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| 1 | Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes:current perspectives and future challenges显示文摘Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed. | Dinh Ha Ningning Yang Venkatareddy Nadithe | 2016 | Acta Pharmaceutica Sinica B2016，6，4： | 104 |
| 2 | Mesenchymal stromal cells-exosomes:a promising cell-free therapeutic tool for wound healing and cutaneous regeneration显示文摘Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerves,and blood vessels.Mesenchymal stromal cells(MSCs)take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans.Exosomes,which are among the key products MSCs release,mimic the effects of parental MSCs.They can shuttle various effector proteins,messenger RNA(mRNA)and microRNAs(miRNAs)to modulate the activity of recipient cells,playing important roles in wound healing.Moreover,using exosomes avoids many risks associated with cell transplantation.Therefore,as a novel type of cell-free therapy,MSC-exosome-mediated administration may be safer and more efficient than whole cell.In this review,we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration.In addition,we address the hypothesis of MSCs microenvironment extracellular vesicles(MSCs-MEVs)or MSCs microenvironment exosomes(MSCs-MExos)that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications.This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration. | Peng Hu Qinxin Yang Qi Wang Chenshuo Shi Dali Wang Ubaldo Armato Ilaria Dal Prà Anna Chiarini | 2019 | Burns & Trauma2019，7，1： | 20 |
| 3 | Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease显示文摘Mesenchymal stem cells(MSCs) have been used to treat patients suffering from acute myocardial infarction(AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microR NAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease(CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD. | Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu | 2016 | World Journal of Stem Cells2016，8，9： | 19 |
| 4 | Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease显示文摘Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016. | Edwin E. Reza-Zaldivar Mercedes A. Hernández-Sapiéns Yanet K. Gutiérrez-Mercado Sergio Sandoval-ávila Ulises Gomez-Pinedo Ana L. Márquez-Aguirre Estefanía Vázquez-Méndez Eduardo Padilla-Camberos Alejandro A. Canales-Aguirre | 2019 | Neural Regeneration Research2019，14，9： | 19 |
| 5 | 小鼠肝癌细胞H(22)源exosomes的制备及其免疫相关蛋白的初步研究显示文摘目的 分离提取和电镜观察小鼠肝癌细胞H22分泌的exosomes,并检测其含有的蛋白成分,为exosomes作为肿瘤疫苗提供理论依据。方法 超速分级离心和蔗糖密度梯度离心纯化得到exosomes,并经透射电镜观察鉴定,运用肽质量指纹谱质谱分析和Western blot检测exosomes含有的蛋白成分。结果 从小鼠肝癌细胞H22中提取出exosomes,直径约为20-90 nm的膜性囊泡,呈圆形或椭圆形。该exosomes含有热休克蛋白(HSP)70、ICAM-1、延伸因子G2、动力蛋白轻链A、C-myc和Vav-2蛋白。结论 超速分级离心和蔗糖密度梯度离心提取纯化exosomes的方法具有可行性,小鼠肝癌细胞H22源exosomes表达有与抗原呈递相关蛋白(HSP70、ICAM-1),迁移相关蛋白(动力蛋白轻链A),粘附相关蛋白(ICAM-1),细胞骨架相关蛋白(延伸因子G2),肿瘤相关蛋白(C-myC蛋白、Vav-2蛋白),具有免疫原性。 | 李静 沈宜 汤为学 陈黎 段红 | 2007 | 中华肝脏病杂志2007，15，6： | 17 |
| 6 | Neural stem cell transplantation therapy for brain ischemic stroke:Review and perspectives显示文摘Brain ischemic stroke is one of the most common causes of death and disability,currently has no efficient therapeutic strategy in clinic.Due to irreversible functional neurons loss and neural tissue injury,stem cell transplantation may be the most promising treatment approach.Neural stem cells(NSCs)as the special type of stem cells only exist in the nervous system,can differentiate into neurons,astrocytes,and oligodendrocytes,and have the abilities to compensate insufficient endogenous nerve cells and improve the inflammatory microenvironment of cell survival.In this review,we focused on the important role of NSCs therapy for brain ischemic stroke,mainly introduced the methods of optimizing the therapeutic efficacy of NSC transplantation,such as transfection and overexpression of specific genes,pretreatment of NSCs with inflammatory factors,and co-transplantation with cytokines.Next,we discussed the potential problems of NSC transplantation which seriously limited their rapid clinical transformation and application.Finally,we expected a new research topic in the field of stem cell research.Based on the bystander effect,exosomes derived from NSCs can overcome many of the risks and difficulties associated with cell therapy.Thus,as natural seed resource of nervous system,NSCs-based cell-free treatment is a newly therapy strategy,will play more important role in treating ischemic stroke in the future. | Gui-Long Zhang Zhi-Han Zhu Ye-Zhong Wang | 2019 | World Journal of Stem Cells2019，11，10： | 17 |
