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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection. The development of sepsis is accompanied by the secretion of exosomes by a variety of cells, including non-coding RNA, metabolic small molecules and proteins, which play an important role in immune inflammatory response, oxidative stress, and coagulation dysfunction. The rapid development of new detection technologies has promoted the application of exosomes in the early warning, severity stratification, treatment effect and prognosis evaluation of sepsis. This article reviews the new detection technology of exosomes, the involvement of exosomes in the pathological progress of sepsis, and the latest progress in the early diagnosis, disease assessment and treatment of sepsis, in order to provide new ideas for the diagnosis and treatment of sepsis.
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Objective:To investigate the effect of bone mesenchymal stem cells derived exosomes (BMSC-Exo) on improving hippocampal microangiogenesis, energy metabolism, and behaviors in depression mouse models.Methods:(1) Mouse bone marrow mesenchymal stem cells were isolated and cultured to extract BMSC-Exo; BMSC-Exo morphology was observed by transmission electron microscopy, BMSC-Exo particle diameter ranges were determined by Zetaview analyzer, and expressions of CD9 and CD63 in BMSC-Exo were detected by Western blotting. (2) Depression models were established in 2 mice by chronic unforeseeable mild stress (CUMS); 24 h after stereotaxic injection of phosphate buffer solution (PBS) or DiR labeled BMSC-Exo, BMSC-Exo uptake was detected by in vivo imaging system. (3) Thirty-six mice were randomly divided into control group, model group and BMSC-Exo group ( n=12); CUMS was used to establish depression models in the latter 2 groups; brain stereotaxic injection of 1 μL BMSC-Exo was given to mice in the BMSC-Exo group after modeling, and same amount of PBS was given to the control group; behaviors were observed by forced swimming test (FST), tail suspension test (TST) and open field test (OFT); hippocampal microvascular length and number were detected by alkaline phosphatase staining; energy metabolism in the hippocampus was detected by micro positron emission tomography/computed tomography (mPET/CT); glucose transporter 1 (GLUT1) expression in the hippocampus was detected by Western blotting. Results:(1) BMSC-Exo had a typical disk-like vesicle-like structure with particle size of (100.5±1.4) nm; Western blotting confirmed that CD9 and CD63 expressed in BMSC-Exo. (2) In vivo imaging showed no fluorescence in the brain and liver after PBS injection, but obvious local fluorescence after BMSC-Exo injection. (3) Compared with the control group, the model group and BMSC-Exo group had significantly longer rest time in FST and TST and shorter movement distance and time in the central region of OFT ( P<0.05); compared with the model group, BMSC-Exo group had significantly shorter rest time in FST and TST and longer movement distance and time in the central region of OFT ( P<0.05). Compared with the control group, the model group and BMSC-Exo group had significantly decreased standard uptake value (SUV) of regions of interest, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05); compared with the model group, the BMSC-Exo group had significantly higher SUV, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05). Positive correlations were noted between hippocampal microvascular length and SUV and between microvascular number and SUV in the 3 groups ( r=0.540, P<0.001; r=0.600, P<0.001). Conclusion:BMSC-Exo could promote microangiogenesis energy metabolism in the hippocampus to improve depression-like behaviors in depression mouse models.
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Microneedles can penetrate the skin barrier to deliver drugs without touching the nociceptive nerves， to effectively increase the efficiency of transdermal drug delivery and improve patient compliance. Exosomes have multiple physiological functions and good biocompatibility， and are natural nanoscale drug carriers. This paper reviews the pathways and advantages of exosomes combined with microneedles for the treatment of diseases， and describes the current research status of exosome microneedle drug delivery system in various diseases. Exosome microneedles can be divided into two categories： （1） exosomes as therapeutic agents， their unique physiological origin can effectively avoid the toxicity and immunogenicity of conventional drugs and other problems； combined with microneedles directly in the specific medication site can greatly improve the metabolic consumption of oral drug delivery and patient compliance of injection drug delivery. （2） Exosomes as drug carriers， their natural vesicle structure and endogenous characteristics can protect the metabolism of foreign drugs in the body and enhance the targeting； combined with microneedles can effectively solve the problem of transdermal delivery of drugs with high efficacy but poor stability. Exosome microneedle drug delivery system is still in the laboratory stage， but it has shown great development prospects in repairing spinal cord injury， promoting diabetic ulcer wound healing， germinating， intervening myocardial infraction， relieving chronic pain and other diseases.
