Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of life.Despite years of research there have been minimal therapeutic advances.Endothelial progenitor cells(EPCs),stem cel...Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of life.Despite years of research there have been minimal therapeutic advances.Endothelial progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic target.After a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'outcome.This study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic stroke.The study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled study.Blood samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 and90.EPCs will be counted with flow cytometry.The plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be determined.Outgrowth endothelial cells will be cultured to be used in tube formation,migration and proliferation functional assays.Primary outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin Scale.Secondary outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy volunteers.Recruitment started in February 2017,167 participants have been recruited.Recruitment will end in November 2019.West Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,2016.Protocol version:2.0.The Bayraktutan Dunhill Medical Trust EPC Study was registered in ClinicalTrials.gov(NCT02980354)on November 15,2016.This study will determine whether the number of EPCs can be used as a prognostic or diagnostic marker for ischemic strokes and is a step towards discovering if transplantation of EPCs may aid patient recovery.展开更多
Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as t...Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window(4.5 hours of stroke onset) and increased risk of hemorrhage beyond this point, each year globally less than 1% of stroke patients receive this therapy which necessitate the discovery of safe and efficacious therapeutics that can be used beyond the acute phase of stroke. Accumulating evidence indicates that endothelial progenitor cells(EPCs), equipped with an inherent capacity to migrate, proliferate and differentiate, may be one such therapeutics. However, the limited availability of EPCs in peripheral blood and early senescence of few isolated cells in culture conditions adversely affect their application as effective therapeutics. Given that much of the EPC-mediated reparative effects on neurovasculature is realized by a wide range of biologically active substances released by these cells, it is possible that EPC-secretome may serve as an important therapeutic after an ischemic stroke. In light of this assumption, this review paper firstly discusses the main constituents of EPC-secretome that may exert the beneficial effects of EPCs on neurovasculature, and then reviews the currently scant literature that focuses on its therapeutic capacity.展开更多
Intracerebral hemorrhage(ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to i...Intracerebral hemorrhage(ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells(EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.展开更多
Two isolation methods for sorting of endothelial progenitor cells(EPCs):from peripheral blood mononuclear cells(PBMCs)and CD133+ enriched cells were compared,by defining the cell morphology,phenotype,reproductive acti...Two isolation methods for sorting of endothelial progenitor cells(EPCs):from peripheral blood mononuclear cells(PBMCs)and CD133+ enriched cells were compared,by defining the cell morphology,phenotype,reproductive activities and function in vitro,to provide a reference for clinical application of EPCs.PBMCs from healthy subjects were used either directly for cell culture or for CD133+ sorting.The two groups of cells were cultured in complete medium 199(M199)for 7 to 14 days and the phenotypes of EPCs were analyzed by FACS.The proliferation of differentiated EPCs was studied by MTT assay,and the VEGF concentration was measured using an ELISA kit.ECM gel experiment and migration assay were performed in vivo.The results showed that PBMCs produced more colony-forming units(CFU)than CD133+ enriched cells from the same volume of blood(P<0.01).From day 7 to 14,the two groups showed decreased expression of hematopoietic stem cell markers and increased level of endothelial markers,but CD144+ cells in CD133+ group were less than in PBMCs group(P<0.01).PBMCs group secreted more VEGF than CD133+ group on the day 7(P<0.01).As compared with CD133+ group,PBMCs group had more potent potential of proliferation and vascularization in vitro.It was concluded that CD133+ sorted cells showed a lower capacity of differentiation,secretion,proliferation and vascularization in vitro,suggesting that CD133-negative cells may be a preferential way to get EPCs for clinical therapy.展开更多
Objective:To explore the effect of Sirt1 on the function of endothelial progenitor cells(EPCs)in rats with chronic obstructive pulmonary disease(COPD).Methods:A rat COPD model was established via smoking and endotoxin...Objective:To explore the effect of Sirt1 on the function of endothelial progenitor cells(EPCs)in rats with chronic obstructive pulmonary disease(COPD).Methods:A rat COPD model was established via smoking and endotoxin administration for three months.The peripheral circulating EPCs were isolated by gradient centrifugation,and their functions,cell cycle distribution,apoptosis,and Sirt1 expression were examined.The function changes of EPCs in the presence or absence of Sirt1 agonist and inhibitor were estimated;meanwhile,the expressions of Sirt1,FOXO3a,NF-κB,and p53 were also evaluated.Results:The proliferation,adhesion,and migration of EPCs decreased while the apoptosis rate was increased in the COPD rats.The expression of Sirt1 protein in EPCs of the COPD group was significantly lower than that in the control group(P<0.01).The overexpression of the Sirt1 gene using a gene transfection technique or Sirt1 agonists(SRT1720)improved the proliferation,migration,and adhesion,and decreased the apoptosis of EPC.However,Sirt1 inhibitor(EX527)decreased EPC functions in the COPD group.The effect of Sirt1 expression on EPC function may be related to reduction of FOXO3a and increase of NF-κB and p53 activity.Conclusions:Increased expression of Sirt1 can improve the proliferation and migration of EPCs and reduce their apoptosis in COPD rats.This change may be related to FOXO3a,NF-κB,and p53 signaling pathways.展开更多
Vascular injury is a frequent pathology in coronary artery disease.To repair the vasculature,scientists have found that endothelial progenitor cells(EPCs)have excellent properties associated with angiogenesis.Over tim...Vascular injury is a frequent pathology in coronary artery disease.To repair the vasculature,scientists have found that endothelial progenitor cells(EPCs)have excellent properties associated with angiogenesis.Over time,research on EPCs has made encouraging progress regardless of pathology or clinical technology.This review focuses on the origins and cell markers of EPCs,and the connection between EPCs and coronary artery disease.In addition,we summarized various studies of EPC-capturing stents and EPC infusion therapy,and aim to learn from past technology to predict the future.展开更多
BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endot...BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium.They also have low levels of endothelial progenitor cells(EPCs).EPCs are bone marrow derived cells involved in endothelium regeneration,homeostasis,and neovascularization.Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities.However,the effects of exercise on EPCs in different stages of CHF remain under investigation.AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing(CPET)on EPCs in CHF patients of different severity.METHODS Forty-nine consecutive patients(41 males)with stable CHF[mean age(years):56±10,ejection fraction(EF,%):32±8,peak oxygen uptake(VO2,mL/kg/min):18.1±4.4]underwent a CPET on a cycle ergometer.Venous blood was sampled before and after CPET.Five circulating endothelial populations were quantified by flow cytometry:Three subgroups of EPCs[CD34+/CD45-/CD133+,CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2(VEGFR2)]and two subgroups of circulating endothelial cells(CD34+/CD45-/CD133-and CD34+/CD45-/CD133-/VEGFR2).Patients were divided in two groups of severity according to the median value of peak VO2(18.0 mL/kg/min),predicted peak VO2(65.5%),ventilation/carbon dioxide output slope(32.5)and EF(reduced and mid-ranged EF).EPCs values are expressed as median(25th-75th percentiles)in cells/106 enucleated cells.RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:60(25-76)vs post CPET:90(70-103)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:1(1-4)vs post CPET:5(3-8)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133-[pre CPET:186(141-361)vs post CPET:488(247-658)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:2(1-2)vs post CPET:3(2-5)cells/106 enucleated cells,P<0.001],while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:42(19-73)vs post CPET:90(39-118)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:2(1-3)vs post CPET:6(3-9)cells/106 enucleated cells,P<0.001],CD34+/CD133+/VEGFR2[pre CPET:10(7-18)vs post CPET:14(10-19)cells/106 enucleated cells,P<0.01],CD34+/CD45-/CD133-[pre CPET:218(158-247)vs post CPET:311(254-569)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:1(1-2)vs post CPET:4(2-6)cells/106 enucleated cells,P<0.001].A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak,ventilation/carbon dioxide output slope and EF as well(P<0.05).However,there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison(P>0.05).CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients,but this increase was not associated with syndrome severity.Further investigation,however,is needed.展开更多
Ischaemic stroke is a debilitating disease with immense personal,societal and economic impact.Thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease.As ea...Ischaemic stroke is a debilitating disease with immense personal,societal and economic impact.Thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease.As each year less than 1%of eligible patients receive this therapy worldwide,efficacious new therapeutics are desperately needed.Emerging evidence suggest endothelial progenitor cells(EPCs),capable of repairing damaged vasculature,as one such therapeutics.However,questions regarding their optimal dose,delivery route and in vivo survivability remain largely unanswered.Outgrowth endothelial cells,generated in large numbers by ex vivo expansion of EPCs,enable effective assessment of these issues and may eventually serve as off-the-shelf therapeutics.Correlations between circulating EPC levels and stroke outcome imply that EPCs may also serve as clinical biomarkers for stroke.This viewpoint briefly evaluates the current evidence,pinpoints the gaps in the literature and proposes new directions for research.展开更多
Objective:To investigate the intervention effect of Buyang Huanwu Decoction on endothelial progenitor cell function(EPCs),and to explore the therapeutic mechanism of Buyang Huanwu Decoction.Methods:This research take ...Objective:To investigate the intervention effect of Buyang Huanwu Decoction on endothelial progenitor cell function(EPCs),and to explore the therapeutic mechanism of Buyang Huanwu Decoction.Methods:This research take 54 rats were divided into blank group,the control group,model group,Chinese medicine,western medicine group and combine traditional Chinese and western medicine group,tonifying Yang also five decoction and atorvastatin calcium for acute myocardial infarction(AMI)rats group intervention,by using the method of density gradient centrifugation separation training each rat endothelial progenitor cells,using tetramethyl azo salt trace enzyme reaction colorimetry,used in the determination of adhesion ability and improved Boyden chamber,the method of analysis and comparison between groups of endothelial progenitor cells proliferation,adhesion and migration.Results:In 7 days,14 days and 4 weeks,acute myocardial infarction model of rat peripheral blood EPCs count,proliferation,migration and adhesion ability were compared with control group were significantly decline,tonifying Yang also five decoction group,western medicine control group and combine traditional Chinese and western medicine group of peripheral blood EPCs count,proliferation,migration and adhesion ability compared with model group were significantly increased(P<0.05),and combine traditional Chinese and western medicine group is the traditional Chinese medicine and western medicine group on the improvement of the function of EPCs effect more significantly(P<0.05).Conclusion:Statins combined with Buyang Huanwu Decoction can better improve the endothelial function of AMI rats than traditional Chinese medicine or western medicine.Further clinical studies on statins may better improve the endothelial function of AMI patients,and provide a new research entry point for improving the long-term prognosis of AMI patients.展开更多
Previous studies suggest that reduction and dysfunction of circulating endothelial progenitor cells(EPCs),and dysregulation in stromal cell derived factor-1/CXC-chemokine receptor 4(SDF-1/ CXCR4) axis in diabetes coul...Previous studies suggest that reduction and dysfunction of circulating endothelial progenitor cells(EPCs),and dysregulation in stromal cell derived factor-1/CXC-chemokine receptor 4(SDF-1/ CXCR4) axis in diabetes could be therapeutic targets for diabetic ischemic stroke.This study investigated the efficacy of CXCR4-priming EPCs on cerebral repair following ischemic stroke in db/db diabetic mice.Bone marrow derived EPCs from db/+ control mice were transfected with adenovirus(1×10~7 IU) carrying CXCR4(Ad-CXCR4-EPCs)or null(Ad- null-EPCs).The db/db mice were divided into three groups for EPCs injection(2×10~5 cells/100μl): Ad-CXCR4-EPCs,Ad-null-EPCs or saline(vehicle), via tail vein 2 hrs after middle cerebral artery occlusion (MCAO) surgery.Cerebral blood flow(CBF) was measured with laser Doppler flowmeter.Mice were sacrificed at 2 or 7 days thereafter.Level of circulating EPCs was measured by flow cytometry. Ischemic damage,cerebral microvascular density (MVD),angiogenesis and neurogenesis were determined by histological staining with Fluoro-J,CD31, CD31 +BrdU,NeuN +BrdU,GFAP+BrdU,respectively. Results(table) showed:1) Levels of CXCR4 expression were reduced in the brain and EPCs of db/db mice as measured by real-time RT-PCR and western blot analyses(data not shown);2) The level of circulating EPCs was more in the mice treated with Ad-CXCR4-EPCs;3)EPC transfusion improved CBF,increased MVD,angiogenesis and neurogenesis in peri-infarct area,and decreased ischemic damage.The efficacies were better in Ad-CXCR4 -EPCs group.Data suggest that transfusion of Ad-CXCR4-EPCs could be a therapeutic avenue for ischemia stroke in diabetes.展开更多