| 7 | 胰腺的癌症诊断由免费并且 exosomal miRNA显示文摘 Patients with pancreatic adenocarcinoma(PaCa) have a dismal prognosis. This is in part due to late diagnosis prohibiting surgical intervention, which provides the only curative option as PaCa are mostly chemo- and radiation resistance. Hope is raised on a reliable noninvasive/minimally invasive diagnosis that is still missing. Recently two diagnostic options are discussed, serum MicroRNA(miRNA) and serum exosomes. Serum miRNA can be free or vesicle-, particularly, exosomesenclosed. This review will provide an overview on the current state of the diagnostic trials on free serum miRNA and proceed with an introduction of exosomes that use as a diagnostic tool in serum and other body fluids has not received sufficient attention, although serum exosome miRNA in combination with protein marker expression likely will increase the diagnostic and prognostic power. By their crosstalk with host cells, which includes binding-initiated signal transduction, as well as reprogramming target cells via the transfer of proteins, mRNA and miRNA exosomes are suggested to become a most powerful therapeutics. I will discuss which hurdles have still to be taken as well as the different modalities, which can be envisaged to make therapeutic use of exosomes. PaCa are known to most intensely crosstalk with the host as apparent by desmoplasia and frequent paraneoplastic syndromes. Thus, there is hope that the therapeutic application of exosomes brings about a major breakthrough. | Margot Zller | 2013 | World Journal of Gastrointestinal Pathophysiology2013，4，4： | 15 |
| 8 | Exosomes as mediators of neuron-glia communication in neuroinflammation显示文摘In recent years,a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological conditions.These nanovesicles (30–150 nm) contain proteins,RNAs and lipids,and their internalization by bystander cells could alter their normal functions.This review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous system.Special emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain,in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative disorders.Given the small size and characteristics of exosomes,they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and neuropathologies.Finally,although the application potential of exosome is still limited,current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation. | María Pascual Francesc Ibánez Consuelo Guerri | 2020 | Neural Regeneration Research2020，15，5： | 14 |
| 9 | Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism显示文摘Periodontitis is caused by host immune-inflammatory response to bacterial insult.A high proportion of proinflammatory macrophages to anti-inflammatory macrophages leads to the pathogenesis of periodontitis.As stem cell-derived exosomes can modulate macrophage phenotype,dental pulp stem cell-derived exosomes(DPSC-Exo)can effectively treat periodontitis.In this study,we demonstrated that DPSC-Exo-incorporated chitosan hydrogel(DPSC-Exo/CS)can accelerate the healing of alveolar bone and the periodontal epithelium in mice with periodontitis.Gene Ontology(GO)term enrichment analysis showed that treatment with DPSC-Exo/CS ameliorated periodontal lesion by suppressing periodontal inflammation and modulating the immune response.Specifically,DPSC-Exo/CS facilitated macrophages to convert from a pro-inflammatory phenotype to an anti-inflammatory phenotype in the periodontium of mice with periodontitis,the mechanism of which could be associated with miR-1246 in DPSC-Exo.These results not only shed light on the therapeutic mechanism of DPSCExo/CS but also provide the basis for developing an effective therapeutic approach for periodontitis. | Zongshan Shen Shuhong Kuang Yong Zhang Mingmei Yang Wei Qin Xuetao Shi Zhengmei Lin | 2020 | Bioactive Materials2020，5，4： | 14 |
| 10 | Exosomes-the enigmatic regulators of bone homeostasis显示文摘Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells.Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury. | Minhao Gao Weiyang Gao J. M. Papadimitriou Changqing Zhang Junjie Gao Minghao Zheng | 2018 | Bone Research2018，6，4： | 13 |
| 11 | Advancing application of mesenchymal stem cell-based bone tissue regeneration显示文摘Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration. | Fengqing Shang Yang Yu Shiyu Liu Leiguo Ming Yongjie Zhang Zhifei Zhou Jiayu Zhao Yan Jin | 2021 | Bioactive Materials2021，6，3： | 13 |
| 12 | Mesenchymal stem cells from different sources and their derived exosomes: A pre-clinical perspective显示文摘Since the introduction of cell therapy as a strategy for the treatment of many diseases,mesenchymal stem cells have emerged as ideal candidates,yet the underlying mechanisms of their beneficial effects are only partially understood.At the start of the 21st century,a paracrine effect was proposed as a mechanism of tissue repair by these cells.In addition,a role was suggested for a heterogeneous population of extracellular vesicles in cell-to-cell communication.Some of these vesicles including exosomes have been isolated from most fluids and cells,as well as from supernatants of in vitro cell cultures.Recent research in the field of regenerative medicine suggests that exosomes derived from mesenchymal stem cells could be a powerful new therapeutic tool.This review examines the therapeutic potential of these exosomes obtained from the sources most used in cell therapy:bone marrow,adipose tissue,and umbilical cord. | María álvarez-Viejo | 2020 | World Journal of Stem Cells2020，12，2： | 13 |
