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BACKGROUND/AIMS: Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo. METHODS: EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis. RESULTS: In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002). CONCLUSION: Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.
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Animals , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Diabetes Mellitus , Cell Movement , Muscle, Skeletal/metabolism , Phosphatidylinositol 3-Kinases , Endothelial Cells , Ischemia , HypoxiaABSTRACT
Objective To observe the protective effect of Shenmajing formula on brain tissue of mice with cerebral ischemic injury and explore the possible mechanism. Methods Thirty SPF-grade C57 BL/6 male mice were randomly divided into model control group, Shenmajing group and nimodipine group, and the animal models of cerebral ischemic injury in mice were prepared by electrocoagulation. The protein expression level in endothelial progenitor cells were detected by Western blot. Results Compared with the model control group, the infarct volume of mice in the Shenmajing group was significantly reduced, and the migration, adhesion and tubule formation ability of endothelial progenitor cells were significantly improved, and the expression level of BDNF protein in endothelial progenitor cells was significantly increased. Conclusion The protective effect of Shenmajing granules on brain tissue of mice with cerebral ischemic injury could be closely related to the regulation of BDNF expression in endothelial progenitor cells and improvement of endothelial progenitor cell function of bone marrow origin.
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Abstract Introduction: Endothelial progenitor cells (EPCs) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme activity may affect the vessel wall and have a role in development of aortic aneurysms. EPCs originate from hematopoietic stem cells and can be enumerated from peripheral blood samples by flow cytometry. In this study, we aimed to evaluate the relation of EPC number and NADPH oxidase enzyme activity in the development of thoracic aortic aneurysm (TAA). Methods: Patients with TAA (n=30) and healthy individuals without TAA (control, n=10) were included in our study. Characterization and enumeration of EPC from peripheral blood samples were performed by flow cytometry with panels including markers of EPCs (CD34/CD133/CD309/CD146/CD144). Additionally, NADPH oxidase enzyme activity (capacity) was also measured by the dihydrorhodamine 123 (DHR 123) test. Results: The enumeration of EPC with CD34+/CD146+ marker showed that the number of mean EPC/106 cells was increased in the patient group (41.5/106 cells), but not in the control group (20.50/105 cells) (P<0.01). Additionally, patients with TAA presented significantly lower NADPH oxidase activity by DHR assay than healthy controls (mean stimulation index: 60.40± 7.86 and 75.10±5.21, respectively) (P<0.01). Conclusion: Our results showed that the number of EPCs is significantly higher in aortic aneurysm patients and may have a role in disease progression. The crosstalk between NADPH oxidase enzyme capacity and EPC number may be useful as a parameter to explain the clinical progression of TAA.
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ABSTRACT Background: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. Objective: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. Methods: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. Results: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). Conclusions: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.
RESUMO Antecedentes: No momento, a etiologia e a patogênese da doença de Moyamoya (DMM) não são completamente claras. Os pacientes geralmente são diagnosticados após eventos cerebrovasculares. Sendo assim, é de grande importância clínica explorar os fatores preditivos de DMM. Objetivo: Este estudo teve como objetivo investigar o nível sérico de CoQ10B, a quantidade de células progenitoras endoteliais (CPE) e a função mitocondrial de CPE em pacientes com DMM. Métodos: Quarenta e um pacientes com DMM e 20 controles saudáveis foram recrutados neste estudo. Aqueles com DMM foram divididos em dois grupos: tipo isquêmico (n=23) e tipo hemorrágico (n=18). Amostras de sangue foram coletadas da veia antecubital e analisadas por CoQ10B Ensaio de Imunoadsorção Enzimática (ELISA) e citometria de fluxo. As medidas da função mitocondrial de CPE incluem taxa de consumo de oxigênio (TCO), potencial de membrana mitocondrial, concentração de Ca2+, atividade de adenosina trifosfatases (ATPase) e nível de espécies reativas de oxigênio (ROS). Resultados: O nível sérico de CoQ10B em pacientes com DMM foi significativamente menor do que em controles saudáveis (p<0,001). O número relativo de CPE em pacientes com MMD foi significativamente maior do que em controles saudáveis (p<0,001). Além disso, a TCO, o potencial de membrana mitocondrial e a atividade ATPase diminuíram e os níveis de Ca2+e ROS aumentaram em pacientes com MMD (p<0,001). Conclusões: Nossos resultados mostraram obviamente diminuição do nível sérico de CoQ10B e aumento do número de CPE em pacientes com DMM em comparação com pacientes saudáveis, e a função mitocondrial de CPE em pacientes com DMM estava anormal.