Objective:To investigate the effect of Benner Pury on Endothelial progenitor cells(EPCs)proliferation,migration,adhesion,apoptosis and oxidative stress in vitro from patients with hypertension and its time dependence....Objective:To investigate the effect of Benner Pury on Endothelial progenitor cells(EPCs)proliferation,migration,adhesion,apoptosis and oxidative stress in vitro from patients with hypertension and its time dependence.Methods:The patients who were diagnosed as hypertension grade 1 according to the standard“Guidelines for Prevention and Treatment of Hypertension”were enrolled.Mononuclear cells were isolated by density gradient centrifugation and stained with fluorescence chemical acetylated low density lipoprotein marked with DiI(acLDL-DiI)and fluorescein isothiocyanate(FITC)-lectin.Double staining positive cells were considered as the differentiation of EPCs.The control group included healthy subjects matched with study group in age,gender.EPCs cultivated for 5 days were used for study.Cells harvested at different set times under the stimulation of Benner Pury,and the EPCs proliferation,migration,adhesion ability,apoptosis and oxidative stress indicators were detected respectively.Results:(1)Compared with the control group,peripheral blood EPCs proliferation,migration and adhesion ability were ob-viously decreased in the hypertension group(p<.01),EPCs apoptosis rate and oxidative stress response were significantly increased(p<.01).(2)Benner Pury significantly increased the EPCs proliferation,migration,adhesion ability and improved apoptosis and oxidative stress reaction in a time-dependent manner.Conclusions:Benner Pury can improve the EPCs proliferation,migration,adhesion,apoptosis and oxidative stress in patients with hypertension in a time-dependent manner.展开更多
Diabetic ischemic wound treatment remains a critical clinical challenge.Neovascularization plays a significant role in wound healing during all stages of the tissue repair process.Strategies that enhance angiogenesis ...Diabetic ischemic wound treatment remains a critical clinical challenge.Neovascularization plays a significant role in wound healing during all stages of the tissue repair process.Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds,particularly diabetic wounds in highly ischemic conditions.We previously identified a cyclic peptide LXW7 that specifically binds to integrinαvβ3 on endothelial progenitor cells(EPCs)and endothelial cells(ECs),activates vascular endothelial growth factor(VEGF)receptors,and promotes EC growth and maturation.In this study,we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides(SILY)to a dermatan sulfate(DS)glycosaminoglycan backbone,named LXW7-DS-SILY,and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix(ECM)scaffolds.We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment.When applied in an established Zucker Diabetic Fatty(ZDF)rat ischemic skin flap model,LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing,enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment.Altogether,this study provides a promising novel treatment to accelerate diabetic ischemic wound healing,thereby reducing limb amputation and mortality of diabetic patients.展开更多
Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both...Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both cell populations have been already studied and used for their regenerative potentials,recently their special immunoregulatory features have brought much more attention.Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response,particularly T cell proliferation,activation,and cytokine production.This makes them suitable choices for allogeneic stem cell transplantation.Nevertheless,these two cells do not have equal immunoregulatory activities.Many elements including their extraction sources,age/passage,expression of different markers,secretion of bioactive mediators,and some others could change the efficiency of their immunosuppressive function.However,to our knowledge,no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells.This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression,deactivation,cytokine production,and regulatory T cells induction capacities.Moreover,it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.展开更多
Background:Pulmonary hypertension(PH)is a progressive disease characterized by lung endothelial cell dysfunction and Vascular remodeling.Endothelial progenitor cells(EPCs)have been proved to be a potential therapeutic...Background:Pulmonary hypertension(PH)is a progressive disease characterized by lung endothelial cell dysfunction and Vascular remodeling.Endothelial progenitor cells(EPCs)have been proved to be a potential therapeutic strategy to treat PH.Autophagy has been found to be protective to hypoxia-induced PH.In this study,we applied high shear stress(HSS)-induced PH,and examined whether EPCs confer resistance against HSS-induced PH through autophagy.Methods:Pulmonary microvascular endothelial cells(PMVECs)were cultured under HSS with pro-inflammatory factors in an artificial capillary system to mimic the PH condition.Levels of p62,a selective autophagy substrate,were quantified by western blotting.Cell viability was determined by trypan blue exclusion test.Results:The p62 level in PMVECs was increased at 4 hours after HSS,peaked at 12 hours and declined at 24 hours.The cell viability gradually decreased.Compared with PMVECs cultured by empty medium,in cells cultured by EPC-conditioned medium(EPC-CM),the cell viability was significantly higher;however,p62 levels were also significantly higher,suggesting inhibition of autophagy by EPC-CM.Adding choloquine to suppress autophagy decreased the cell viability of PMVECs under PH.Conclusions:EPC-CM could suppress the autophagic activity of PMVECs in HSS-induced PH.However,suppression of autophagy leads to ceil death.EPCs could fight against PH through cellular or molecular pathways independent of autophagy.But it is not proved if induction of autophagy could be a potential strategy to treat HSS-induced PH as hypoxia-induced PH.展开更多