| 13 | Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss显示文摘The differentiation shift from osteogenesis to adipogenesis of bone marrow mesenchymal stem cells(BMSCs)characterizes many pathological bone loss conditions.Stromal cell-derived factor-1(SDF1)is highly enriched in the bone marrow for C-X-C motif chemokine receptor 4(CXCR4)-positive hematopoietic stem cell(HSC)homing and tumor bone metastasis.In this study,we displayed CXCR4 on the surface of exosomes derived from genetically engineered NIH-3T3 cells.CXCR4+exosomes selectively accumulated in the bone marrow.Then,we fused CXCR4+exosomes with liposomes carrying antagomir-188 to produce hybrid nanoparticles(NPs).The hybrid NPs specifically gathered in the bone marrow and released antagomir-188,which promoted osteogenesis and inhibited adipogenesis of BMSCs and thereby reversed age-related trabecular bone loss and decreased cortical bone porosity in mice.Taken together,this study presents a novel way to obtain bone-targeted exosomes via surface display of CXCR4 and a promising anabolic therapeutic approach for age-related bone loss. | Yan Hu Xiaoqun Li Qin Zhang Zhengrong Gu Ying Luo Jiawei Guo Xiuhui Wang Yingying Jing Xiao Chen Jiacan Su | 2021 | Bioactive Materials2021，6，9： | 12 |
| 14 | Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function显示文摘Background:Diabetic wounds are one of the most common and serious complications of diabetes mellitus,characterized by the dysfunction of wound-healing-related cells in quantity and quality.Our previous studies revealed that human amniotic epithelial cells(hAECs)could promote diabetic wound healing by paracrine action.Interestingly,numerous studies demonstrated that exosomes derived from stem cells are the critical paracrine vehicles for stem cell therapy.However,whether exosomes derived from hAECs(hAECs-Exos)mediate the effects of hAECs on diabetic wound healing remains unclear.This study aimed to investigate the biological effects of hAECs-Exos on diabetic wound healing and preliminarily elucidate the underlying mechanism.Methods:hAECs-Exos were isolated by ultracentrifugation and identified by transmission electron microscopy,dynamic light scattering and flow cytometry.A series of in vitro functional analyses were performed to assess the regulatory effects of hAECs-Exos on human fibroblasts(HFBs)and human umbilical vein endothelial cells(HUVECs)in a high-glycemic microenvironment.Highthroughput sequencing and bioinformatics analyses were conducted to speculate the related mechanisms of actions of hAECs-Exos on HFBs and HUVECs.Subsequently,the role of the candidate signaling pathway of hAECs-Exos in regulating the function of HUVECs and HFBs,as well as in diabetic wound healing,was assessed.Results:hAECs-Exos presented a cup-or sphere-shaped morphology with a mean diameter of 105.89±10.36 nm,were positive for CD63 and TSG101 and could be internalized by HFBs and HUVECs.After that,hAECs-Exos not only significantly promoted the proliferation and migration of HFBs,but also facilitated the angiogenic activity of HUVECs in vitro.High-throughput sequencing revealed enriched miRNAs of hAECs-Exos involved in wound healing.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses have shown that the target genes of the top 15 miRNAs were highly enriched in the PI3K-AKT pathway.Further functional studies demonstrated that the PI3K-AKT-mTOR pathway was necessary for the induced biological effects of hAECs-Exos on HFBs and HUVECs,as well as on wound healing,in diabetic mice.Conclusions:Our findings demonstrated that hAECs-Exos represent a promising,novel strategy for diabetic wound healing by promoting angiogenesis and fibroblast function via activation of the PI3K-AKT-mTOR pathway. | Pei Wei Chenjian Zhong Xiaolan Yang Futing Shu Shichu Xiao Teng Gong Pengfei Luo Li Li Zhaohong Chen Yongjun Zheng Zhaofan Xia | 2020 | Burns & Trauma2020，8，1： | 12 |
| 15 | Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine显示文摘Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries. | Zhan-Jun Ma Jing-Jing Yang Yu-Bao Lu Zhao-Yang Liu Xue-Xi Wang | 2020 | World Journal of Stem Cells2020，12，8： | 12 |