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Endothelial progenitor cells (EPCs) are progenitor cells possessing vasculogenic potential.The main function of EPCs is to play a role by paracrine angiogenic factors and neuroprotective factors.EPCs also have the ability to differentiate into endothelial cells and integrate themselves into newly formed capillaries.Therefore, EPCs play an important role in vascular repair and neuroprotection.The research on surface markers and functions of EPCs is the basis of EPCs research.A series of clinical trials, animal and cell experiments show that EPCs transplantation and joint transplantation of EPCs and other cells can promote vascular repair and improve retinal function with good safety.EPCs are expected to be an effective treatment for diabetic retinopathy (DR). DR is now defined as a refractory eye disease with retinal neurovascular unit (NVU) injury associated with systemic metabolism anbormality.Change in EPCs count and damage of EPCs function are involved in the occurrence and development of DR.Ophthalmologists should pay attention to the early managing approach of EPCs.Current treatment strategies include transplantation of EPCs, joint transplantation of EPCs with other cells, and regulation of endogenous EPCs.The unique biological characteristics of EPCs provide many possibilities in repairing retinal NVU injury and DR prevention and treatment.This article introduces the latest research progress of EPCs for DR from five aspects including the origin of EPCs, physiological and pathological state, function, treatment strategy and clinical application.At the same time, the existing problems and technical bottlenecks will also be discussed.
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Objective To explore the effect and mechanism of estrogen on endothelial progenitor cells（EPCs）function in diabetic rats. Methods EPCs were isolated from bone marrow of rats and characterized by fluorescence microscopy and flow cytometry. Rat diabetic model was established via streptozotocin induction. The bone marrow was taken to culture EPCs. EPCs of diabetes were incubated with Estrogen 10 nmol/L for 24h. The functions and proliferation of EPCs in vitro were detected. The levels of MnSOD and NO in EPCs and TSP-1 in supernatant were assayed. Results Compared with control group, EPCs proliferation, adhesion and angiogenesis functions were impaired in diabetic rats. The level of MnSOD and NO in diabetic EPCs were significantly decreased, while TSP-1 protein level in the supernatant increased. The above changes can be reversed with estrogen incubation. Conclusion Estrogen improved the EPCs migration and tubule formation in diabetic rats. The mechanism may be related to the reduction of oxidative stress and downregulation of TSP-1 expression in diabetic EPCs.
