Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPC...Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPCs） from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-β Ⅲ-tubulin （Tuj1） and 84% expressed astrocyte specific marker-fibrillary acidic protein （GFAP）. In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.展开更多
Background Endothelial progenitor cells （EPCs） have been used in both experimental studies and clinical treatments of limb ischemia, as well as in the construction of engineered vascular tissue. The objective of thi...Background Endothelial progenitor cells （EPCs） have been used in both experimental studies and clinical treatments of limb ischemia, as well as in the construction of engineered vascular tissue. The objective of this study was to investigate the effects of transplanted bone marrow-derived EPCs on the vein microenvironment in a rat model of chronic vein thrombosis. Methods Mononuclear cells were isolated from the bone marrow of immature rats by density gradient centrifugation, cultured, and then transplanted into experimentally induced thrombi into infedor vena cava through the femoral vein. Vascular endothelial growth factor （VEGF）, angiopoietin-1 （ANG-1） and monocyte chemotactic protein-1 （MCP-1） mRNA and protein expression levels were measured by real-time quantitative polymerase chain reaction and Western blotting of thrombi and adjacent caval walls 28 days post-transplantation. Results Levels of VEGF, ANG-1, and MCP-1 mRNA in EPC-transplanted thrombi were 100%, 230.7%, and 212.5% of levels detected in the sham-operated group （P〈0.01）, and 99.9%, 215.4%, and 177.8% of levels detected in the experimental control group （P〈 0.01）. VEGF, ANG-1 and MCP-1 protein levels exhibited a similar trend. Conclusions Transplanted bone marrow-derived EPCs appear to alter the vein microenvironment in experimentally induced chronic vein thrombosis by upregulating cytokines associated with thrombic organization and recanalization.展开更多
Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of fo...Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.展开更多
In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types. The available data indeed strongly suggest that most com...In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types. The available data indeed strongly suggest that most combined hepatocellular-cholangiocarcinomas arise from hepatic progenitor cells that retained their potential to differentiate into the hepatocytic and biliary lineages. Hepatic progenitor cells could also be the basis for some hepatocellular carcinomas and hepatocellular adenomas, although it is very difficult to determine the origin of an individual hepatocellular carcinoma. There is currently not enough data to make statements regarding a hepatic progenitor cell origin of cholangiocarcinoma. The presence of hepatic progenitor cell markers and the presence and extent of the cholangiocellular component are factors that are related to the prognosis of hepatocellular carcinomas and combined hepatocellular- cholangiocarcinomas, respectively.展开更多
Dendritic cells(DC)are crucial cells of the immune system,and bridged the essential connection between innate and adaptive immunity.They reside in the periphery as sentinels where they take up antigens.Upon activation...Dendritic cells(DC)are crucial cells of the immune system,and bridged the essential connection between innate and adaptive immunity.They reside in the periphery as sentinels where they take up antigens.Upon activation, they migrate to lymphoid organs and present there the processed antigens to T cells,thereby activating them and eliciting a potent immune response.Dendritic cells are bone marrow-derived cells,still big controversies exist about their in vivo development.In vitro,DC can be generated from multiple precursor cells,among them lymphoid and myeloid committed progenitors.Although it remains unknown how DC are generated in vivo, studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine.Therefore,in this review,we present current protocols for the generation of DC from precursors in vitro.We will do this for the mouse system,where most research occurs and for the human system,where research concentrates on implementing DC biology in disease treatments.Cellular & Molecular Immunology.2005;2(1):28-35.展开更多
Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of p...Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury.Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role.Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk.In this review,we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension,obstructive sleep-apnea syndrome,obesity,diabetes mellitus,peripheral arterial disease,coronary artery disease,pulmonary hypertension,and heart failure.Recent studies have introduced the novel concept that physical activity,either performed as a single exercise session or performed as part of an exercise training program,results in a significant increase of circulating EPCs.In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.展开更多
The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabeti...The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.展开更多
Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leu...Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.展开更多
Objective： To observe the effect of Xuefu Zhuyu Decoction （血府逐瘀汤）-containing serum （XFZYD-CS） on endothelial progenitor cell （EPC） tube formation in vitro. Methods： Mononuclear cells from rat bone marrow ...Objective： To observe the effect of Xuefu Zhuyu Decoction （血府逐瘀汤）-containing serum （XFZYD-CS） on endothelial progenitor cell （EPC） tube formation in vitro. Methods： Mononuclear cells from rat bone marrow were prepared in a Ficoll density gradient centrifuge. EPCs were separated by the differential attachment method, and observed with inverted microscope for the effect of XFZYD-CS on EPC tube formation. Results： After one day, EPCs exposed to the serum containing 5%, 10% and 15% XFZYD-CS formed typical tubes or vessel networks. The tube formation time was two days ahead of the control group and the size of most tubes in the serum groups was smaller than in the control group. Conclusion： XFZYD-CS could induce EPC angiogenesis and hasten tube formation, especially in capillary vessels. The study provides experimental evidence for the plausibility of Xuefu Zhuyu Decoction in the treatment of ischemic diseases.展开更多
Background Cell-based vascular therapies of endothelial progenitor cells （EPCs） mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was design...Background Cell-based vascular therapies of endothelial progenitor cells （EPCs） mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs （hUCB-EPCs） in rat with acute myocardial infarction. Methods Human umbilical cord blood （hUCB） mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1＇-dioctadecyl-3,3,3＇,3＇-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein （DiI-Ac-LDL） and fluorescein isothiocyanate-conjugated Ulex europaeus lectin （FITC-UEA-I）. The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density （CAD） was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen （HNA） and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen （PCNA）, platelet endothelial cell adhesion molecule （PECAM） and vascular endothelial growth factor （VEGF） were detected to investigate the underlying mechanisms of cell differentiation and revascularization. Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted ra展开更多