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Immunosuppressant is one of the main preventive measures for rejection after organ transplantation, whereas it may reduce the host response capability to pathogens and increase the risk of infection. In recent years, the application of mesenchymal stem cell (MSC) therapy in the field of solid organ transplantation has attracted widespread attention. Preclinical studies have shown that MSC therapy may prolong the survival time of transplant kidney, induce immune tolerance, accelerate the repair of acute kidney injury and promote the recovery of renal function. Clinical trials have confirmed the safety, tolerance and effectiveness of MSC therapy. Consequently, general characteristics, immunomodulation and tissue repair function of MSC, and the application of MSC in clinical trials of kidney transplantation were reviewed, the unresolved issues were briefly discussed and the prospects for subsequent research were predicted, aiming to provide reference for promoting the application of MSC therapy in clinical kidney transplantation.
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@#Objective To isolate,purify and identify exosomes secreted by mouse primary peritoneal macrophages.Methods Five male C57BL/6 mice were intraperitoneally injected with 3% mercaptoacetate broth respectively,and the primary peritoneal macrophages were obtained by lavage,and then the purity was analyzed by flow cytometry.The exosomes of mouse primary peritoneal macrophages were extracted by ExoQuick TC exosome kit,which were measured for the protein content with BCA kit,observed for the morphology by transmission electron microscopy,detected for the particle size and distribution with nanoparticle tracking analyzer,and determined for the expression of exosome-specific markers(CD9,CD63 and TSG101) by Western blot.Results About 5 × 10~6 peritoneal macrophages with the purity of(99.17±0.65)%were obtained from each mouse.Approximately 869 μg of exosomal protein was extracted from 5 mL of mouse primary peritoneal macrophage culture supernatant.The exosomes of mouse primary peritoneal macrophages were typical tea saucerlike vesicles with strong refraction under electron microscopy,and highly expressed the exosome-specific markers TSG101,CD63 and CD9.The particle size distribution was concentrated between 100 and 200 nm,with an average particle size of175.2 nm.Conclusion Intraperitoneal injection of mercaptoacetate broth can improve the yield of mouse primary peritoneal macrophages.ExoQuick TC.exosome kit can extract sufficient amount of exosomes with high purity from mouse primary peritoneal macrophages.
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Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.
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Objective To compare and analyze the gene mutation of EGFR of bronchoalveolar lavage fluid(BALF)exosome,serum and lung cancer tissue specimens of patients with advanced non-small cell lung cancer(NSCLC)and assess whether the BALF exosome specimens are suitable for screening before clinical targeted therapy,to provide new ideas and screening methods for early individualized treatment of advanced NSCLC patients.Methods BALF exosomes,serum and lung cancer tissue specimens EGFR gene mutations of 78 cases with advanced NSCLC were detected by using amplification refractory mutation system(ARMS)method in Department of Respiratory and Critical Care Medicine in our hospital from May 2021 to May 2023,and the results were retrospec-tively analyzed.A comparative analysis of the specimens was conducted using lung cancer tissue specimens as bench-marks.Results A total of 33,25 and 38 cases of EGFR gene mutation and 42,53 and 40 cases of EGFR wild type were detected in BALF exosomes,serum and lung cancer tissues specimens respectively.The mutation rate of EGFR gene was 42.3%(33/78,32.1%(25/78)and 48.7%(38/78)in BALF exosomes,serum and lung cancer tissues specimens respectively.EGFR detection showed no results in 3 cases and the false-negative rate was 6.4%(5/78)in BALF specimen,and false-negative rate was 16.7%(13/78)in serum.The detection coincidence rate of EGFR mutation was 86.8%(33/38)in BALF exosomes specimen,and 65.8%(25/38)in serum.Conclusions EGFR gene mutation rate in BALF exosome specimen is consistent with that in serum and lung cancer tissue samples,showing no statistical significance(P>0.05).It is superior to serum specimen and suitable for patient screening before targeted therapy and provides new ideas and screening methods for early individualized treatment decisions of advanced NSCLC patients.