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Objective:To evaluate the effects of endothelial progenitor cell (EPC)-derived exosomes on neuronal injury induced by oxygen-glucose deprivation and restoration (OGD/R).Methods:HT22 neurons of mice were cultured and divided into 3 groups ( n=30 each) using a random number table method: control group (C group), OGD/R group and OGD/R plus EPC-derived exosome group (OGD/R+ EXO group). Cells in group C were cultured in normal atmosphere.In group OGD/R, the cells were exposed to 94%N 2-1%O 2-5%CO 2 for 6 h in glucose- and serum-free DMEM medium, followed by 24 h restoration of O 2 and glucose in the normal medium.In group OGD/R+ EXO, 20 μg/ml EPC-derived exosomes were added to the culture medium at 24 h before developing the model.EPCs were identified by immunofluorescence staining.Exosomes were identified by Western blot, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Cell viability was measured by CCK-8 assay, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay.The neuronal apoptosis was detected by TUNEL staining, and the apoptosis rate was calculated.The expression of Bax, Bcl-2, caspase-3, and cleaved caspase-3 was determined by Western blot, and cleaved caspase-3/caspase-3 ratio was calculated. Results:The cultured cells were EPCs, and EPC-derived exosomes were successfully extracted.Compared with group C, the cell viability was significantly decreased, the content of MDA was increased, the activity of SOD was decreased, the apoptosis rate was increased, the expression of Bax was up-regulated, the expression of Bcl-2 was down-regulated, and the ratio of cleaved-caspase-3/caspase-3 was increased in group OGD/R and group OGD/R+ EXO ( P<0.05). Compared with group OGD/R, the cell viability was significantly increased, the content of MDA was decreased, the activity of SOD was increased, the apoptosis rate was decreased, the expression of Bax was down-regulated, the expression of Bcl-2 was up-regulated, and the ratio of cleaved-caspase-3/caspase-3 was decreased in group OGD/R+ EXO ( P<0.05). Conclusions:EPC-derived exosomes can reduce OGD/R-induced neuronal injury, which is related to inhibition of oxidative stress and neuronal apoptosis.
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Resumo Fundamento As células progenitoras endoteliais (CPEs) desempenham um papel importante na manutenção da função endotelial. A síndrome metabólica (SM) está associada à disfunção das CPEs. Embora o exercício físico tenha um impacto benéfico na atividade das CPEs, seu mecanismo ainda não está completamente esclarecido. Objetivo O objetivo deste estudo é investigar os efeitos do exercício físico nas funções das CPEs e os mecanismos subjacentes em pacientes com SM. Métodos Os voluntários com SM foram divididos em grupo exercício (n=15) e grupo controle (n=15). Antes e após 8 semanas de treinamento físico, as CPEs foram isoladas do sangue periférico. Foram feitos o ensaio de unidades formadoras de colônias (UFC), o ensaio de formação de tubos, a expressão proteica do óxido nítrico sintase endotelial (eNOS), da fosfatidilinositol-3-quinase (PI3-K) e da proteína quinase B (AKT). Considerou-se um valor de probabilidade <0,05 para indicar significância estatística. Resultados Após 8 semanas, o número de UFCs aumentou significativamente no grupo exercício em comparação com o grupo controle (p<0,05). Além disso, observamos uma diminuição significativa do modelo de avaliação da homeostase da resistência à insulina (HOMA-IR), endotelina-1, proteína C reativa de alta sensibilidade e dos níveis de homocisteína no grupo exercício. A intervenção com exercícios também pode aumentar a capacidade de formação de tubos de CPEs e aumentar o nível de fosforilação de eNOS, PI3-K e AKT. Conclusão O exercício físico aprimorou as funções das CPEs. O mecanismo pode estar relacionado ao exercício, ativando a via PI3-K/AKT/eNOS.
Abstract Background Endothelial progenitor cells (EPCs) play an important role in maintaining endothelial function. Metabolic syndrome (MetS) is associated with EPC dysfunction. Although physical exercise has a beneficial impact on EPC activity, its mechanism is not completely clear yet. Objective The purpose of this study is to investigate the effects of physical exercise on the functions of EPCs and the underlying mechanisms in patients with MetS. Methods Volunteers with MetS were divided into exercise group (n=15) and control group (n=15). Before and after 8 weeks exercise training, EPCs were isolated from peripheral blood. Colony forming unit (CFU) assay, tube-formation assay, the protein expression of endothelial nitric oxide synthase (eNOS), phosphatidylinositol-3-kinase (PI3-K) and protein kinase B (AKT) were determined. A probability value <0.05 was considered to indicate statistical significance. Results After 8 weeks, the number of CFUs was significantly increased in the exercise group compared to the control group (p<0.05). In addition, we observed a significant decrease of homeostasis model assessment for insulin resistance (HOMA-IR), endothelin-1, high-sensitive C-reactive protein, and homocysteine levels in the exercise group. Exercise intervention could also enhance tube-formation capacity of EPCs and increase phosphorylation level of eNOS, PI3-K and AKT. Conclusion Physical exercise enhanced the functions of EPCs. The mechanism may be related to exercise, activating the PI3-K/AKT/eNOS pathway.
