Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment.Exosomes are co...Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment.Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting.More researches and future developments are needed,although exosome-based therapies need further research and development before they can be translated into clinical applications.In this review,we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell(MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential,advantages,disadvantages and also other comprehensive details.In vitro,in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed.We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer.In the meantime,we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies,focusing on their role in cancer treatment,particularly for pancreatic cancer.By examining current findings,this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.展开更多
Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“me...Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.展开更多
Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.E...Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.展开更多
Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promi...Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine func...We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.展开更多
In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology.They explored an innovative approach to enhancing gemcitabine(GEM)delivery an...In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology.They explored an innovative approach to enhancing gemcitabine(GEM)delivery and efficacy using human bone marrow mesenchymal stem cells(HU-BMSCs)-derived exosomes.The manufacture of GEM-loaded HU-BMSCs-derived exosomes(Exo-GEM)has been optimized.The Tang et al’s study demonstrated that Exo-GEM exhibits enhanced cytotoxicity and apoptosis-inducing effects compared to free GEM,highlighting the potential of exosome-based drug delivery systems as a more effective and targeted approach to chemotherapy in pancreatic cancer.Additional in vivo studies are required to confirm the safety and effectiveness of Exo-GEM before it can be considered for clinical use.展开更多
Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py ...Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.展开更多
In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
The treatment of skin wounds,especially chronic wounds,remains a critical clinical challenge and places a heavy burden on patients and healthcare systems.In recent years,the engineering strategy of using biomaterial-a...The treatment of skin wounds,especially chronic wounds,remains a critical clinical challenge and places a heavy burden on patients and healthcare systems.In recent years,the engineering strategy of using biomaterial-assisted exosomes has emerged as a powerful tool for skin repair.Compared to treatments such as debridement and regular dressing changes,the design of biomaterial-assisted exosomes not only maintains the bioactivity of exosomes at the wound site but also provides an appropriate microenvironment for the repair of complex tissues,thereby accelerating wound healing.This review systematically introduces the general characteristics of exosomes and their functions in skin wound healing,highlights recent advances in classification of natural exosomes and engineering methods which enriching their functions in intercellular communication.Then,various emerging and innovative approaches based on biomaterials delivery of exosomes are comprehensively discussed.The review seeks to bring an in-depth understanding of bioactive dressings based on exosomes therapeutic strategies,aiming to facilitate new clinical application value.展开更多
Ovarian cancer ranks as the deadliest malignancy among female reproductive system cancers,posing a significant threat to women’s health.Around seven out of ten patients are diagnosed only after reaching progressive d...Ovarian cancer ranks as the deadliest malignancy among female reproductive system cancers,posing a significant threat to women’s health.Around seven out of ten patients are diagnosed only after reaching progressive disease phases,a phenomenon closely linked to three key factors:the disease’s hidden onset location,lack of early symptoms,and absence of reliable early diagnostic methods.Therefore,identifying early diagnostic biomarkers and therapeutic targets is critical.Exosomes participate in various phases of ovarian tumorigenesis,including transforming normal cells into cancerous cells,immune regulation,invasion,metastasis,drug resistance,and angiogenesis,making them promising biomarkers for early ovarian cancer detection.This review summarizes current research on exosomal long non-coding RNAs(lncRNAs),miRNAs,and related proteins in ovarian cancer diagnosis.Exosome-based biomarkers have shown potential advantages,including high sensitivity,specificity,stability,and non-invasive accessibility.The study concludes that while exosomes hold significant diagnostic potential for ovarian cancer,additional investigations are required to standardize detection methods,validate clinical applicability,and elucidate underlying molecular mechanisms.展开更多
