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Engineered Regeneration 2024年第1期5卷 11-20页

作者： Selina Beal Iain Stewart Paul Hatton Marysia placzek Ilida Ortega School of clinical Dentistry and Insigneo Institute Claremont CrescentUniversity of SheffieldSheffield S102TAUK School of Biosciences University of SheffieldEnglandUK National Heart and Lung Institute Imperial CollegeLondon SW36LYUK

Tanycytes are stem/progenitor cells that reside in the hypothalamus of the adult vertebrate *** can be cultured as free-floating neurospheres in vitro but tend to spontaneously differentiate over *** we asked whether morphological cues provided by engineered polymer scaffolds can modify spontaneous ***-derived neurospheres were cultured on electrospun scaffolds,prepared with either random or aligned fiber *** dispersed widely on the scaffolds,and-on aligned scaffolds-were highly organized,orientated parallel to the *** analysis showed that cells cultured on aligned scaffolds showed significantly greater expression of the neural stem/progenitor cell marker,NrCAM and reduced expres-sion of differentiated cell markers in comparison to those cultured on random *** this shows that tanycytes respond to local engineered cues,and that a morphologically constrained environment can better main-tain tanycytes as stem *** aligned scaffold culture system provides a powerful tool to better investigate this novel stem/progenitor cell population.

关键词： Scaffold Tanycytes Neural stem/progenitor cells Fiber alignment Electrospinning

The role and applications of extracellular vesicles in osteoporosis

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Bone Research 2024年第1期12卷 62-77页

作者： Fei Fang Jie Yang Jiahe Wang Tiantian Li Erxiang Wang Demao Zhang Xiaoheng Liu Chenchen Zhou Institute of Biomedical Engineering West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile *** intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological *** derived from various sources exert distinct effects on ***,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and ***,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone ***,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is ***,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in ***,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using ***,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

关键词： osteoporosis homeostasis biomaterials

XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

Mitochondrial components transferred by MSC-derived exosomes promoted bone regeneration under high salt microenvironment via DRP1/Wnt signaling

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Nano Research 2024年第9期17卷 8301-8315页

作者： Yiming Wang Shuai Lin Liujing Chen Mingzhao Li Zilu Zhu Zimeng Zhuang Meilian Cai Han Zhang Chenyang Xing Weiran Li Ruili Yang Department of Orthodontics School and Hospital of StomatologyPeking UniversityBeijing 100081China National clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology School and Hospital of StomatologyPeking UniversityBeijing 100081China Beijing Key Laboratory of Digital Stomatology School and Hospital of StomatologyPeking UniversityBeijing 100081China

Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ***,there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone *** this study,we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells,which resulted in impaired mitochondrial morphology and ***,this impairment hindered the bone formation of mesenchymal stem cells,resulting in osteopenia in ***,the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission,which inhibited the classical Wnt signaling ***,the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem *** study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery.

关键词： high salt dynamin-related protein 1 mitochondrial injury exosomes bone regeneration

Embryonic stem cell-derived extracellular vesicles rejuvenate senescent cells and antagonize aging in mice

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Bioactive Materials 2023年第11期29卷 85-97页

作者： Lu Yu Hang Wen Chang Liu Chen Wang Huaxin Yu Kaiyue Zhang Qingsheng Han Yue Liu Zhongchao Han Zongjin Li Na Liu School of Medicine Nankai UniversityTianjin300071China Key Laboratory of Bioactive Materials Ministry of EducationCollege of Life Sciences Nankai UniversityTianjin300071China Institute of stem cells Health-Biotech(Tianjin)Stem Cell Research Institute Co.LtdTianjin301700China

Aging is a degenerative process that leads to tissue dysfunction and *** stem cells(ESCs)have great therapeutic potential for age-related diseases due to their capacity for self-renewal and ***,the use of ESCs in clinical treatment is limited by immune rejection,tumourigenicity and ethical ***-derived extracellular vesicles(EVs)may provide therapeutic effects that are comparable to those of ESCs while avoiding unwanted ***,we fully evaluate the role of ESC-EVs in rejuvenation in vitro and in *** RNA sequencing(RNA-Seq)and microRNA sequencing(miRNA-Seq)screening,we found that miR-15b-5p and miR-290a-5p were highly enriched in ESC-EVs,and induced rejuvenation by silencing the Ccn2-mediated AKT/mTOR *** results demonstrate that miR-15b-5p and miR-290a-5p function as potent activators of rejuvenation mediated by *** rejuvenating effect of ESC-EVs was further investigated in vivo by injection into aged *** results showed that ESC-EVs successfully ameliorated the pathological age-related phenotypes and rescued the transcriptome profile of aged *** findings demonstrate that ESC-EVs treatment can rejuvenate senescence both in vitro and in vivo and suggest the therapeutic potential of ESC-EVs as a novel cell-free alternative to ESCs for age-related diseases.