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Humans , Metabolic Syndrome/therapy , Endothelial Progenitor Cells , Phosphorylation , Exercise , Cells, Cultured , Nitric Oxide Synthase Type III/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Nitric OxideABSTRACT
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.
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BACKGROUND: Studies have shown that mesenchymal stem cells can participate in the repair of wound injury caused by diabetes, but the high glucose environment obviously inhibits the function of mesenchymal stem cells and the effect of transplantation. OBJECTIVE: To observe the effect of conditioned medium of bone marrow mesenchymal stem cells intervened by rosiglitazone on the proliferation and migration of endothelial progenitor cells in high glucose environment. METHODS: (1) The bone marrow mesenchymal stem cells from the logarithmic growth period were cultured in three groups. The normal group was cultured with alpha-MEM medium containing 10% fetal bovine serum. The high glucose group was cultured with alpha-MEM medium containing 10% fetal bovine serum and 25 mmol/L glucose. The rosiglitazone group was cultured with alpha-MEM medium containing 10% fetal bovine serum, 25 mmol/L glucose and 10 μmol/L rosiglitazone. After 48 hours of culture, the culture supernatant was extracted as conditioned medium. The levels of vascular endothelial growth factor and matrix cell derived factor 1 in conditioned medium were detected by ELISA. (2) The endothelial progenitor cells from the logarithmic growth period were divided into three groups. The control group was cultured with the EGM-2 MV medium containing 10% fetal bovine serum. The model group was cultured with the EGM-2 MV medium containing 10% fetal bovine serum, 30 mmol/L glucose and conditioned medium of the high glucose group. The experimental group was cultured with EGM-2 MV medium containing 10% fetal bovine serum, 30 mmol/L glucose and conditioned medium of the rosiglitazone group. After 24 hours of culture, the ability of cell proliferation and migration was detected. RESULTS AND CONCLUSION: (1) The levels of vascular endothelial growth factor and matrix cell derived factor 1 in the conditioned medium of high glucose group were significantly lower than that of the normal group (P < 0.05). The levels of vascular endothelial growth factor and matrix cell derived factor 1 in the conditioned medium of the rosiglitazone group were significantly higher than in the high glucose group (P < 0.05). (2) The proliferation and migration ability of endothelial progenitor cells in the model group was lower than that in the control group (P < 0.05). The proliferation and migration ability of endothelial progenitor cells in the experimental group was higher than that in the model group (P < 0.05). (3) It is suggested that the conditioned medium of rosiglitazone intervened bone marrow mesenchymal stem cells can promote the proliferation and migration of endothelial progenitor cells.
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Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China. In this study, we investigated the protective effect and underlying mechanisms GXB in type II diabetes with acute myocardial ischemia (T2DM-AMI) rats. We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells (EPCs) apoptosisviaactivating PI3K (phosphatidyl inositol 3-kinase)/Akt (serine/threonine protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling. Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of type II diabetes mellitus (T2DM) and coronary ligation to induce acute myocardial infarction (AMI). Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination. The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry. Target mRNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis. The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose, muscular enzymes, and blood lipids, and reduced oxidative stress. Furthermore, EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased mRNA and protein levels of PI3K, Akt, and eNOS compared to the controls. Conversely, T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis, combined with increased mRNA and protein levels of PI3K, Akt, and eNOS compared to those of untreated T2DM-AMI rats. Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.