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BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.
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BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.
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BACKGROUND:Endothelin has been found to be involved in the breakdown of the blood-spinal cord barrier after spinal cord injury,and stem cell-derived exosomes can reduce the permeability of the blood-spinal cord barrier and repair spinal cord injury. OBJECTIVE:To investigate whether exosomes produced by human umbilical cord mesenchymal stem cells can reduce the permeability of the blood-spinal cord barrier by inhibiting endothelin-1 expression,thus repairing spinal cord injury. METHODS:Exosomes were extracted from the cultured supernatant by the hyperspeed centrifugation method.The morphology of exosomes was observed by transmission electron microscope.The expression levels of tsg101 and CD63 were detected by western blot assay.Eighty SD rats were randomly divided into sham operation group,model group,exosome group,and endothelin-1 group(n=20).The modified Allen's method was used to create the rat model of spinal cord injury.In the endothelin-1 group,10 μL(1 μg/mL)endothelin-1 was injected directly into the injured area with a microsyringe.Immediately,1 day,2 days after operation,sham operation group and model group were injected with 200 μL PBS solution through the tail vein;the exosome group and endothelin-1 group were injected with 200 μL exosome(200 μg/mL)solution through the tail vein,respectively.Hind limb motor function scores were performed on days 1,3,7,14 and 21 after spinal cord injury.The blood-spinal cord barrier permeability was observed by Evans blue staining on day 7 after injury.The expression levels of tight junction proteins β-Catenin,ZO-1,Occludin and endothelin-1 in the spinal cord were detected by western blot assay. RESULTS AND CONCLUSION:(1)Basso-Beattie-Bresnahan score in the exosome group was significantly higher than that in the model group at 3-21 days after injury(P<0.05).Hematoxylin-eosin staining showed that spinal cord injury was greatly reduced in the exosome group compared with the model group.Basso-Beattie-Bresnahan score in the endothelin-1 group was significantly decreased compared with the exosome group(P<0.05).Spinal cord injury was more severe in the endothelin-1 group than that in the exosome group.(2)The expression of endothelin-1 in the model group was significantly increased compared with the sham operation group(P<0.05),and the expression of endothelin-1 in the exosome group was significantly decreased compared with the model group(P<0.05).(3)The blood-spinal cord barrier Evans blue exudate in the exosome group was significantly decreased compared with the model group(P<0.05).The expression levels of the tight junction proteins β-Catenin,Occludin and ZO-1 in the exosome group were increased(P<0.05);the Evans blue exudate in the endothelin-1 group was significantly increased compared with the exosome group(P<0.05).The expression level of tight junction protein was significantly decreased compared with the exosome group(P<0.05).(4)The results show that human umbilical cord mesenchymal cell-derived exosomes protect the permeability of the blood-spinal cord barrier by down-regulating the expression of endothelin-1 and play a role in the repair of spinal cord injury.
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BACKGROUND:To investigate the research focus and follow-up research trend of exosomes in the diagnosis and treatment of chronic kidney disease,in order to provide a corresponding reference basis for the future research of exosomes in the diagnosis and treatment of chronic kidney disease,and promote the development of this field. OBJECTIVE:To conduct a bibliometric analysis of relevant studies in each database painstakingly until now for public publication on exosome diagnosis and treatment of chronic kidney disease,to explore the current state and trend of the field in this discipline,and to predict future research directions. METHODS:A computerized search was performed on WanFang,CNKI,CBM,VIP,Web of Science,Cochrane Library,PubMed,and Embase databases from inception to December 2022 for published literature related to the diagnosis and treatment of chronic kidney disease by exosomes.The literature transcripts were screened by NoteExpress for co-occurrence,clustering and mutational analysis among authors,institutions,and keywords through CiteSpace 6.1R4 and VOSviewer software,and the visual knowledge map was plotted. RESULTS AND CONCLUSION:(1)A total of 804 articles,including 133 in Chinese and 671 in English,were included,and the volume of publications climbed year by year with a rapid trend.We included 3 649 literature authors,including 326 Chinese authors and 3 323 English authors,and the field has formed a core team centered on scholars such as Liu Bicheng,Wang Bin,Lyu LinLi,Wang Xiaonan and Wang Haidong,and has formed a stable multicenter collaboration platform among institutions.Research focuses on the three functions of exosomes:carrier,diagnosis and therapy.(2)As a form of extracellular vesicles,exosomes have important mechanisms for carrying,transferring molecular mediators and signal transduction,and have an important role in the physiopathological development of chronic kidney disease,which can provide important health surveillance data for epidemiological studies and clinical decision-making.In recent years,the development of relevant studies on exosome-based diagnosis of chronic kidney disease has expanded dramatically,forming a development layout of collaborative cooperation among multiple institutions worldwide,led by our scientific research institutions.However,at present,the study of the specific function and mechanism of action of exosomes and contents in the disease process has not been fully validated.Their significance for the early diagnosis and prognosis evaluation of chronic kidney disease is not very clear.The intrinsic mechanism of action-related research is still relatively poor.Isolation and purification techniques still need to be improved,and high-quality evidence-based clinical trials with multicenter and large samples have not yet appeared,which still need to be verified by further studies.