Key to most implanted cell free scaffolds for tissue regeneration is the ability to sequester and retain undifferentiated mesenchymal stem cells at the repair site.In this report,syndecan-4,a heparan sulfate containin...Key to most implanted cell free scaffolds for tissue regeneration is the ability to sequester and retain undifferentiated mesenchymal stem cells at the repair site.In this report,syndecan-4,a heparan sulfate containing proteoglycan,was investigated as a unique molecule for use in scaffold functionalization.An electrospun hybrid scaffold comprised of poly(glycerol)sebacate(PGS),silk fibroin and type I collagen(PFC)was used as a model scaffold to develop a procedure and test the hypothesis that functionalization would result in increased scaffold binding of endothelial progenitor cells(EPCs).For these studies both Syndecan-4 and stromal derived factor-1a(SDF-1a)were used in functionalization PFC.Syndecan-4 functionalized PFC bound 4.8 fold more SDF-1a compared to nonfunctionalized PFC.Binding was specific as determined by heparin displacement studies.After culture for 7 days,significantly,more EPCs were detected on PFC scaffolds having both syndecan-4 and SDF-1a compared to scaffolds of PFC with only syndecan-4,or PFC adsorbed with SDF-1a,or PFC alone.Taken together,this study demonstrates that EPCs can be bound to and significantly expanded on PFC material through syndecan-4 mediated growth factor binding.Syndecan-4 with a multiplicity of binding sites has the potential to functionalize and expand stem cells on a variety of scaffold materials for use in tissue regeneration.展开更多
We synthesized B-He/B-GREDVY and immobilized them on avidin-coated surfaces.To examine the immobilization of molecules in the material, the following experiments were performed:fluorescein isothiocyanate(FITC) fluores...We synthesized B-He/B-GREDVY and immobilized them on avidin-coated surfaces.To examine the immobilization of molecules in the material, the following experiments were performed:fluorescein isothiocyanate(FITC) fluorescence staining, water contact angle and atomic force microscopy(AFM) measurements. Besides, the biological evaluation experiments were also performed, such as platelets adhesion and activation, the culturing of smooth muscle cells(SMC) and endothelial cells(EC). These experimental results show that the modified surfaces could prevent the hyperproliferation of SMC, and promote the proliferation and migration of EC and EPC. Furthermore, the adding of VEGF improved the EC adhesion in a dynamic environment. Generally, it is expected that the modified surfaces could be used to accelerate the formation of the newly endothelial layer for the construction of platforms for coronary artery stent therapy.展开更多
Burn wounds result in varying degrees of soft tissue damage that are typically graded clinically.Recently a key participant in neovascularization,the endothelial progenitor cel,has been the subject of intense cardiova...Burn wounds result in varying degrees of soft tissue damage that are typically graded clinically.Recently a key participant in neovascularization,the endothelial progenitor cel,has been the subject of intense cardiovascular research to explore whether it can serve as a biomarker for vascular injury.In this review,we examine the identity of the endothelial progenitor cell as well as the evidence that support its role as a key responder after burn insult.While there is conflicting evidence with regards to the delta of endothelial progenitor cell mobilization and burn severity,it is clear that they play an important role in wound healing.Systematic and controlled studies are needed to clarify this relationship,and whether this population can serve as a biomarker for burn severity.展开更多
CD34+cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine.Naturally,these cells are mobilized from the bone marrow into peripheral circulati...CD34+cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine.Naturally,these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury.CD34+cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage.They have an important paracrine activity in secreting factors to stimulate vasculogenesis,reduce endothelial cells and cardiomyocytes apoptosis,remodel extracellular matrix and activate additional progenitor cells.Once they migrate to the target site,they enhance angiogenesis,neovascularization and tissue regeneration.Several trials have demonstrated the safety and efficacy of CD34+cell therapy in different settings,such as peripheral limb ischemia,stroke and cardiovascular disease.Herein,we review the potential utility of CD34+cell transplantation in acute myocardial infarction,refractory angina and ischemic heart failure.展开更多
The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injur...The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.展开更多
It is not clear what effects of CD34-and CD133-specific antibody-coated stents have on reendothelialization and in-stent restenosis(ISR)at the early phase of vascular injury.This study aims at determining the capabili...It is not clear what effects of CD34-and CD133-specific antibody-coated stents have on reendothelialization and in-stent restenosis(ISR)at the early phase of vascular injury.This study aims at determining the capabilities of different coatings on stents(e.g.gelatin,anti-CD133 and anti-CD34 antibodies)to promote adhesion and proliferation of endothelial progenitor cells(EPCs).The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flow-induced shear stress,so that allowing for the growth of the cells on the slides for 48 h.The in vivo experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents(BMS)and gelatin-coated stents.Compared with the anti-CD34 antibody-coated stents,the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR.In conclusion,this study demonstrated that anti-CD133 antibody as a stent coating for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR.展开更多
基金supported by a grant to Dr Ulvi Bayraktutan from The Dunhill Medical Trust(R459/0216)
文摘Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of life.Despite years of research there have been minimal therapeutic advances.Endothelial progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic target.After a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'outcome.This study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic stroke.The study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled study.Blood samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 and90.EPCs will be counted with flow cytometry.The plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be determined.Outgrowth endothelial cells will be cultured to be used in tube formation,migration and proliferation functional assays.Primary outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin Scale.Secondary outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy volunteers.Recruitment started in February 2017,167 participants have been recruited.Recruitment will end in November 2019.West Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,2016.Protocol version:2.0.The Bayraktutan Dunhill Medical Trust EPC Study was registered in ClinicalTrials.gov(NCT02980354)on November 15,2016.This study will determine whether the number of EPCs can be used as a prognostic or diagnostic marker for ischemic strokes and is a step towards discovering if transplantation of EPCs may aid patient recovery.