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Moyamoya disease (MMD) is currently thought to involve endothelial progenitor cells (EPCs). We investigated whether superparamagnetic iron oxide (SPIO) can be used to label EPCs. Mononuclear cells from 10 moyamoya disease patients were isolated, and cluster of differentiation 133 (CD133) positive cells sorted by magnetic-activated cell sorting were cultured in vitro. The positive rates of CD133, vascular endothelial growth factor receptor (VEGFR)-2, and cluster of differentiation 34 (CD34) were detected by flow cytometry. The cells were co-cultured with fluorescence labeled Dil-acetylated-low-density lipoprotein (Dil-ac-LDL) and Ulex europaeus agglutinin-1 (UEA-1) to observe the endocytosis of Dil-ac-LDL and binding to UEA-1. Prussian blue staining and transmission electron microscopy were used to observe the endocytosis of different SPIO concentrations in EPCs, and CCK-8 was used to detect proliferation of cells transfected with different concentrations of SPIO. T2 weighted imaging (T2WI) signals from magnetic resonance imaging after SPIO endocytosis were compared. Positive rates of CD133, VEGFR-2, and CD34 on sorted mononuclear cells were 68.2±3.8, 57.5±4.2, and 36.8±6.5%, respectively. The double-positive expression rate of CD34 and VEGFR-2 was 19.6±4.7%, and 83.1±10.4% of cells, which showed the uptake of Dil-ac-LDL and binding with UEA-1. The labeling efficiencies of SPIO at concentrations of 25 and 50 μg/mL were higher than for 12.5 μg/mL. The proliferation of cells was not influenced by SPIO concentrations of 12.5 and 25 μg/mL. After labeling, the T2WI of EPCs was reduced. The concentration of 25 μg/mL SPIO had high labeling efficiency detected by magnetic resonance imaging (MRI) without decreased EPCs viability.
Subject(s)
Humans , Male , Adult , Middle Aged , Magnetite Nanoparticles , Endothelial Progenitor Cells , Moyamoya Disease/diagnostic imaging , Magnetic Resonance Imaging , Ferric Compounds , Cells, Cultured , Vascular Endothelial Growth Factor A , Metal NanoparticlesABSTRACT
Objective To study the protective effects and preliminary mechanisms of endothelial progenitor cells-derived microvesicles (EPC-MVs) on hypoxic-ischemic brain damage (HIBD) in newborn rats by using the HIBD model.Method Rat endothelial progenitor cells (EPCs) were cultured and microvesicles were extracted from EPCs culture medium by ultracentrifugation.A total of 60 neonatal SD rats were randomly assigned into control group,HIBD group,saline group and EPC-MVs group.The HIBD model was prepared in HIBD group,saline group and EPC-MVs group.After the preparation of the HIBD model,rats in saline group and EPC-MVs group received intraventricular injection with saline and EPC-MVs,respectively.After 72 hours,the rats were sacrificed for brain tissue,cerebral infarction was detected by TTC staining,vascular endothelial growth factor (VEGF) mRNA was tested by real-time PCR,protein western blot was used to detect changes in VEGF protein expression.Result Cells extracted and cultured from the spleen of 12-week-old SD rats were confirmed as EPCs by morphology and flow cytometry.EPC-MVs isolated by high-speed centrifugation from EPCs culture supernatant met the morphological characteristics of microvesicles by transmission electron microscopy.The infarcted brain tissue was not detected in the control group.The cerebral infarction volume ratios of HIBD group,saline group and EPC-MVs group were (80.3 ± 6.3) ％,(77.9 ± 8.9) ％,(35.2 ± 7.7) ％,respectively.The infarct volume of EPC-MVs group was significantly lower than that of HIBD group and saline group (P ＜ 0.001).The expression of VEGF mRNA and protein in HIBD group,saline group and EPC-MVs group were higher than those in control group (P ＜0.001).Among them,EPC-MVs group had the most significant increase,compared with the other three experimental groups,and the difference was statistically significant (P ＜ 0.001).There was no significant difference between saline group and HIBD group in the expression of VEGF mRNA and protein (P ＞ 0.05).Conclusion Intraventricular injection of EPC-MVs can attenuate HIBD in neonatal rats,and the mechanism may be related to up-regulation of VEGF expression.