关键词： treatment aging finding

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 594-604页

作者： Yanjin WANG Yifei CHEN Fuji YANG Xiaolong YU Ying CHU Jing ZHOU Yongmin YAN Jianbo XI Department of Laboratory Medicine Wujin Hospital Affiliated with Jiangsu UniversityJiangsu UniversityChangzhou 213017China Department of Laboratory Medicine School of MedicineJiangsu UniversityZhenjiang 212013China Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine Wujin Clinical College of Xuzhou Medical UniversityChangzhou 213017China

Liver fibrosis is a significant health burden,marked by the consistent deposition of ***,the currently available treatment approaches for this condition are far from *** oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver *** stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver *** studies have found that MSC-sEV can be used for microRNA delivery into target cells or *** is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC ***,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver *** study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis *** results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in ***,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in ***-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse ***-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 *** conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

关键词： Mesenchymal stem cell(MSC) Small extracellular vesicle(sEV) MicroRNA-4465(miR-4465) Hepatic stellate cell(HSC) Liver fibrosis

Optogenetics in oral and craniofacial research

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 656-671页

作者： Qinmeng ZHANG Luyao SONG Mengdie FU Jin HE Guoli YANG Zhiwei JIANG Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310000China Zhejiang University School of Medicine Hangzhou 310058China

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high *** modified photosensory sensors are engineered into proteins to modulate conformational changes with light ***,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral ***,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial *** addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational *** the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental *** future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.

关键词： Lasers Cell differentiation Bacterial virulence Nervous system Neurophysiology Behavioral science

Human umbilical cord-derived mesenchymal stem cells promote repair of neonatal brain injury caused by hypoxia/ischemia in rats

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Neural Regeneration Research 2022年第11期17卷 2518-2525页

作者： Yang Jiao Yue-Tong Sun Nai-Fei Chen Li-Na Zhou Xin Guan Jia-Yi Wang Wen-Juan Wei Chao Han Xiao-Lei Jiang Ya-Chen Wang Wei Zou Jing Liu stem Cell clinical Research Center National Joint Engineering LaboratoryRegenerative Medicine CenterThe First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of stem cells and Precision Medicine DalianLiaoning ProvinceChina Department of Neurology The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina College of Life Science Liaoning Normal UniversityDalianLiaoning ProvinceChina

Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde *** this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying *** established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of *** offspring were intranasally administe red hUC-MSCs on postnatal day *** found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain *** delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain *** findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.

关键词： developmental brain disease model disease-associated astrocytes intranasal administration lipopolysaccharide maternal immune activation neonatal brain injury neuroplasticity repair polypyrimidine tract-binding protein-1 stem cell therapy umbilical cord-derived mesenchymal stem cells

Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway

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Chinese Journal of Natural Medicines 2023年第7期21卷 540-550页

作者： HUANG Yu YANG Hui YANG Biying ZHENG Yu H OU Xiaomei CHEN Guiling ZHANG Wenqi ZENG Xiang DU Baoxin Labortory of stem Cell clinical Reaearch The Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510006China Labortory of stem Cell Biology and Chinese Medicine The Second Afiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China Labortory of stem Cell Biology and Chinese Medicine Guangdong Provincial Academy of Chinese Medical SciencesGuangzhou 510006China Labortory of stem Cell clinical Research Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510006China Department of Neurology Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510006China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal *** important aspect of ALS pathogenesis is superoxide dismutase 1(SOD1)mutant-mediated mitochondrial toxicity,leading to apoptosis in *** study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1(G-Rg1)and conditioned medium(CM)on a mutational SOD1 cell model,and to explore the underlying *** found that the contents of nerve growth factor,glial cell line-derived neurotrophic factor,and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells(hUCMSCs)were exposed to neuron differentiation reagents for seven *** or G-Rg1 decreased the apoptotic rate of SOD1^(G93A)-NSC34 cell to a certain extent,but their combination brought about the least apoptosis,compared with CM or G-Rg1 *** research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment *** associated with mitochondrial apoptotic pathways,such as Bax,caspase 9(Cas-9),and cytochrome c(Cyt c),were ***,CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B(NF-κB)signaling pathway by reducing the phosphorylation of p65 and Iκ***/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid(BetA),an agonist of the NF-κB signaling *** summary,the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^(G93A)-NSC34 cells through suppresing the NF-κB/Bcl-2 sgaling pathway(Fig.1 is a graphcal representation of the abstract).

关键词： Apoptosis Amyotrophic lateral sclerosis Conditioned medium Ginsenoside-Rg1 Umbilical cord mesenchymal stem cells

clinical Assessment of a Pharmaceutical Polyphenol Fruit Extract Gel to Inhibit Dental plaque

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Pharmacology & Pharmacy 2021年第9期12卷 177-189页

作者： Steven P. Goh David M. Goh E. Russell Vickers Suite 1 76A Archer St Chatswood NSW 2067 Australia clinical stem cells Sydney Australia

Oral bacteria (e.g. Porphyromonas gingivalis) are associated and potentially co-causative in several medical conditions including Alzheimer’s disease and increased cardiovascular risk. Naturally occurring polyphenols are a developing class of antimicrobial pharmaceutical agents. The use of plant-based polyphenol compounds is an attractive area of medical and dental research due to their high safety factor from their presence in vegetables and fruits. This preliminary study evaluated polyphenols found in berries to reduce bacterial dental plaque accumulation. The study was an in vivo single blind randomized controlled trial of seven subjects with a novel tooth gel using validated measurements. Results showed a significant reduction in plaque accumulation (p = 0.005) and a non-significant trend to reduce gingivitis (p = 0.08). The bioactive gel showed no local or systemic adverse effects and was well tolerated by subjects.

关键词： Dental plaque Gingivitis Polyphenol Quercetin Randomized Controlled Trial