Exosomes(EXOs)play an important role in the progression of breast cancer.EXOs,with a diameter of approximately 100 nm,have a simple structure but diverse functions,and can affect the development of breast cancer throu...Exosomes(EXOs)play an important role in the progression of breast cancer.EXOs,with a diameter of approximately 100 nm,have a simple structure but diverse functions,and can affect the development of breast cancer through signal transduction and molecular transfer,etc.Angiogenesis provides nutrients for the growth and metastasis of breast cancer and is a crucial part of tumor progression.The mechanism of tumor angiogenesis is complex.The VEGF/VEGFR pathway promotes angiogenesis by regulating the activities of ECs.Hypoxia,a common feature in the tumor microenvironment,as a key regulator,can affect angiogenesis in multiple aspects such as the transfer of miRNAs in EXOs,protein transport,extracellular matrix regulation,and metabolic adaptation.The Notch pathway has a bidirectional regulatory role in breast cancer angiogenesis,and different molecules can promote or inhibit angiogenesis.EXOs secreted by breast cancer cells are rich in angiogenic factors.Components such as proteins and nucleic acids in EXOs can affect the functions and behaviors of vascular ECs,thereby influencing breast cancer angiogenesis.Research on the mechanisms of EXOs in breast cancer angiogenesis is of great significance for tumor treatment.EXOs are expected to become biomarkers for breast cancer diagnosis/prognosis.This research provides potential targets for in-depth understanding of the biological characteristics of breast cancer and the development of new treatment strategies.展开更多
BACKGROUND Exosome-based therapies represent a promising approach for hair regeneration.Unlike conventional treatments such as minoxidil and finasteride,exosomes deliver bioactive cargo that can stimulate dermal papil...BACKGROUND Exosome-based therapies represent a promising approach for hair regeneration.Unlike conventional treatments such as minoxidil and finasteride,exosomes deliver bioactive cargo that can stimulate dermal papilla cells,enhance angiogenesis,and modulate inflammatory pathways.However,variability in exosome sources,isolation techniques,and dosing protocols limits their clinical translation.AIM To synthesize findings from in vitro,preclinical and clinical studies,and to evaluate the efficacy,mechanisms,and challenges associated with exosome-based hair restoration therapies.METHODS A literature search was conducted using multiple databases(PubMed/Medline,Embase,Scopus,and Web of Science)employing terms for exosomes and hair regeneration for articles published in English to February 2025,following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.RESULTS A total of 27 studies(three in vitro,three pre-clinical,18 with both in vitro and preclinical component and three clinical)met the pre-defined search and inclusion criteria and were included in this review.CONCLUSION Exosome-based therapies hold immense promise for hair regeneration by leveraging their ability to modulate key signaling pathways and enhance hair follicle regeneration.While in vitro and preclinical studies demonstrate consistent efficacy across diverse exosome sources,methodological heterogeneity and a limited number of clinical studies warrant further clinical research to realize their full clinical potential for hair regeneration.展开更多
Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of ...Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of sepsis through modulating immune responses,metabolic reprogramming,coagulopathy,and organ dysfunction.This review highlights the emerging significance of exosomes in these processes.Initially,it provides an in-depth insight into exosome biogenesis and characterization,laying the groundwork for understanding their diverse and intricate functions.Subsequently,it explores the regulatory roles of exosomes in various immune cells such as neutrophils,macrophages,dendritic cells,T cells,and B cells.This analysis elucidates how exosomes are pivotal in modulating immune responses,thus contributing to the complexity of sepsis pathophysiology.Additionally,this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis.It also establishes a connection between exosomes and the coagulation cascade,which affects endothelial integrity and promotes thrombogenesis in sepsis.Moreover,the review discusses the dual role of exosomes in the progression and resolution of sepsis,exploring their complex involvement in inflammation and healing processes.Furthermore,it underscores their potential as biomarkers and therapeutic targets.Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis,emphasizing the therapeutic promise of exosome research in critical care settings.展开更多
BACKGROUND Burn wound management is challenging,and while mesenchymal stem cellderived exosomes show therapeutic potential,optimal delivery methods are unclear.AIM To study chitosan(CS)-αβ-glycerophosphate(CS-αβ-G...BACKGROUND Burn wound management is challenging,and while mesenchymal stem cellderived exosomes show therapeutic potential,optimal delivery methods are unclear.AIM To study chitosan(CS)-αβ-glycerophosphate(CS-αβ-GP)hydrogel crosslinked with adipose-derived stem cell exosomes(ASC-Exos)for healing deep burn injuries.METHODS Rats with deep burn injuries were divided into the CS+ASCs-Exos group,the ASCs-Exos group,the CS group,and the control group.The healing rates on days 4,7,and 14 after treatment were analyzed using ImageJ software.On day 14,the tissues were stained with hematoxylin and eosin staining,Masson’s trichrome staining,and immunohistochemical analysis to evaluate tumor necrosis factorα,interleukin-6(IL-6),IL-1α,IL-10,transforming growth factorβ,and epidermal growth factor.The mRNA levels of IL-1α,CD86,C-C motif chemokine ligand 22,and CD163 were evaluated through quantitative polymerase chain reaction.RESULTS The CS+ASC-Exos group exhibited enhanced healing,reduced lymphocyte infiltration,blood vessels,and muscle fiber distribution.Increased IL-10,transforming growth factorβ,and epidermal growth factor and decreased tumor necrosis factorα,IL-1α,and IL-6 expression were observed.Quantitative polymerase chain reaction revealed reduced IL-1αand CD86 and increased C-C motif chemokine ligand 22 and CD163 expression.Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factorκB(NF-κB)pathway.ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation,wound healing promotion,and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone.CONCLUSION Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds.It has anti-inflammatory effects,promotes wound healing,and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.展开更多
Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival.Mesenchymal stem cells(MSCs)have the potential to en...Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival.Mesenchymal stem cells(MSCs)have the potential to enhance renal function by suppressing the expression of cell cycle inhibitors and reducing the expression of senescence markers and microRNAs via paracrine and endocrine mechanisms.MSC-derived exosomes can alleviate AKI symptoms by regulating DNA damage,apoptosis,and other related signaling pathways through the delivery of proteins,microRNAs,long-chain noncoding RNAs,and circular RNAs.This technique is both safe and effective.MSC-derived exosomes may have great application prospects in the treatment of AKI.Understanding the underlying mechanisms will foster the development of new and promising therapeutic strategies against AKI.This review focused on recent advancements in the role of MSCs in AKI repair as well as the mechanisms underlying the role of MSCs and their secreted exosomes.It is anticipated that novel and profound insights into the functionality of MSCs and their derived exosomes will emerge.展开更多
Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture...Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.展开更多
The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options.Adipose-derived stem cell exosomes(ADSC-Exos)are promising for their capabi...The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options.Adipose-derived stem cell exosomes(ADSC-Exos)are promising for their capabilities to enhance angiogenesis,mitigate oxidative stress,modulate inflammatory pathways,support skin cell regeneration,and promote epithelialization.These exosomes deliver noncoding RNAs,including microRNAs,long non-coding RNAs,and circular RNAs,which facilitate collagen remodeling,reduce scar formation,and expedite wound healing.This study reviews the mechanisms,therapeutic roles,and challenges of non-coding RNA-loaded ADSC-Exos in wound healing and identifies critical directions for future research.It aims to provide insights for researchers into the potential mechanisms and clinical applications of ADSC-Exos non-coding RNAs in wound healing.展开更多
文摘Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment.Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting.More researches and future developments are needed,although exosome-based therapies need further research and development before they can be translated into clinical applications.In this review,we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell(MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential,advantages,disadvantages and also other comprehensive details.In vitro,in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed.We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer.In the meantime,we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies,focusing on their role in cancer treatment,particularly for pancreatic cancer.By examining current findings,this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.
文摘Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.
基金supported by the National Natural Science Foundation of China,Nos.82071291(to YY),82301464(to HM)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)+2 种基金a grant from Department of Science and Technology of Jilin Province,Nos.YDZJ202302CXJD061(to YY),20220303002SF(to YY)a grant from Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY)Talent Reserve Program of First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)。
文摘Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
基金Supported by the National Natural Science Foundation of China,No.82072537the General Project of Hunan Natural Science Foundation,No.2022JJ30412 and No.2021JJ30464.
文摘Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金supported by the National Natural Science Foundation of China,No.81801907(to NC)Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research,No.ZDSYS20230626091402006(to NC)+2 种基金Sanming Project of Medicine in Shenzhen,No.SZSM201911002(to SL)Foundation of Shenzhen Committee for Science and Technology Innovation,Nos.JCYJ20230807110310021(to NC),JCYJ20230807110259002(to JL)Science and Technology Program of Guangzhou,No.2024A04J4716(to TL)。
文摘We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.
基金Supported by the grants of China Medical University Hospital,No.DMR-112-173 and No.DMR-113-089the grant from Tungs’Taichung Metro Harbor Hospital,No.TTMHH-R1120013.
文摘In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology.They explored an innovative approach to enhancing gemcitabine(GEM)delivery and efficacy using human bone marrow mesenchymal stem cells(HU-BMSCs)-derived exosomes.The manufacture of GEM-loaded HU-BMSCs-derived exosomes(Exo-GEM)has been optimized.The Tang et al’s study demonstrated that Exo-GEM exhibits enhanced cytotoxicity and apoptosis-inducing effects compared to free GEM,highlighting the potential of exosome-based drug delivery systems as a more effective and targeted approach to chemotherapy in pancreatic cancer.Additional in vivo studies are required to confirm the safety and effectiveness of Exo-GEM before it can be considered for clinical use.
基金Supported by the National Natural Science Foundation of China(82371373,W2412120)the Shanghai Natural Science Foundation(21ZR1436100).
