually leading to limb dysesthesia,motor dysfunction,and other physiological *** have previously shown that NT3-chitosan could trigger an acute SCI repairment in rats and non-human *** to the negative effect of inhibitory molecules in glial scar on axonal regeneration,however,the role of NT3-chitosan in the treatment of chronic SCI remains *** with the fresh wound of acute SCI,how to handle the lesion core and glial scars is a major issue related to chronic-SCI *** we report,in a chronic complete SCI rat model,establishment of magnetic resonancediffusion tensor imaging(MR-DTI)methods to monitor spatial and temporal changes of the lesion area,which matched well with anatomical *** of the lesion core via suction of cystic tissues and trimming of solid scar tissues before introducing NT3-chitosan using either a rigid tubular scaffold or a soft gel form led to robust neural regeneration,which interconnected the severed ascending and descending axons and accompanied with electrophysiological and motor functional *** contrast,cystic tissue extraction without scar trimming followed by NT3-chitosan injection,resulted in little,if any *** together,after lesion core clearance,NT3-chitosan can be used to enable chronic-SCI repair and MR-DTI-based mapping of lesion area and monitoring of ongoing regeneration can potentially be implemented in clinical studies for subacute/chronic-SCI repair.

关键词： scar NT3 wound

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FTO stabilizes MIS12 and counteracts senescence

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Protein & cell 2022年第12期13卷 954-960页

作者： Sheng Zhang Zeming Wu Yue Shi Si Wang Jie Ren Zihui Yu Daoyuan Huang Kaowen Yan Yifang He Xiaoqian Liu Qianzhao Ji Beibei Liu Zunpeng Liu Jing Qu Guang-Hui Liu Weimin Ci Xiaoqun Wang Weiqi Zhang State Key Laboratory of Brain and Cognitive Science CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of Brain-Intelligence Technology(Shanghai)Institute of BiophysicsChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for stem cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu HospitalCapital Medical UniversityBeijing 100053China Aging translational Medicine Center International Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China Chongqing Renji Hospital University of Chinese Academy of SciencesChongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing institute for Brain Disorders Beijing 100069China

Dear Editor, N6-methyladenosine(m6A)is an abundant epitranscriptomic modification that regulates messenger RNA(mRNA)*** m6A modification regulates mRNA splicing,transport,stability,and translation through coordinated activities by methyltransferases(writers),binding proteins(readers),and demethylases(erasers)(Huang et al.,2020;Wu et al.,2020).Among m6A regulators,fat mass of obesity-associ-ated protein(FTO),is the first discovered eraser with RNA m6A demethylation activity(Jia et al.,2011).Since then,FTO has been reported to play m6A-dependent roles in a variety of physiological processes including adipogenesis,neuro-genesis and tumorigenesis(Fischer et al.,2009;Li et al.,2017;Huang et al.,2020).Consequently,FTO deficiency in mice leads to dramatic phenotypes,such as decreased fat mass and impaired brain development(Fischer et al.,2009;Li et al.,2017).Similarly,inhibition of FTO reduces tumori-genesis in multiple types of cancer models,while FTO is highly expressed in many cancers(Huang et al.,2020).

关键词： Fischer impaired

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New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders:Combining with intranasal delivery

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3215-3232页

作者： Yaosheng Li Honghui Wu Xinchi Jiang Yunfei Dong Juanjuan Zheng Jianqing Gao institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.Li Dak Sum&Yip Yio Chin Center for stem cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China Hangzhou institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China

The clinical translation of stem cells and their extracellular vesicles(EVs)-based therapy for central nervous system(CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal(IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain-blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

关键词： stem cells Extracellular vesicles Central nervous system disorders Intranasal clinical translation Stroke Neurodegenerative disease Glioma

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Protein quality control of cell stemness

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cell Regeneration 2020年第1期9卷 259-269页

作者： Pengze Yan Jie Ren Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China China National Center for Bioinformation Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing institute for Brain Disorders Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China.

Protein quality control(PQC)systems play essential roles in the recognition,refolding and clearance of aberrant proteins,thus ensuring cellular protein homeostasis,or ***,continued proliferation and differentiation of stem cells require a high rate of translation;therefore,accurate PQC systems are essential to maintain stem cell *** evidence suggested crucial roles of PQC systems in regulating the stemness and differentiation of stem *** review focuses on current knowledge regarding the components of the proteostasis network in stem cells,and the importance of proteostasis in maintaining stem cell identity and regenerative functions.A complete understanding of this process might uncover potential applications in aging intervention and aging-related diseases.

关键词： Protein quality control stem cells stemness Chaperones Unfolded protein response Ubiquitinproteasome system Autophagy

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Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3230-3245页

作者： Xia Li Mi Shao Xiangjun Zeng Pengxu Qian He Huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou311121People’s Republic of China institute of Hematology Zhejiang UniversityHangzhouZhejiangPeople’s Republic of China Zhejiang Province Engineering Laboratory for stem cell and Immunity Therapy HangzhouZhejiangPeople’s Republic of China Center of stem cell and Regenerative Medicine Zhejiang University School of MedicineHangzhouPeople’s Republic of China

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune ***,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ ***,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the *** a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain *** the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of *** that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

关键词： cytokine release kinetics

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Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1412-1427页

作者： Jianpei Xu Yinzhe Sun Yang You Yuwen Zhang Dan Huang Songlei Zhou Yipu Liu Shiqiang Tong Fenfen Ma Qingxiang Song Chengxiang Dai Suke Li Jigang Lei Zhihua Wang Xiaoling Gao Jun Chen Shanghai Pudong Hospital&Department of Pharmaceutics School of PharmacyFudan UniversityShanghai 201203China Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China Department of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related GenesShanghai Universities Collaborative Innovation Center for Translational MedicineShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Emergency Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China institute of Science and Technology for Brain-Inspired Intelligence&Department of Neurology Fudan UniversityShanghai 201203China Department of Rehabilitation Medicine Huashan HospitalFudan UniversityShanghai 201203China Daxing research institute University of Science and Technology BeijingBiomedical Industry BaseZhongguancun Science and Technology ParkBeijing 102600China cellular Biomedicine Group Inc. Shanghai 201210China

Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical *** levels of deadly reactive oxygen radicals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs’*** on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC *** system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective *** this system,extracellular ROSscavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a microlivable niche at the level of a single MSC for ***,the infarct’s inanimate milieu is transformed at the tissue level into a new living niche to facilitate *** engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 *** vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

关键词： Ischemic stroke Mesenchymal stem cell cell engineering Hormesis effect Bioorthogonal chemistry Microglia Reactive oxygen spices Proinflammatory cytokines

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Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2202-2218页

作者： Huitong Ruan Yongfang Li Cheng Wang Yixu Jiang Yulong Han Yiwei Li Dandan Zheng Jing Ye Gang Chen Guo-yuan Yang Lianfu Deng Ming Guo Xingcai Zhang Yaohui Tang Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Jiaxing Key Laboratory of Basic research and clinical translation on Orthopedic Biomaterials Department of Orthopaedicsthe Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000China Department of Rehabilitation Medicine Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Med-X research institute and School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200030China School of Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA

Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar ***,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in ***,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into *** vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase *** work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

关键词： Central nervous system injuries Stroke Neural stem cell Neurogenesis Click chemistry Extracellular vesicles Microglia Targeted delivery

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