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BACKGROUND:Mesenchymal stem cells are multipotent stromal cells isolated from bone marrow,fat,umbilical cord and other tissues.It can differentiate into different cell types and secrete a variety of proteins with therapeutic potential,which has a good application prospect in the repair of muscle tissue. OBJECTIVE:To review the research progress of mesenchymal stem cells in promoting muscle tissue repair and provide a theoretical basis for further clinical application. METHODS:Relevant articles published from inception to 2022 were retrieved from CNKI,VIP,WanFang,PubMed,Embase and Web of Science databases.The keywords were"mesenchymal stem cells,muscle tissue,muscle injury,muscle atrophy,exosomes,scaffolds"in Chinese and English.The literature about mesenchymal stem cell migration promoting muscle fiber proliferation and repair was screened.Finally,98 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The related mechanisms of mesenchymal stem cell migration promoting muscle fiber proliferation and repair are complex,mostly by anti-inflammatory,inhibiting interstitial fibrosis,inhibiting the fat formation and other ways to promote muscle fiber proliferation and repair.(2)The related biological scaffolds and cell co-culture based on mesenchymal stem cells can significantly compensate for the low survival rate of mesenchymal stem cells after colonization.(3)At present,mesenchymal stem cell therapy still has apparent limitations.In the future,mesenchymal stem cells combined with other therapies should become the primary development trend.
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BACKGROUND:Extracellular vesicles can regulate insulin resistance and control inflammatory response by participating in intercellular communication,while repairing skeletal muscles and promoting skeletal muscle regeneration,which is expected to be a novel treatment modality for sarcopenic obesity. OBJECTIVE:To review the biogenesis of extracellular vesicles,their biological functions,their relationship with sarcopenic obesity,and recent advances in the pathogenesis,diagnosis,and treatment of sarcopenic obesity. METHODS:The first author performed a computer search of PubMed,Embase,CNKI and other databases for relevant studies involving extracellular vesicle in sarcopenic obesity.The search keywords were"extracellular vesicle,exosome,sarcopenic obesity,obese sarcopenia,skeletal muscle regeneration,skeletal muscle mass regulation"in English and Chinese,respectively.The search period was from June 2022 to November 2022.After screening,87 articles were included for further review. RESULTS AND CONCLUSION:Extracellular vesicles are important vectors of bidirectional cell communication and participate in the regulation of normal physiological and pathological processes through autocrine,paracrine and endocrine ways.Sarcopenic obesity is a complex multi-factor disease.Extracellular vesicles are involved in the occurrence and development of sarcopenic obesity mainly by regulating the inflammatory response of skeletal muscle and the homeostasis of muscle cells.Cytokines secreted by adipose tissue and skeletal muscle are released into the extracellular circulation through extracellular vesicle encapsulation and interact with each other to promote skeletal muscle insulin resistance and lipogenesis,which is the main pathophysiology of skeletal muscle atrophy in sarcopenic obesity.Extracellular vesicles not only promote the development of sarcopenic obesity by providing specific pathogenic markers,but also are a valuable diagnostic indicator of sarcopenic obesity.Release of extracellular vesicles from skeletal muscle during exercise enhances metabolic response and promotes skeletal muscle regeneration.Extracellular vesicles can not only be used as therapeutic targets for sarcopenic obesity but also be used to treat sarcopenic obesity by loading drugs to effectively improve drug bioavailability.
