Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strate...Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the exist...BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.展开更多
Neurodegenerative disorders affect millions of people worldwide,and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years.While thera...Neurodegenerative disorders affect millions of people worldwide,and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years.While therapies exist to aid in symptomatic relief,effective treatments that can stop or reve rse the progress of each neurodegenerative disease are lacking.Recently,research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied.Exosomes,30-150 nm in diameter,are one type of extracellular vesicles facilitating cell-to-cell communication.Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases,such as Alzheimer's disease,Parkinson s disease,and amyotrophic lateral sclerosis.Accordingly,the exosomes derived from the patients are an invaluable source of disease biomarkers.On the other hand,exosomes,especially those derived from stem cells,could serve as a therapeutic for these disorders,as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases.This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders.We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy.Finally,this review concludes with outstanding questions that remain to be addressed in exosomal research.展开更多
Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a ...Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.展开更多
Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation...Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.展开更多
Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving mul...Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.展开更多
Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regu...Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.展开更多
The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinica...The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinical application.Tendon Stem/Progenitor Cells(TSPCs)-derived exosomes have emerged as promising cellfree therapeutic agents.Therefore,urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms.In this study,TSPC-Exos were found to promote the proliferation,migration,and expression of fibrogenesis markers in BMSCs.Furthermore,TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization.In a rat model of rotator cuff repair,TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface,the biomechanical properties of the repaired tendon,and the function of the joint.Mechanistically,TSPC-Exos exhibited high expression of miR-21a-5p,which regulated the expression of PDCD4.The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation,migration,and fibrogenesis in BMSCs.This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies,potentially benefiting patients with rotator cuff tear in the future.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investi...Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increased peritoneal thickness and higher expression ofα-SMA,collagen-I,fibronectin,and ECM1.The mice with PD showed decreased miR-27a-3p.Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment,while PF and mesothelial damage were significantly ameliorated.Additionally,markers of fibrosis(α-SMA,collagen-I,fibronectin,ECM1)and profibrotic cytokines(TGF-β1,PDGF)were downregulated at the mRNA and protein levels after BMSC-Exos treatment.In HMrSV5 cells,BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF.Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin(epithelial marker)and decreased expression ofα-SMA,Snail,and vimentin(mesenchymal markers)compared to those of the 4.25%PDF-treated cells.Importantly,a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p.TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos.Conclusion:The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.展开更多
Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheime...Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.展开更多
Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported t...Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.展开更多
Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged s...Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.展开更多
Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extra...Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins,peptides,nucleotides,and lipids secreted from their cellular sources.Increasing evidence shows that exosomes participate in a communication network in the nervous system,in which astrocyte-derived exosomes play important roles.In this review,we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system.We also discuss the potential research directions of the exosome-based communication network in the nervous system.The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain.New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.展开更多
Recent advancements in stem cell-derived exosome therapy for diabetic brain hemorrhage are discussed in this editorial,which highlights this therapy’s potential for revolutionizing diabetic brain hemorrhage treatment...Recent advancements in stem cell-derived exosome therapy for diabetic brain hemorrhage are discussed in this editorial,which highlights this therapy’s potential for revolutionizing diabetic brain hemorrhage treatment.The paper offers compelling evidence that exosomes can effectively reduce neuroinflammation and promote recovery from diabetic brain hemorrhage.Although these findings are promising,further research is warranted to fully understand the underlying mechanisms and to validate the therapeutic potential of exosomes in clinical settings.The findings of this study indicate that continued exploration should be conducted into exosome-based therapies as a novel approach to managing diabetic brain hemorrhage.展开更多
Exosomes,minute vesicles ubiquitously released by diverse cell types,serve as critical mediators in intercellular communication.Their pathophysiological relevance,especially in malignancies,has garnered significant at...Exosomes,minute vesicles ubiquitously released by diverse cell types,serve as critical mediators in intercellular communication.Their pathophysiological relevance,especially in malignancies,has garnered significant attention.A meticulous exploration of the exosomal impact on cancer development has unveiled avenues for innovative and clinically valuable techniques.The cargo conveyed by exosomes exerts transformative effects on both local and distant microenvironments,thereby influencing a broad spectrum of biological responses in recipient cells.These membranebound extracellular vesicles(EVs)play a pivotal role in delivering bioactive molecules among cells and organs.Cellular and biological processes in recipient cells,ranging from stromal cell reprogramming to immunological responses,extracellular matrix formation,and modulation of cancer cell activation,expansion,and metastasis,are subject to exosome-mediated cell-to-cell communication.Moreover,exosomes have been implicated in endowing cancer cells with resistance to treatment.Extensive research has explored the potential of exosomes as therapeutic targets and diagnostic indicators.This comprehensive review seeks to provide an in-depth understanding of the pivotal components and roles of exosomes in tumorigenesis,growth,progression,and therapeutic responses.The insights into the multifaceted involvement of exosomes in malignant cancers are essential for the scientific community,fostering the development of novel therapeutic and diagnostic strategies in the relentless pursuit of cancer.展开更多
Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is no...Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.展开更多
Exosomes,nanoscale extracellular vesicles(EVs)derived from the invagination of the endosomal membrane,are secreted by a majority of cell types.As carriers of DNA,mRNA,proteins,and microRNAs,exosomes are implicated in ...Exosomes,nanoscale extracellular vesicles(EVs)derived from the invagination of the endosomal membrane,are secreted by a majority of cell types.As carriers of DNA,mRNA,proteins,and microRNAs,exosomes are implicated in regulating biological activities under physiological and pathological conditions.Kidney-derived exosomes,which vary in origin and function,may either contribute to the pathogenesis of disease or represent a potential therapeutic resource.Membranous nephropathy(MN),an autoimmune kidney disease characterized by glomerular damage,is a predominant cause of nephrotic syndrome.Notably,MN,especially idiopathic membranous nephropathy(IMN),often results in end-stage renal disease(ESRD),affecting approximately 30%of patients and posing a considerable economic challenge to healthcare systems.Despite substantial research,therapeutic options remain ineffective at halting IMN progression,underscoring the urgent need for innovative strategies.Emerging evidence has implicated exosomes in IMN’s pathophysiology;Providing a fresh perspective for the discovery of novel biomarkers and therapeutic strategies.This review aims to scrutinize recent developments in exosome-related mechanisms in IMN and evaluate their potential as promising therapeutic targets and diagnostic biomarkers,with the hope of catalyzing further investigations into the utility of exosomes in MN,particularly IMN,ultimately contributing to improved patient outcomes in these challenging disease settings.展开更多
基金Supported by Guizhou University of Traditional Chinese Medicine Doctoral Initiation Fund,No.202306and Changshu Municipal Science and Technology Bureau Supporting Project,No.CS202030.
文摘Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
基金approved by the medical ethics committee of the authors’institution(protocol number:56733164-203-E.5863).
文摘BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.
基金supported by the National Institute on Aging of NIH(No.RF1AG072510 to HW)the National Institute of General Medical Sciences(NINGM)of NIH(No.P20GM103443 to HW via Dr.Victor Huber)+1 种基金the National Science Foundation(NSF)(No.DGE-1633213 to CCH via Dr.Brian Burrell)the NIH/NIGMS(No.T32GM-136503 to CCH via Dr.Brian Burrell)。
文摘Neurodegenerative disorders affect millions of people worldwide,and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years.While therapies exist to aid in symptomatic relief,effective treatments that can stop or reve rse the progress of each neurodegenerative disease are lacking.Recently,research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied.Exosomes,30-150 nm in diameter,are one type of extracellular vesicles facilitating cell-to-cell communication.Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases,such as Alzheimer's disease,Parkinson s disease,and amyotrophic lateral sclerosis.Accordingly,the exosomes derived from the patients are an invaluable source of disease biomarkers.On the other hand,exosomes,especially those derived from stem cells,could serve as a therapeutic for these disorders,as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases.This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders.We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy.Finally,this review concludes with outstanding questions that remain to be addressed in exosomal research.
基金supported by the National Natural Science Foundation of China (No. 82203056)Natural Science Foundation of Liaoning Province (No. 2023-BS-167)+1 种基金Science and Technology Talent Innovation Support Plan of Dalian (No. 2022RQ091)“1+X” program for Clinical Competency Enhancement–Clinical Research Incubation Project of the Second Hospital of Dalian Medical University (No. 2022LCYJYB01)。
文摘Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.
基金supported by grants for National Key Research and Development Program of China(No.2020YFA0113003)Key Research and Development Project of Zhejiang Province(No.2023C03046)+1 种基金Fundamental Research Funds for the Central Universities(No.2022ZFJH003)Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2022026C,JNL-2023003C).
文摘Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.
文摘Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)the National Natural Science Foundation of China No.81930070(to SF)+1 种基金Multi-fund Investment Key Projects,No.21JCZDJC01100(to ZW)the Tianjin Science and Technology Planning Project,No.22JRRCRC00010(to SF)。
文摘Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.
基金supported by the National Natural Science Foundation of China(Grant No.82172511,81972125 and 82172510)Shenzhen“San-Ming”Project of Medicine(No.SZSM202211019).
文摘The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinical application.Tendon Stem/Progenitor Cells(TSPCs)-derived exosomes have emerged as promising cellfree therapeutic agents.Therefore,urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms.In this study,TSPC-Exos were found to promote the proliferation,migration,and expression of fibrogenesis markers in BMSCs.Furthermore,TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization.In a rat model of rotator cuff repair,TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface,the biomechanical properties of the repaired tendon,and the function of the joint.Mechanistically,TSPC-Exos exhibited high expression of miR-21a-5p,which regulated the expression of PDCD4.The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation,migration,and fibrogenesis in BMSCs.This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies,potentially benefiting patients with rotator cuff tear in the future.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金supported by the Technology Development Program of Shanghai Pudong New District(No.PKJ2021-Y34)the Excellent Young Medical Talent Training Program of Pudong Health Commission of Shanghai(No.PWRq2022-18).