文摘Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window(4.5 hours of stroke onset) and increased risk of hemorrhage beyond this point, each year globally less than 1% of stroke patients receive this therapy which necessitate the discovery of safe and efficacious therapeutics that can be used beyond the acute phase of stroke. Accumulating evidence indicates that endothelial progenitor cells(EPCs), equipped with an inherent capacity to migrate, proliferate and differentiate, may be one such therapeutics. However, the limited availability of EPCs in peripheral blood and early senescence of few isolated cells in culture conditions adversely affect their application as effective therapeutics. Given that much of the EPC-mediated reparative effects on neurovasculature is realized by a wide range of biologically active substances released by these cells, it is possible that EPC-secretome may serve as an important therapeutic after an ischemic stroke. In light of this assumption, this review paper firstly discusses the main constituents of EPC-secretome that may exert the beneficial effects of EPCs on neurovasculature, and then reviews the currently scant literature that focuses on its therapeutic capacity.
基金supported by grants from the Spanish Ministry of Economy and Competitiveness(SAF2014-56336)the Instituto de Salud Carlos III(PI13/00292&PI14/01879)+5 种基金the Spanish Research Network on Cerebrovascular Diseases(RETICS INVICTUSRD12/0014)the Xunta de Galicia(Department of Education,GRC2014/027)the European Union program FEDERF.Campos(CP14/00154)TS(CP12/03121)are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III
文摘Intracerebral hemorrhage(ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells(EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.
文摘Two isolation methods for sorting of endothelial progenitor cells(EPCs):from peripheral blood mononuclear cells(PBMCs)and CD133+ enriched cells were compared,by defining the cell morphology,phenotype,reproductive activities and function in vitro,to provide a reference for clinical application of EPCs.PBMCs from healthy subjects were used either directly for cell culture or for CD133+ sorting.The two groups of cells were cultured in complete medium 199(M199)for 7 to 14 days and the phenotypes of EPCs were analyzed by FACS.The proliferation of differentiated EPCs was studied by MTT assay,and the VEGF concentration was measured using an ELISA kit.ECM gel experiment and migration assay were performed in vivo.The results showed that PBMCs produced more colony-forming units(CFU)than CD133+ enriched cells from the same volume of blood(P<0.01).From day 7 to 14,the two groups showed decreased expression of hematopoietic stem cell markers and increased level of endothelial markers,but CD144+ cells in CD133+ group were less than in PBMCs group(P<0.01).PBMCs group secreted more VEGF than CD133+ group on the day 7(P<0.01).As compared with CD133+ group,PBMCs group had more potent potential of proliferation and vascularization in vitro.It was concluded that CD133+ sorted cells showed a lower capacity of differentiation,secretion,proliferation and vascularization in vitro,suggesting that CD133-negative cells may be a preferential way to get EPCs for clinical therapy.
基金supported by NSCF(No.81260010,81460006 and 81660011)Hainan Natural Science Fund(No.20168264,817134)supported by Hainan Clinical Medical Center,China,we express our appreciation for their funding.
文摘Objective:To explore the effect of Sirt1 on the function of endothelial progenitor cells(EPCs)in rats with chronic obstructive pulmonary disease(COPD).Methods:A rat COPD model was established via smoking and endotoxin administration for three months.The peripheral circulating EPCs were isolated by gradient centrifugation,and their functions,cell cycle distribution,apoptosis,and Sirt1 expression were examined.The function changes of EPCs in the presence or absence of Sirt1 agonist and inhibitor were estimated;meanwhile,the expressions of Sirt1,FOXO3a,NF-κB,and p53 were also evaluated.Results:The proliferation,adhesion,and migration of EPCs decreased while the apoptosis rate was increased in the COPD rats.The expression of Sirt1 protein in EPCs of the COPD group was significantly lower than that in the control group(P<0.01).The overexpression of the Sirt1 gene using a gene transfection technique or Sirt1 agonists(SRT1720)improved the proliferation,migration,and adhesion,and decreased the apoptosis of EPC.However,Sirt1 inhibitor(EX527)decreased EPC functions in the COPD group.The effect of Sirt1 expression on EPC function may be related to reduction of FOXO3a and increase of NF-κB and p53 activity.Conclusions:Increased expression of Sirt1 can improve the proliferation and migration of EPCs and reduce their apoptosis in COPD rats.This change may be related to FOXO3a,NF-κB,and p53 signaling pathways.
基金Supported by the Guizhou Science and Technology Department,No.Qian-Ke-He[2018]1097the National Natural Science Foundation of China,No.81560056+2 种基金Program for Training Outstanding Young Scientific and Technological Talents of Guizhou Province,No.Qian Kehe Platform Talents[2019]5662Program for the Scientific Activities of Selected Returned Overseas Professionals in Guizhou Province,No.Grant Qian-Ren[2018]0003Scientific and Technological Platform and Talent Team Project of Guizhou Province,No.Qian Kehe Platform Talents[2017]5405.