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BACKGROUND: With the constant development of current society, traumatic bone injury caused by the traffic and other accidents becomes more and more common. Bone defect scope is increasingly extend, and the treatment results in the long cycle, the high cost, and the uncontrolled effect, accompanied with infections, bone nonunion and other complications, which not only causes the painfulness of the patient physically and mentally, but also is a difficult problem and challenge for orthopedic surgeons at the same time. OBJECTIVE: To analyze the advantages and disadvantages of traditional treatments and their latest progress, and focus on the research progress and advantages of tissue engineering technology in treating bone defect. METHODS: The author took “bone defect, bone transplantation, tissue engineering, induced membrane technology, bone transfer technology, endothelial progenitor cells, 3 D printing technology” as the key words, and data were summarized by searching CNKI, Wanfang and Pub Med databases. Totally 120 related literatures were retrieved. Through reading the title, abstract and part of the literature content, the outdated, ambiguous and repetitive literatures were excluded. Finally, 49 literatures meeting the inclusion criteria were selected for review. RESULTS AND CONCLUSION:(1) Traditional bone defect treatment has certain defects. The emergence of bone tissue engineering technology is expected to become one of the most effective ways for bone defect.(2) Seed cells have good osteogenic properties and can secrete some important factors.(3) Scaffold material can provide mechanical strength for patients in early stage, and has advantages of good biocompatibility, bone induction, and controllable degradation.(4) The urgent problem of vascularization is also being solved gradually, which can bring good news to the patients with bone defect.
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BACKGROUND: Fracture is a common orthopedic disease in clinic. Although most fractures can heal by primary bone healing through surgical treatments, such as rigid internal fixation, malunion is liable to occur in some circumstances, eventually leading to bone defects. Neovascularization at the bone defect site plays a vital role in bone healing. Based on the pro-angiogenic ability of endothelial progenitor cells (EPCs), its capacity for bone regeneration and repair has gradually become the focus of attention. OBJECTIVE: To review the use of EPCs transplantation to promote vasculogenesis and osteogenesis in bone defects. METHODS: With the key words of “endothelial progenitor cells (EPCs), angiogenesis, vasculogenesis, therapy/treatment, bone defect” in Chinese and English, we performed a computer-based search in CNKI, WanFang and PubMed databases for relevant articles published from 1986 to 2019. Finally, 58 eligible articles were included in result analysis. During the literature retrieval, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS AND CONCLUSION: Bone defects can promote the activation and homing of EPCs. EPCs can promote vasculogenesis and further trigger bone regeneration. There are still some problems to be solved before the application of EPCs in the treatment of bone defects. More experiments need to be carried out to investigate the exact mechanism of EPCs in vasculogenesis. More clinical trials are warranted, providing data support for future clinical applications and giving better treatment to patients disabled by bone defects.
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BACKGROUND: Mesenchymal stem cell transplantation has been proved to be effective for ulcerative colitis, while the effect of endothelial progenitor cells in ulcerative colitis treatment is still unknown. They are both promising cells for tissue engineering, which can be used for cell transplantation. OBJECTIVE: To explore whether co-transplantation of endothelial progenitor cells and adipose mesenchymal stem cells can relieve ulcerative colitis in a mouse model. METHODS: C57BL/6J mice were randomly divided into six groups (n=24 per group): co-transplantation group, mesenchymal stem cell transplantation group, endothelial progenitor cell transplantation group, glucocorticoid treatment group, transplantation control group and normal control group. Murine ulcerative colitis model was established in all groups except for the normal control group. At 7 and 10 days after modeling, transplantation groups were respectively injected via tail vein with adipose mesenchymal stem cells and/or endothelial progenitor cells, glucocorticoid or PBS. Mice were sacrificed at 12 days after modeling. Colon length, disease activity index, histological score and the serum level of tumor necrosis factor-α were compared between groups. RESULTS AND CONCLUSION: Treatment with glucocorticoid was significantly effective for ulcerative colitis relative to the transplantation control group (P 0.05). Co-transplantation of adipose mesenchymal stem cells and endothelial progenitor cells was better than the other treatments, which significantly improved the shortening of the colon, disease activity index, histological score, and serum level of tumor necrosis factor-α.