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BACKGROUND:A large number of studies have confirmed that exosomes can promote osteogenesis and vascularization.However,simple exosome therapy has problems such as poor targeting,and the content of loaded molecules cannot reach the therapeutic concentration. OBJECTIVE:To load exosomes into injectable gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel,and observe the effect of the hydrogel on peri-implant bone defect in vivo and in vitro. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells and wrapped in injectable gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel.(1)In vitro experiment:The hydrogel loaded with exosomes and the hydrogel without exosomes were cocultured with endothelial progenitor cells,and exosomes uptake experiment,tubule formation experiment,cell proliferation,migration ability,and angiogenic gene detection were carried out.(2)In vivo experiment:Twelve male New Zealand white rabbits were used to prepare two standard implant cavities and corresponding bone defects in the long axis of one femur.A hydrogel loaded with exosomes was implanted in the bone defect after an implant was implanted in a cavity at the proximal end of the implant(experimental group),and an unloaded exosome hydrogel was implanted in the bone defect after an implant was implanted in a cavity at the distal end of the implant(control group).At 3,6 and 9 weeks after operation,bone defects with implants were removed and stained with hematoxylin-eosin staining and Masson staining.Simultaneously,osteogenic and angiogenic genes were detected at 9 weeks after operation. RESULTS AND CONCLUSION:(1)In vitro experiment:Exosomes could enter endothelial progenitor cells.The proliferation,migration,angiogenesis and gene(CD31,vascular endothelial growth factor and basic fibroblast growth factor)expression of endothelial progenitor cells in the hydrogel-loaded group were higher than those in the hydrogel-unloaded group(P<0.05).(2)In vivo experiment:Hematoxylin-eosin staining and Masson staining showed that at 3 weeks after operation,only a small amount of new bone was found in the two groups,and the material was partially degraded.At 6 weeks after operation,the amount of new bone in the two groups increased,and a large amount of new bone was found in the experimental group,with obvious calcium deposition.At 9 weeks after operation,compared with the control group,a large number of bone trabeculae thicker than mature were found in the experimental group,calcium salt deposition was more obvious,and a large number of osteoblasts were found around the bone trabeculae.The protein expressions of CD31,vascular endothelial growth factor,basic fibroblast growth factor,bone morphogenetic protein 2,type I collagen and osteocalcin in the experimental group were higher than those in the control group at 9 weeks after operation(P<0.05).(3)The exosome-loaded gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel could promote the proliferation,migration and angiogenic differentiation of endothelial progenitor cells and promote the repair and regeneration of bone defects around implants.
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BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.
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BACKGROUND:Myocardial infarction is one of the most serious cardiovascular diseases at present,and the existing clinical treatment options such as thrombolytic therapy,percutaneous coronary intervention and coronary artery bypass grafting cannot fully restore the myocardial damage caused by ischemia.Stem cell-derived exosomes for the treatment of myocardial infarction have been a hot research topic in recent years,but the low yield of natural-derived exosomes,the difficulty and time consuming nature of obtaining them,and the poor homing effect have limited their clinical application.In this context,the construction of artificial exosomes as an alternative to natural exosomes has become an effective strategy to solve the above problems. OBJECTIVE:To expound the research status of artificial exosomes in the treatment of myocardial infarction,and classify them into two design modes:semi-artificial and full-artificial,and discuss the research progress and problems of the two modes,finally,make the evaluation and prospect of its clinical application in the future. METHODS:PubMed and CNKI were searched for relevant articles with"artificial exosomes,myocardial infarction,engineering"in Chinese,and"artificial exosome,hybrid exosome,myocardial infarction,nanoparticle,drug delivery system"in English.The focus of the search was from January 2017 to December 2022,and some of the classic forward literature was included.A preliminary selection was conducted through reading titles and abstracts.Repetitive studies,low-quality journals and irrelevant articles were excluded.Finally,73 articles were included for review. RESULTS AND CONCLUSION:(1)By semi-artificially modifying exosomes,whether it is the modification of targeting peptides,hybridization of biofilms or the assistance of magnetic substances,traditional exosome therapies with insufficient targeting and low retention rate and easy to be cleared by the reticuloendothelial system have improved the efficiency of traditional exosome therapy for myocardial infarction.However,these strategies have problems such as unclear modification efficiency,medical ethics,and biotoxicity.(2)Fully artificial bionic exosomes have a higher degree of design freedom compared to exosome modification,which can solve the problems of high extraction and storage difficulties of exosomes of natural origin and limitations of large-scale production;however,this artificial exosome strategy still lacks reliable preclinical data support and biosafety testing,and has not yet formed a standardized process required for large-scale production;therefore,before applying to the clinic,the artificial exosome solution as an alternative to natural exosomes still needs continuous in-depth research by researchers.