文摘Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increased peritoneal thickness and higher expression ofα-SMA,collagen-I,fibronectin,and ECM1.The mice with PD showed decreased miR-27a-3p.Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment,while PF and mesothelial damage were significantly ameliorated.Additionally,markers of fibrosis(α-SMA,collagen-I,fibronectin,ECM1)and profibrotic cytokines(TGF-β1,PDGF)were downregulated at the mRNA and protein levels after BMSC-Exos treatment.In HMrSV5 cells,BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF.Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin(epithelial marker)and decreased expression ofα-SMA,Snail,and vimentin(mesenchymal markers)compared to those of the 4.25%PDF-treated cells.Importantly,a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p.TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos.Conclusion:The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.
基金supported by the National Natural Science Foundation of China,Nos.82171194 and 81974155(both to JL)the Shanghai Municipal Science and Technology Commission Medical Guide Project,No.16411969200(to WZ)Shanghai Municipal Science and Technology Commission Biomedical Science and Technology Project,No.22S31902600(to JL)。
文摘Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.
基金supported by the National Natural Science Foundation of China,No.81870975(to SZ)。
文摘Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.
文摘Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.
基金supported by the National Natural Science Foundation of China,No.82071278(to PY)Outstanding Young Medical Talents Project of Changhai Hospital,No.2021JCSQ03(to PY)+1 种基金Shanghai Sailing Program,No.20YF1448000(to XZ)Medical Health Science and Technology Project of Zhoushan City,No.2022JRC01(to HL).
文摘Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins,peptides,nucleotides,and lipids secreted from their cellular sources.Increasing evidence shows that exosomes participate in a communication network in the nervous system,in which astrocyte-derived exosomes play important roles.In this review,we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system.We also discuss the potential research directions of the exosome-based communication network in the nervous system.The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain.New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.
文摘Recent advancements in stem cell-derived exosome therapy for diabetic brain hemorrhage are discussed in this editorial,which highlights this therapy’s potential for revolutionizing diabetic brain hemorrhage treatment.The paper offers compelling evidence that exosomes can effectively reduce neuroinflammation and promote recovery from diabetic brain hemorrhage.Although these findings are promising,further research is warranted to fully understand the underlying mechanisms and to validate the therapeutic potential of exosomes in clinical settings.The findings of this study indicate that continued exploration should be conducted into exosome-based therapies as a novel approach to managing diabetic brain hemorrhage.
文摘Exosomes,minute vesicles ubiquitously released by diverse cell types,serve as critical mediators in intercellular communication.Their pathophysiological relevance,especially in malignancies,has garnered significant attention.A meticulous exploration of the exosomal impact on cancer development has unveiled avenues for innovative and clinically valuable techniques.The cargo conveyed by exosomes exerts transformative effects on both local and distant microenvironments,thereby influencing a broad spectrum of biological responses in recipient cells.These membranebound extracellular vesicles(EVs)play a pivotal role in delivering bioactive molecules among cells and organs.Cellular and biological processes in recipient cells,ranging from stromal cell reprogramming to immunological responses,extracellular matrix formation,and modulation of cancer cell activation,expansion,and metastasis,are subject to exosome-mediated cell-to-cell communication.Moreover,exosomes have been implicated in endowing cancer cells with resistance to treatment.Extensive research has explored the potential of exosomes as therapeutic targets and diagnostic indicators.This comprehensive review seeks to provide an in-depth understanding of the pivotal components and roles of exosomes in tumorigenesis,growth,progression,and therapeutic responses.The insights into the multifaceted involvement of exosomes in malignant cancers are essential for the scientific community,fostering the development of novel therapeutic and diagnostic strategies in the relentless pursuit of cancer.
基金supported by the National Natural Science Foundation of China(No.82070859).
文摘Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.
基金supported by grants from the National Key Research and Development Program(Grant No.2019YFC1709404)the Science and Technology Department of Shaanxi Province(Grant No.2021LCZX-13).
文摘Exosomes,nanoscale extracellular vesicles(EVs)derived from the invagination of the endosomal membrane,are secreted by a majority of cell types.As carriers of DNA,mRNA,proteins,and microRNAs,exosomes are implicated in regulating biological activities under physiological and pathological conditions.Kidney-derived exosomes,which vary in origin and function,may either contribute to the pathogenesis of disease or represent a potential therapeutic resource.Membranous nephropathy(MN),an autoimmune kidney disease characterized by glomerular damage,is a predominant cause of nephrotic syndrome.Notably,MN,especially idiopathic membranous nephropathy(IMN),often results in end-stage renal disease(ESRD),affecting approximately 30%of patients and posing a considerable economic challenge to healthcare systems.Despite substantial research,therapeutic options remain ineffective at halting IMN progression,underscoring the urgent need for innovative strategies.Emerging evidence has implicated exosomes in IMN’s pathophysiology;Providing a fresh perspective for the discovery of novel biomarkers and therapeutic strategies.This review aims to scrutinize recent developments in exosome-related mechanisms in IMN and evaluate their potential as promising therapeutic targets and diagnostic biomarkers,with the hope of catalyzing further investigations into the utility of exosomes in MN,particularly IMN,ultimately contributing to improved patient outcomes in these challenging disease settings.