文摘Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
基金financially supported by the National Natural Science Foundation of China(No.82030056)Postdoctoral Innovation Talents Support Program of China(No.BX20230489)。
文摘The treatment of skin wounds,especially chronic wounds,remains a critical clinical challenge and places a heavy burden on patients and healthcare systems.In recent years,the engineering strategy of using biomaterial-assisted exosomes has emerged as a powerful tool for skin repair.Compared to treatments such as debridement and regular dressing changes,the design of biomaterial-assisted exosomes not only maintains the bioactivity of exosomes at the wound site but also provides an appropriate microenvironment for the repair of complex tissues,thereby accelerating wound healing.This review systematically introduces the general characteristics of exosomes and their functions in skin wound healing,highlights recent advances in classification of natural exosomes and engineering methods which enriching their functions in intercellular communication.Then,various emerging and innovative approaches based on biomaterials delivery of exosomes are comprehensively discussed.The review seeks to bring an in-depth understanding of bioactive dressings based on exosomes therapeutic strategies,aiming to facilitate new clinical application value.
文摘Ovarian cancer ranks as the deadliest malignancy among female reproductive system cancers,posing a significant threat to women’s health.Around seven out of ten patients are diagnosed only after reaching progressive disease phases,a phenomenon closely linked to three key factors:the disease’s hidden onset location,lack of early symptoms,and absence of reliable early diagnostic methods.Therefore,identifying early diagnostic biomarkers and therapeutic targets is critical.Exosomes participate in various phases of ovarian tumorigenesis,including transforming normal cells into cancerous cells,immune regulation,invasion,metastasis,drug resistance,and angiogenesis,making them promising biomarkers for early ovarian cancer detection.This review summarizes current research on exosomal long non-coding RNAs(lncRNAs),miRNAs,and related proteins in ovarian cancer diagnosis.Exosome-based biomarkers have shown potential advantages,including high sensitivity,specificity,stability,and non-invasive accessibility.The study concludes that while exosomes hold significant diagnostic potential for ovarian cancer,additional investigations are required to standardize detection methods,validate clinical applicability,and elucidate underlying molecular mechanisms.
文摘Exosomes(EXOs)play an important role in the progression of breast cancer.EXOs,with a diameter of approximately 100 nm,have a simple structure but diverse functions,and can affect the development of breast cancer through signal transduction and molecular transfer,etc.Angiogenesis provides nutrients for the growth and metastasis of breast cancer and is a crucial part of tumor progression.The mechanism of tumor angiogenesis is complex.The VEGF/VEGFR pathway promotes angiogenesis by regulating the activities of ECs.Hypoxia,a common feature in the tumor microenvironment,as a key regulator,can affect angiogenesis in multiple aspects such as the transfer of miRNAs in EXOs,protein transport,extracellular matrix regulation,and metabolic adaptation.The Notch pathway has a bidirectional regulatory role in breast cancer angiogenesis,and different molecules can promote or inhibit angiogenesis.EXOs secreted by breast cancer cells are rich in angiogenic factors.Components such as proteins and nucleic acids in EXOs can affect the functions and behaviors of vascular ECs,thereby influencing breast cancer angiogenesis.Research on the mechanisms of EXOs in breast cancer angiogenesis is of great significance for tumor treatment.EXOs are expected to become biomarkers for breast cancer diagnosis/prognosis.This research provides potential targets for in-depth understanding of the biological characteristics of breast cancer and the development of new treatment strategies.
文摘BACKGROUND Exosome-based therapies represent a promising approach for hair regeneration.Unlike conventional treatments such as minoxidil and finasteride,exosomes deliver bioactive cargo that can stimulate dermal papilla cells,enhance angiogenesis,and modulate inflammatory pathways.However,variability in exosome sources,isolation techniques,and dosing protocols limits their clinical translation.AIM To synthesize findings from in vitro,preclinical and clinical studies,and to evaluate the efficacy,mechanisms,and challenges associated with exosome-based hair restoration therapies.METHODS A literature search was conducted using multiple databases(PubMed/Medline,Embase,Scopus,and Web of Science)employing terms for exosomes and hair regeneration for articles published in English to February 2025,following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.RESULTS A total of 27 studies(three in vitro,three pre-clinical,18 with both in vitro and preclinical component and three clinical)met the pre-defined search and inclusion criteria and were included in this review.CONCLUSION Exosome-based therapies hold immense promise for hair regeneration by leveraging their ability to modulate key signaling pathways and enhance hair follicle regeneration.While in vitro and preclinical studies demonstrate consistent efficacy across diverse exosome sources,methodological heterogeneity and a limited number of clinical studies warrant further clinical research to realize their full clinical potential for hair regeneration.