| 16 | Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells显示文摘Sjögren’s syndrome(SS)is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands.Our previous studies showed that myeloid-derived suppressor cells(MDSCs)exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome(ESS),but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS.In this study,we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes(OE-MSC-Exos)significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels.Moreover,treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice.Mechanistically,OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs.In addition,the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling,indicating an autocrine pathway of MDSC functional modulation by IL-6.Taken together,our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs,possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases. | Ke Rui Yue Hong Qiugang Zhu Xiaofei Shi Fan Xiao Hailong Fu Qing Yin Yida Xing Xinfeng Wu Xiaodan Kong Huaxi Xu Jie Tian Shengjun Wang Liwei Lu | 2021 | Cellular & Molecular Immunology2021，18，2： | 12 |
| 17 | Exosome-functionalized magnesium-organic framework-based scaffoldswith osteogenic, angiogenic and anti-inflammatory properties foraccelerated bone regeneration显示文摘Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effectivetherapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promisingstrategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study,motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized anexosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of thebenefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhanceosteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated thebeneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bonemarrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells(HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells,stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and acceleratedbone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed thatPLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, weprovide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesisproperty. | Yue Kang Chang Xu Ling’ao Meng Xufeng Dong Min Qi Daqing Jiang | 2022 | Bioactive Materials2022，7，12： | 11 |
| 18 | Enhancement of acellular cartilage matrix scaffold by Wharton’s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration显示文摘Articular cartilage defect repair is a problem that has long plagued clinicians.Although mesenchymal stem cells(MSCs)have the potential to regenerate articular cartilage,they also have many limitations.Recent studies have found that MSC-derived exosomes(MSC-Exos)play an important role in tissue regeneration.The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix(ACECM)scaffold and to explore the underlying mechanism.The results of in vitro experiments show that human umbilical cord Wharton’s jelly MSC-Exos(hWJMSC-Exos)can promote the migration and proliferation of bone marrow-derived MSCs(BMSCs)and the proliferation of chondrocytes.We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype.The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model.This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response,which may be a promoting factor for osteochondral regeneration.In addition,microRNA(miRNA)sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage.We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis.In summary,this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. | Shuangpeng Jiang Guangzhao Tian Zhen Yang Xiang Gao Fuxin Wang Juntan Li Zhuang Tian Bo Huang Fu Wei Xinyu Sang Liuqi Shao Jian Zhou Zhenyong Wang Shuyun Liu Xiang Sui Quanyi Guo Weimin Guo Xu Li | 2021 | Bioactive Materials2021，6，9： | 11 |
| 19 | 细胞间信息交流的新载体——外泌体显示文摘外泌体(exosomes)是细胞分泌的纳米级别膜性小泡,在20世纪80年代初就已经被发现,但其在细胞间所起到的信息交流作用,直至最近才开始为人们所认知.应用大规模分析技术使得exosomes中的复杂成分不断被确定,因为其中的脂质、蛋白质和RNA成分在脂质膜的保护下具有充分的生物学活性,可有效发挥对受体细胞的调节作用,引起科学界的极大兴趣,逐渐成为研究热点之一.我们综述了近几年关于exosomes的研究成果,总结了其参与细胞间信息交流的三种主要方式,包括膜表面信号分子的直接作用、膜融合时内容物的胞内调节以及生物活性成分的释放调节.Exosomes的发现使得细胞间的信息交流更加精细和全面,尤其重要的是,它的发现揭示了存在于机体自身的RNA胞间转移途径.我们还进一步综述了exosomes的三种作用方式在神经系统及肿瘤发生发展中的作用,探讨了exosomes在疾病监测、自身免疫性疾病与缺血性疾病治疗中的临床应用价值.在基因治疗领域,由于具有安全有效的靶向运输能力,exosomes将有望成为理想的基因治疗载体. | 刘儒涛 王世伟 刘晶 | 2013 | 生物化学与生物物理进展2013，40，8： | 11 |
| 20 | Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion显示文摘BACKGROUND Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown. AIM To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells. METHODS Serum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery. HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using qPCR and dualluciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTS HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a. CONCLUSION Our findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells. | Shun-Qi Cao Hong Zheng Bao-Cun Sun Zheng-Lu Wang Tao Liu Dong-Hui Guo Zhong-Yang Shen | 2019 | World Journal of Gastroenterology2019，25，35： | 10 |
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