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OBJECTIVE:To evaluate the efficacy of exosomes derived from mesenchymal stem cells on animal models of acute liver failure. METHODS:PubMed,Web of Science,Embase,The Cochrane Library,CBM,CNKI,WanFang,and VIP databases were retrieved from inception to January 16,2023.A series of animal experiments on the treatment of acute liver failure animal models by exosomes derived from mesenchymal stem cells were collected.Two evaluators screened the literature and extracted the data independently.The bias risk was evaluated by the SYRCLE tool.The extracted data were analyzed by Revmen 5.4.1 software and Stata 17.0 software. RESULTS:A total of 241 articles were retrieved and 9 animal experiments were included,with 219 animals:110 animals in the model group and 109 animals in the exosome group.The results showed that the survival rate of animals in the exosome group improved significantly[RR=9.34,95%CI(3.91,22.29),P<0.001],the levels of serum alanine transaminase[SMD=-5.31,95%CI(-7.43,-3.19),P<0.001]and aspartate aminotransferase[SMD=-4.47,95%CI(-5.85,-3.10),P<0.001]were reduced obviously.The expressions of interleukin-1β[SMD=-11.54,95%CI(-18.12,-4.95),P=0.000 6],interleukin-6[SMD=-5.75,95%CI(-8.08,-3.41),P<0.001]and tumor necrosis factor-α[SMD=-4.46,95%CI(-6.83,-2.09),P=0.000 2],were suppressed obviously. CONCLUSION:Exosomes derived from mesenchymal stem cells effectively inhibit the inflammatory response,ameliorate liver function of animals with acute liver failure,and improve their survival rate.The results of subgroup analysis showed that the shorter survival time of animals(≤24 hours),the lower dose of transplanted exosomes(<1 mg/kg)and the source of exosomes(adipose-derived mesenchymal stem cells)may affect the efficacy of the exosomes derived from mesenchymal stem cells in the animal model of acute liver failure.This conclusion and its clinical transformation still need to be confirmed by randomized controlled studies with large sample sizes and high quality.
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BACKGROUND:Skin damage caused by radiation therapy and nuclear accidents is still a serious medical problem.It is difficult to achieve effective treatment results with single prevention and treatment methods.It is an important research direction to find new comprehensive treatment methods. OBJECTIVE:To observe the protective effect and the underlying mechanism of 1,2-propanediol combined with hepatocyte growth factor-modified exosomes derived from dental pulp stem cells on human epidermal radiation damage cell models. METHODS:(1)After infection of human dental pulp stem cells using recombinant adenovirus of human hepatocyte growth factor gene,exosomes,i.e.,Ad.HGF DPSC-Exo,were isolated with ultracentrifugation.(2)HaCat cells were irradiated with X-ray.The cells were treated with 1,2-propanediol before irradiation and Ad.HGF DPSC-Exo after irradiation.Cell proliferative activity was determined by CCK-8 assay.Cell apoptosis was detected by flow cytometry.Cell migration was detected by cell scratch assay.The expression levels of P21 and P53 were detected by PCR. RESULTS AND CONCLUSION:1,2-Propanediol,Ad.HGF.DPSC-Exo,Ad.HGF.DPSC-Exo + 1,2-propanediol could significantly improve the growth inhibition of HaCaT cells,reduce cell apoptosis,elevate cell proliferation and migration,and exhibit a good radiation protection effect.Moreover,the combined effect of Ad.HGF.DPSC-Exo + 1,2-propanediol was better.Furthermore,Ad.HGF.DPSC-Exo + 1,2-propanediol alleviated the cellular G2/M phase block and decreased the expression of cell cycle genes P53 and P21.In conclusion,1,2-propanediol pretreatment combined with Ad.HGF.DPSC-Exo had significant protective effects on radiation-induced HaCaT cell injury and it provided novel ideas and potential methods for the prevention and treatment of radiation-induced skin damage.