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70% to 80% of people with diabetes died from cardiovascular complications, which had become the leading cause of death in diabetic patients. Cardiovascular complications in diabetic patients are mainly associated with vascular endothelial dysfunction and poor neovascularization. Its important influencing factors are changes in the number of endothelial progenitor cells and dysfunction. Hyperglycemia in diabetic patients can cause endothelial progenitor cell dysfunction, inhibit its proliferation ability, angiogenesis ability and paracrine effect. In order to provide research ideas for the prevention and treatment of cardiovascular complications in diabetic patients, this article aims to review the relevant mechanism of the effect of hyperglycemia on the number and function of endothelial progenitor cells in patients with diabetes, and the application of endothelial progenitor cells in the treatment of diabetic cardiovascular disease.
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Endothelial progenitor cells (EPC) are stem cells derived from bone marrow and peripheral blood, which could proliferate and differentiate into endothelial cells and participate in repair after tube injury. Studies have shown that the improving function of diabetic EPC could prevent and reduce the occurrence of diabetic complications. The research progress in improving the function of EPC in recent years and the improvement of function in the development of diabetes were reviewed in order to provide new ideas for the treatment of diabetes.
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Objective:To observe protective effect of Danggui Buxuetang (DBT) on oxidative stress injury of mouse bone marrow-derived endothelial progenitor cells (EPCs) against induced by hydrogen peroxide (H2O2). Method:Monocytes from bone marrow of mice were obtained by density gradient centrifugation, and EPCs were obtained by specific culture medium. The experiment was divided into blank group，model group，DBT group (100，200，400 mg·L-1). Methyl thiazolyl tetrazolium（MTT） assay was used to determine the survival rate of EPCs and establish the cell injury model induced by H2O2. MTT，transwell chamber，matrigel and superoxide fluorescent anion probe (DHE) were used to detect the proliferation，migration，in vitro angiogenesis and ROS level，detection of autophagy by Western blot. Result:Compared with blank group，the proliferation ability，migration ability，the number of lumens and the length of tubule branches of EPCs in the model group were significantly reduced (P<0.01)，the level of intracellular reactive oxygen species （ROS） was significantly increased (P<0.01)，the expression of p62，the light chain microtubule associated protein 1 protein light chain 3 Ⅱ type （LC3-Ⅱ） protein of microtubule associated protein 1，was significantly increased (P<0.01). Compared with model group，DBT group increased the ability of cell proliferation and migration （P<0.01）. In addition，DBT increased the expression of LC3-Ⅱ protein in a concentration dependent manner (P<0.01)，and decreased the expression of p62 protein (P<0.01). Conclusion:DBT can improve the autophagy level of EPCs under oxidative stress, promote the proliferation, migration and angiogenesis of injured EPCs, and protect the biological function of EPCs under oxidative stress.
ABSTRACT
Endothelial progenitor cells (EPCs) play an important role in diabetic vascular complications. A large number of studies have revealed that some clinical antihyperglycemics can improve the complications of diabetes by regulating the function of EPCs. Metformin can improve EPCs function in diabetic patients by regulating oxidative stress level or downstream signaling pathway of adenosine monophosphate activated protein kinase; Pioglitazone can delay the aging of EPCs by regulating telomerase activity; acarbose, sitagliptin and insulin can promote the proliferation, migration and adhesion of EPCs. In addition to lowering blood glucose, the effects of antihyperglycemics on EPCs may also be one of the mechanisms to improve the complications of diabetes. This article reviews the research progress on the regulation of EPC proliferation and function by antihyperglycemics.