基金USA National Institutes of Health Grant(R01-HL-139547,to JF)USA VA Grants(1I01BX004838 and IK6BX004211,to JF)+1 种基金National Natural Science Foundation of China(82002087,to TG)Shenzhen Science and Technology Program(JCYJ20210324134602008,to TG)。
文摘Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of sepsis through modulating immune responses,metabolic reprogramming,coagulopathy,and organ dysfunction.This review highlights the emerging significance of exosomes in these processes.Initially,it provides an in-depth insight into exosome biogenesis and characterization,laying the groundwork for understanding their diverse and intricate functions.Subsequently,it explores the regulatory roles of exosomes in various immune cells such as neutrophils,macrophages,dendritic cells,T cells,and B cells.This analysis elucidates how exosomes are pivotal in modulating immune responses,thus contributing to the complexity of sepsis pathophysiology.Additionally,this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis.It also establishes a connection between exosomes and the coagulation cascade,which affects endothelial integrity and promotes thrombogenesis in sepsis.Moreover,the review discusses the dual role of exosomes in the progression and resolution of sepsis,exploring their complex involvement in inflammation and healing processes.Furthermore,it underscores their potential as biomarkers and therapeutic targets.Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis,emphasizing the therapeutic promise of exosome research in critical care settings.
基金the Incubation Program of the General Hospital of the Western Theater Command,No.2021-XZYG-C29 and No.2021-XZYG-B32.
文摘BACKGROUND Burn wound management is challenging,and while mesenchymal stem cellderived exosomes show therapeutic potential,optimal delivery methods are unclear.AIM To study chitosan(CS)-αβ-glycerophosphate(CS-αβ-GP)hydrogel crosslinked with adipose-derived stem cell exosomes(ASC-Exos)for healing deep burn injuries.METHODS Rats with deep burn injuries were divided into the CS+ASCs-Exos group,the ASCs-Exos group,the CS group,and the control group.The healing rates on days 4,7,and 14 after treatment were analyzed using ImageJ software.On day 14,the tissues were stained with hematoxylin and eosin staining,Masson’s trichrome staining,and immunohistochemical analysis to evaluate tumor necrosis factorα,interleukin-6(IL-6),IL-1α,IL-10,transforming growth factorβ,and epidermal growth factor.The mRNA levels of IL-1α,CD86,C-C motif chemokine ligand 22,and CD163 were evaluated through quantitative polymerase chain reaction.RESULTS The CS+ASC-Exos group exhibited enhanced healing,reduced lymphocyte infiltration,blood vessels,and muscle fiber distribution.Increased IL-10,transforming growth factorβ,and epidermal growth factor and decreased tumor necrosis factorα,IL-1α,and IL-6 expression were observed.Quantitative polymerase chain reaction revealed reduced IL-1αand CD86 and increased C-C motif chemokine ligand 22 and CD163 expression.Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factorκB(NF-κB)pathway.ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation,wound healing promotion,and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone.CONCLUSION Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds.It has anti-inflammatory effects,promotes wound healing,and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.
文摘Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival.Mesenchymal stem cells(MSCs)have the potential to enhance renal function by suppressing the expression of cell cycle inhibitors and reducing the expression of senescence markers and microRNAs via paracrine and endocrine mechanisms.MSC-derived exosomes can alleviate AKI symptoms by regulating DNA damage,apoptosis,and other related signaling pathways through the delivery of proteins,microRNAs,long-chain noncoding RNAs,and circular RNAs.This technique is both safe and effective.MSC-derived exosomes may have great application prospects in the treatment of AKI.Understanding the underlying mechanisms will foster the development of new and promising therapeutic strategies against AKI.This review focused on recent advancements in the role of MSCs in AKI repair as well as the mechanisms underlying the role of MSCs and their secreted exosomes.It is anticipated that novel and profound insights into the functionality of MSCs and their derived exosomes will emerge.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.
基金Supported by the Intra-Hospital Project of No.940 Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army,No.2021yxky016.
文摘The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options.Adipose-derived stem cell exosomes(ADSC-Exos)are promising for their capabilities to enhance angiogenesis,mitigate oxidative stress,modulate inflammatory pathways,support skin cell regeneration,and promote epithelialization.These exosomes deliver noncoding RNAs,including microRNAs,long non-coding RNAs,and circular RNAs,which facilitate collagen remodeling,reduce scar formation,and expedite wound healing.This study reviews the mechanisms,therapeutic roles,and challenges of non-coding RNA-loaded ADSC-Exos in wound healing and identifies critical directions for future research.It aims to provide insights for researchers into the potential mechanisms and clinical applications of ADSC-Exos non-coding RNAs in wound healing.