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BACKGROUND:Existing studies have confirmed that exosomes can effectively promote pulp regeneration.However,the biological functions and properties of exosomes from preconditioned sources can be significantly changed,which have different effects on cell proliferation,migration and odontogenic differentiation. OBJECTIVE:To discuss the application status of exosomes and their preconditioning methods in the field of pulp regeneration,and summarize the preconditioning methods that affect the function of exosomes,and explore the effect of exosomes and their preconditioning on pulp regeneration. METHODS:The relevant articles were searched in WanFang,CNKI,PubMed,and Web of Science databases from 2006 to 2022.The Chinese and English search terms were"exosomes,pulp regeneration;preconditioning method".A total of 78 articles were included for analysis. RESULTS AND CONCLUSION:(1)Exosomes have the advantages of good biocompatibility,low immunogenicity and no cytotoxicity,and can induce the regeneration of pulp tissue by promoting stem cell tooth formation,neurogenesis and vascularization.(2)Exosomes derived from preconditioning can enhance the ability of tissue repair and regeneration and have a significant impact on the quality of regenerated dental pulp.(3)Currently,the preconditioning methods used in the field of dental pulp regeneration include inflammatory stimulation,hypoxia induction,conditioned medium and three-dimensional culture,and secreted exosomes can effectively improve the quality of regenerated dental pulp.Nevertheless,the specific effect and mechanism of different preconditioning methods on pulp regeneration need to be explored.
RESUMEN
BACKGROUND:Cell derivative is cell-derived bioactive components,including decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium,has the effects on immune regulation,promoting angiogenesis,bone regeneration,ligament remodeling,and is capable of promoting stem cell chemotherapy,migration,proliferation,and adhesion.Its excellent characteristics make it a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering. OBJECTIVE:To review the characteristics of cell derivatives(decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium)and its effect and the latest progress in the field of regenerative restoration of periodontal complex tissue structures. METHODS:We searched the articles on CNKI and PubMed databases with the search terms"regeneration,periodontal tissue,tissue engineering,decellularized matrix,exosome,apoptotic extracellular vesicle,condition medium"in Chinese and English,respectively.Finally,76 articles were included for analysis and discussion. RESULTS AND CONCLUSION:(1)Among those four cell derivatives,the decellularized extracellular matrix has the best mechanical properties and fibrous structure,serving as a biomimetic scaffold to provide physiochemical signals and participate in mechanical signaling in periodontal tissue engineering,providing supporting effect suitable for periodontal regeneration.Recently,the development of soluble decellularized extracellular matrix bioinks has enabled the fabrication of regenerative scaffolds for personalized periodontal defects.(2)Exosomes are the simplest cell derivatives that have immunomodulatory capacity,promoting cell migration and differentiation.As a carrier,they can be used to carry target molecules to regulate periodontal regeneration,promote ligament remodeling and bone regeneration,and are suitable for periodontal tissue engineering.(3)Apoptotic vesicles generated from apoptotic cells have a strong immunomodulatory effect and can recruit stem cells and macrophages,which determine the fate of stem cells through signal transduction and can enhance immunomodulation to promote periodontal regeneration.Engineered extracellular vesicle is considered to have the potential to initiate targeted internal immunomodulation.(4)The extraction of conditioned medium is simple and completely noninvasive,which provides essential nutrients and growth factors for tissue regeneration.These components are crucial for successful periodontal regeneration.Therefore,the conditioned medium is especially suitable for studying the interactions between cells in vitro and has an important role in high-throughput detection in the future.