文摘Vascular injury is a frequent pathology in coronary artery disease.To repair the vasculature,scientists have found that endothelial progenitor cells(EPCs)have excellent properties associated with angiogenesis.Over time,research on EPCs has made encouraging progress regardless of pathology or clinical technology.This review focuses on the origins and cell markers of EPCs,and the connection between EPCs and coronary artery disease.In addition,we summarized various studies of EPC-capturing stents and EPC infusion therapy,and aim to learn from past technology to predict the future.
基金Greece and the European Union(European Social Fund-ESF)through the Operational Programme“Human Resources Development,Education and Lifelong Learning”in the context of the project“Strengthening Human Resources Research Potential via Doctorate Research”(MIS-5000432),implemented by the State Scholarships Foundation(ΙΚΥ)the special account for research grants of the National and Kapodistrian University of Athens,Athens,Greece.
文摘BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium.They also have low levels of endothelial progenitor cells(EPCs).EPCs are bone marrow derived cells involved in endothelium regeneration,homeostasis,and neovascularization.Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities.However,the effects of exercise on EPCs in different stages of CHF remain under investigation.AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing(CPET)on EPCs in CHF patients of different severity.METHODS Forty-nine consecutive patients(41 males)with stable CHF[mean age(years):56±10,ejection fraction(EF,%):32±8,peak oxygen uptake(VO2,mL/kg/min):18.1±4.4]underwent a CPET on a cycle ergometer.Venous blood was sampled before and after CPET.Five circulating endothelial populations were quantified by flow cytometry:Three subgroups of EPCs[CD34+/CD45-/CD133+,CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2(VEGFR2)]and two subgroups of circulating endothelial cells(CD34+/CD45-/CD133-and CD34+/CD45-/CD133-/VEGFR2).Patients were divided in two groups of severity according to the median value of peak VO2(18.0 mL/kg/min),predicted peak VO2(65.5%),ventilation/carbon dioxide output slope(32.5)and EF(reduced and mid-ranged EF).EPCs values are expressed as median(25th-75th percentiles)in cells/106 enucleated cells.RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:60(25-76)vs post CPET:90(70-103)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:1(1-4)vs post CPET:5(3-8)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133-[pre CPET:186(141-361)vs post CPET:488(247-658)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:2(1-2)vs post CPET:3(2-5)cells/106 enucleated cells,P<0.001],while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:42(19-73)vs post CPET:90(39-118)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:2(1-3)vs post CPET:6(3-9)cells/106 enucleated cells,P<0.001],CD34+/CD133+/VEGFR2[pre CPET:10(7-18)vs post CPET:14(10-19)cells/106 enucleated cells,P<0.01],CD34+/CD45-/CD133-[pre CPET:218(158-247)vs post CPET:311(254-569)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:1(1-2)vs post CPET:4(2-6)cells/106 enucleated cells,P<0.001].A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak,ventilation/carbon dioxide output slope and EF as well(P<0.05).However,there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison(P>0.05).CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients,but this increase was not associated with syndrome severity.Further investigation,however,is needed.
基金This work was supported by a grant to Dr.Ulvi Bayraktutan from the Dunhill Medical Trust(R459/0216)The funder had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.The contents are solely the responsibility of the author and do not necessarily represent the official views of the DMT.
文摘Ischaemic stroke is a debilitating disease with immense personal,societal and economic impact.Thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease.As each year less than 1%of eligible patients receive this therapy worldwide,efficacious new therapeutics are desperately needed.Emerging evidence suggest endothelial progenitor cells(EPCs),capable of repairing damaged vasculature,as one such therapeutics.However,questions regarding their optimal dose,delivery route and in vivo survivability remain largely unanswered.Outgrowth endothelial cells,generated in large numbers by ex vivo expansion of EPCs,enable effective assessment of these issues and may eventually serve as off-the-shelf therapeutics.Correlations between circulating EPC levels and stroke outcome imply that EPCs may also serve as clinical biomarkers for stroke.This viewpoint briefly evaluates the current evidence,pinpoints the gaps in the literature and proposes new directions for research.
基金Regional fund project of the national natural science foundation of China(No.81660778)。
文摘Objective:To investigate the intervention effect of Buyang Huanwu Decoction on endothelial progenitor cell function(EPCs),and to explore the therapeutic mechanism of Buyang Huanwu Decoction.Methods:This research take 54 rats were divided into blank group,the control group,model group,Chinese medicine,western medicine group and combine traditional Chinese and western medicine group,tonifying Yang also five decoction and atorvastatin calcium for acute myocardial infarction(AMI)rats group intervention,by using the method of density gradient centrifugation separation training each rat endothelial progenitor cells,using tetramethyl azo salt trace enzyme reaction colorimetry,used in the determination of adhesion ability and improved Boyden chamber,the method of analysis and comparison between groups of endothelial progenitor cells proliferation,adhesion and migration.Results:In 7 days,14 days and 4 weeks,acute myocardial infarction model of rat peripheral blood EPCs count,proliferation,migration and adhesion ability were compared with control group were significantly decline,tonifying Yang also five decoction group,western medicine control group and combine traditional Chinese and western medicine group of peripheral blood EPCs count,proliferation,migration and adhesion ability compared with model group were significantly increased(P<0.05),and combine traditional Chinese and western medicine group is the traditional Chinese medicine and western medicine group on the improvement of the function of EPCs effect more significantly(P<0.05).Conclusion:Statins combined with Buyang Huanwu Decoction can better improve the endothelial function of AMI rats than traditional Chinese medicine or western medicine.Further clinical studies on statins may better improve the endothelial function of AMI patients,and provide a new research entry point for improving the long-term prognosis of AMI patients.
文摘Previous studies suggest that reduction and dysfunction of circulating endothelial progenitor cells(EPCs),and dysregulation in stromal cell derived factor-1/CXC-chemokine receptor 4(SDF-1/ CXCR4) axis in diabetes could be therapeutic targets for diabetic ischemic stroke.This study investigated the efficacy of CXCR4-priming EPCs on cerebral repair following ischemic stroke in db/db diabetic mice.Bone marrow derived EPCs from db/+ control mice were transfected with adenovirus(1×10~7 IU) carrying CXCR4(Ad-CXCR4-EPCs)or null(Ad- null-EPCs).The db/db mice were divided into three groups for EPCs injection(2×10~5 cells/100μl): Ad-CXCR4-EPCs,Ad-null-EPCs or saline(vehicle), via tail vein 2 hrs after middle cerebral artery occlusion (MCAO) surgery.Cerebral blood flow(CBF) was measured with laser Doppler flowmeter.Mice were sacrificed at 2 or 7 days thereafter.Level of circulating EPCs was measured by flow cytometry. Ischemic damage,cerebral microvascular density (MVD),angiogenesis and neurogenesis were determined by histological staining with Fluoro-J,CD31, CD31 +BrdU,NeuN +BrdU,GFAP+BrdU,respectively. Results(table) showed:1) Levels of CXCR4 expression were reduced in the brain and EPCs of db/db mice as measured by real-time RT-PCR and western blot analyses(data not shown);2) The level of circulating EPCs was more in the mice treated with Ad-CXCR4-EPCs;3)EPC transfusion improved CBF,increased MVD,angiogenesis and neurogenesis in peri-infarct area,and decreased ischemic damage.The efficacies were better in Ad-CXCR4 -EPCs group.Data suggest that transfusion of Ad-CXCR4-EPCs could be a therapeutic avenue for ischemia stroke in diabetes.
文摘Objective:To investigate the effect of Benner Pury on Endothelial progenitor cells(EPCs)proliferation,migration,adhesion,apoptosis and oxidative stress in vitro from patients with hypertension and its time dependence.Methods:The patients who were diagnosed as hypertension grade 1 according to the standard“Guidelines for Prevention and Treatment of Hypertension”were enrolled.Mononuclear cells were isolated by density gradient centrifugation and stained with fluorescence chemical acetylated low density lipoprotein marked with DiI(acLDL-DiI)and fluorescein isothiocyanate(FITC)-lectin.Double staining positive cells were considered as the differentiation of EPCs.The control group included healthy subjects matched with study group in age,gender.EPCs cultivated for 5 days were used for study.Cells harvested at different set times under the stimulation of Benner Pury,and the EPCs proliferation,migration,adhesion ability,apoptosis and oxidative stress indicators were detected respectively.Results:(1)Compared with the control group,peripheral blood EPCs proliferation,migration and adhesion ability were ob-viously decreased in the hypertension group(p<.01),EPCs apoptosis rate and oxidative stress response were significantly increased(p<.01).(2)Benner Pury significantly increased the EPCs proliferation,migration,adhesion ability and improved apoptosis and oxidative stress reaction in a time-dependent manner.Conclusions:Benner Pury can improve the EPCs proliferation,migration,adhesion,apoptosis and oxidative stress in patients with hypertension in a time-dependent manner.
基金partially supported by California Institute for Regenerative Medicine[grant number DISC1-10516-0]Shriners Hospitals for Children developmental research award[grant number 87200-NCA-19]supported by NCI P30CA093373 Cancer Center Support Grant.
文摘Diabetic ischemic wound treatment remains a critical clinical challenge.Neovascularization plays a significant role in wound healing during all stages of the tissue repair process.Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds,particularly diabetic wounds in highly ischemic conditions.We previously identified a cyclic peptide LXW7 that specifically binds to integrinαvβ3 on endothelial progenitor cells(EPCs)and endothelial cells(ECs),activates vascular endothelial growth factor(VEGF)receptors,and promotes EC growth and maturation.In this study,we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides(SILY)to a dermatan sulfate(DS)glycosaminoglycan backbone,named LXW7-DS-SILY,and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix(ECM)scaffolds.We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment.When applied in an established Zucker Diabetic Fatty(ZDF)rat ischemic skin flap model,LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing,enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment.Altogether,this study provides a promising novel treatment to accelerate diabetic ischemic wound healing,thereby reducing limb amputation and mortality of diabetic patients.
文摘Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both cell populations have been already studied and used for their regenerative potentials,recently their special immunoregulatory features have brought much more attention.Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response,particularly T cell proliferation,activation,and cytokine production.This makes them suitable choices for allogeneic stem cell transplantation.Nevertheless,these two cells do not have equal immunoregulatory activities.Many elements including their extraction sources,age/passage,expression of different markers,secretion of bioactive mediators,and some others could change the efficiency of their immunosuppressive function.However,to our knowledge,no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells.This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression,deactivation,cytokine production,and regulatory T cells induction capacities.Moreover,it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.
基金supported by grants from the Natural Science Foundation of Zhejiang Province(LY12H01005)Health Bureau of Zhejiang Province(2010KYA122)+6 种基金Natural Science Foundation of China(81202021)Ministry of Education Doctor Station Foundation(20120101110049)National Science and Technology Support Program(2012BAI04B05)National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(2013ZX09303003)National Key Technology R&D Program(2012BAI04B04)National Natural Science Foundation of China(81270722 and 8141480)Key Laboratory for Diagnosis and Therapy of Neonatal Diseases of Zhejiang Province
文摘Background:Pulmonary hypertension(PH)is a progressive disease characterized by lung endothelial cell dysfunction and Vascular remodeling.Endothelial progenitor cells(EPCs)have been proved to be a potential therapeutic strategy to treat PH.Autophagy has been found to be protective to hypoxia-induced PH.In this study,we applied high shear stress(HSS)-induced PH,and examined whether EPCs confer resistance against HSS-induced PH through autophagy.Methods:Pulmonary microvascular endothelial cells(PMVECs)were cultured under HSS with pro-inflammatory factors in an artificial capillary system to mimic the PH condition.Levels of p62,a selective autophagy substrate,were quantified by western blotting.Cell viability was determined by trypan blue exclusion test.Results:The p62 level in PMVECs was increased at 4 hours after HSS,peaked at 12 hours and declined at 24 hours.The cell viability gradually decreased.Compared with PMVECs cultured by empty medium,in cells cultured by EPC-conditioned medium(EPC-CM),the cell viability was significantly higher;however,p62 levels were also significantly higher,suggesting inhibition of autophagy by EPC-CM.Adding choloquine to suppress autophagy decreased the cell viability of PMVECs under PH.Conclusions:EPC-CM could suppress the autophagic activity of PMVECs in HSS-induced PH.However,suppression of autophagy leads to ceil death.EPCs could fight against PH through cellular or molecular pathways independent of autophagy.But it is not proved if induction of autophagy could be a potential strategy to treat HSS-induced PH as hypoxia-induced PH.
基金supported by the Harold S.Geneen Charitable Trust Awards Program for Coronary Heart Disease Research(W.D.W)the Wake Forest School of Medicine Department of Plastic and Reconstructive Surgery.
文摘Key to most implanted cell free scaffolds for tissue regeneration is the ability to sequester and retain undifferentiated mesenchymal stem cells at the repair site.In this report,syndecan-4,a heparan sulfate containing proteoglycan,was investigated as a unique molecule for use in scaffold functionalization.An electrospun hybrid scaffold comprised of poly(glycerol)sebacate(PGS),silk fibroin and type I collagen(PFC)was used as a model scaffold to develop a procedure and test the hypothesis that functionalization would result in increased scaffold binding of endothelial progenitor cells(EPCs).For these studies both Syndecan-4 and stromal derived factor-1a(SDF-1a)were used in functionalization PFC.Syndecan-4 functionalized PFC bound 4.8 fold more SDF-1a compared to nonfunctionalized PFC.Binding was specific as determined by heparin displacement studies.After culture for 7 days,significantly,more EPCs were detected on PFC scaffolds having both syndecan-4 and SDF-1a compared to scaffolds of PFC with only syndecan-4,or PFC adsorbed with SDF-1a,or PFC alone.Taken together,this study demonstrates that EPCs can be bound to and significantly expanded on PFC material through syndecan-4 mediated growth factor binding.Syndecan-4 with a multiplicity of binding sites has the potential to functionalize and expand stem cells on a variety of scaffold materials for use in tissue regeneration.
基金Funded by the National Natural Science Foundation of China(Nos.32271377 and 31870955)the National Key Research and Development of China (No.2020YFC1107300-03)。
文摘We synthesized B-He/B-GREDVY and immobilized them on avidin-coated surfaces.To examine the immobilization of molecules in the material, the following experiments were performed:fluorescein isothiocyanate(FITC) fluorescence staining, water contact angle and atomic force microscopy(AFM) measurements. Besides, the biological evaluation experiments were also performed, such as platelets adhesion and activation, the culturing of smooth muscle cells(SMC) and endothelial cells(EC). These experimental results show that the modified surfaces could prevent the hyperproliferation of SMC, and promote the proliferation and migration of EC and EPC. Furthermore, the adding of VEGF improved the EC adhesion in a dynamic environment. Generally, it is expected that the modified surfaces could be used to accelerate the formation of the newly endothelial layer for the construction of platforms for coronary artery stent therapy.
基金This work was supported in part by the California Institute for Regenerative Medicine training grant award TG2-012252 from the University of California,Irvine
文摘Burn wounds result in varying degrees of soft tissue damage that are typically graded clinically.Recently a key participant in neovascularization,the endothelial progenitor cel,has been the subject of intense cardiovascular research to explore whether it can serve as a biomarker for vascular injury.In this review,we examine the identity of the endothelial progenitor cell as well as the evidence that support its role as a key responder after burn insult.While there is conflicting evidence with regards to the delta of endothelial progenitor cell mobilization and burn severity,it is clear that they play an important role in wound healing.Systematic and controlled studies are needed to clarify this relationship,and whether this population can serve as a biomarker for burn severity.
文摘CD34+cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine.Naturally,these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury.CD34+cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage.They have an important paracrine activity in secreting factors to stimulate vasculogenesis,reduce endothelial cells and cardiomyocytes apoptosis,remodel extracellular matrix and activate additional progenitor cells.Once they migrate to the target site,they enhance angiogenesis,neovascularization and tissue regeneration.Several trials have demonstrated the safety and efficacy of CD34+cell therapy in different settings,such as peripheral limb ischemia,stroke and cardiovascular disease.Herein,we review the potential utility of CD34+cell transplantation in acute myocardial infarction,refractory angina and ischemic heart failure.
基金supported by the Natural Science Foundation of Guizhou Province in China,No.Qiankehe J(2013)2311
文摘The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.
基金This study was partially supported by grants-in-aid from the National Natural Science Foundation of China(11332003,31370949)the National Key Technology R&D Program of China(2012BAI18B02)the National Key Basic Research Program of China(2012CB619101)。
文摘It is not clear what effects of CD34-and CD133-specific antibody-coated stents have on reendothelialization and in-stent restenosis(ISR)at the early phase of vascular injury.This study aims at determining the capabilities of different coatings on stents(e.g.gelatin,anti-CD133 and anti-CD34 antibodies)to promote adhesion and proliferation of endothelial progenitor cells(EPCs).The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flow-induced shear stress,so that allowing for the growth of the cells on the slides for 48 h.The in vivo experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents(BMS)and gelatin-coated stents.Compared with the anti-CD34 antibody-coated stents,the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR.In conclusion,this study demonstrated that anti-CD133 antibody as a stent coating for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR.