This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myoc...This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myocardial infarction （AMI）, and to investigate the relationships between these cytokines and early EPCs. Early EPCs, de- fined as CD133＋, KDR＋, and CD34~ cells, were quantified by flow cytometry. The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls （P 〈 0.05）. Plasma apelin levels were inversely correlated with Gensini score and early EPCs （both P 〈 0.01）. Early EPCs, VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h. The trend in the change of early EPCs was proportionally correlated with that of VEGF （P 〈 0.05）. AMI patients exhibited in- creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.展开更多
Background Enhanced external counterpulsation （EECP） improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor ...Background Enhanced external counterpulsation （EECP） improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34^＋, CD29^＋, and CD106^＋. Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups： normal diet （control, n=6）, hypercholesterolemic diet （CHOL, n=-6）, hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor （rhG-CSF） （rhG-CSF, n=6）, and hypercholesterolemic diet with EECP treatment （EECP, n=6）. EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor （VEGF） and granulocyte colony-stimulating factor （G-CSF）, peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor l a （SDF-1α） in porcine myocardium were assessed, respectively. Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 （（38.3±5.6） pg/ml at week 15 vs （26.2±3.7） pg/ml at week 12, P 〈0.05, and （46.9±6.1） pg/ml at week 18 vs （26.2±3.7） pg/ml at week 12, P 〈0.01）. The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days （（150±13.9） pg/ml at week 18 vs （24.8±5.4） pg/ml at week 12, P 〈0.01）. Compared to other groups and other time points, progenitor celt counts increased significantly after 2-hour EECP treatment （108±13 vs 26±6 per 10^5 leukocytes, P 〈0.01）, but not at week 18. The prog展开更多
Background There are numerous articles on the endothelial progenitor cells （EPCs） in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome （ACS） are still uncertain. H...Background There are numerous articles on the endothelial progenitor cells （EPCs） in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome （ACS） are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients. Methods Patients were enrolled with admitted ACS （n=25） and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease （CAD） controls. EPCs were defined as CD34＋/CD133＋/VEGFR-2＋ and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit （CFU）, proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 （MMP-9） was detected in all patients as well. Results The two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects （15.6±2.7 vs. 6.0±0.8 /100 000 events, P 〈0.01）. CFU was not statistically different between the two groups （10.8±2.9 vs. 8.2±1.8, number/well, P 〉0.05）. Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation （0.498±0.035 vs. 0.895±0.067, OD value, P〈0.01） and migration capacity （20.5±3.4 vs. 30.7±4.3, number/well, P 〈0.01） compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group （（18.3±2.. 1 ）% vs. （7.8±0.4）%, P 〈0.01）. Conclusions Patients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects.展开更多
The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial c...The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.展开更多
Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are invo...Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are involved in angiogenesis and maintenance of vascular integrity following HLI.On the other side,it has been proved that Astragalus polysaccharide （APS） could promote angiogenesis.In the present study,we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin （STZ）-induced diabetes.Methods Rats （n=110） were randomly assigned to the following groups：sham group,ischemia group,APS group,EPCs group and APS＋EPCs group.APS,EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction,and 6 rats were assessed by angiography at 28 days after induction of HLI,6 rats were sacrificed at the same time point to take histological studies,biochemical tests were also performed at that point in the rest rats.Results APS or EPCs treatment induced an increase,respectively,in the protein expression of vascular endothelial growth factor （VEGF） （36.61%,61.59%）,VEGF receptor-1 （VEGFR-1） （35.50%,57.33%）,VEGFR-2 （31.75%,41.89%）,Angiopoietin-1 （Ang-1） （37.57%,64.66%） and Tie-2 （42.55%,76.94%） （P 〈0.05）,after HLI injury.And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats,through elevating protein expression of VEGF （99.67%）,VEGFR-1 （105.33%）,VEGFR2 （72.05%）,Ang-1 （114.30%） and Tie-2 （111.87%） （P〈0.05）.Similarly,mRNA expression of VEGF,VEGFR-1,VEGFR2,Ang-1,Tie-2 also show similar trends as well as protein expression （P〈0.05）.Conclusion APS or EPCs could enhance angiogenesis,and the combined treatment leads to better effort,at least,partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.展开更多
Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilica...Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells （EPCs） and decellularized valve scaffolds. Methods Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 × 10^6 cells/cm^2 and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction （RT-PCR） analysis for the expression of endothelial nitric oxide synthase （eNOS） and tissue-type plasminogen activator （t-PA）.Results EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor （vWF） and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 （UEA-1）, and took up Dil-labeled low density lipoprotein （Dil-Ac-LDL）. After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolay展开更多
AIM To investigate the significance of endothelial progenitor cells (EPCs) in predicting severe acute pancreatitis (SAP). METHODS We recruited 71 patients with acute pancreatitis (AP) and excluded 11 of them; finally,...AIM To investigate the significance of endothelial progenitor cells (EPCs) in predicting severe acute pancreatitis (SAP). METHODS We recruited 71 patients with acute pancreatitis (AP) and excluded 11 of them; finally, cases of mild acute pancreatitis (MAP) (n = 30) and SAP (n = 30), and healthy volunteers (n = 20) were internalized to investigate levels of EPCs, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), fibrinogen (FIB) and white blood cells (WBC) in peripheral blood. RESULTS The levels of TNF-alpha, WBC, FIB and CRP were higher both in SAP and MAP cases than in healthy volunteers (P < 0.05, all). Interestingly, the level of EPCs was higher in SAP than MAP (1.63% +/- 1.47% vs 6.61% +/- 4.28%, P < 0.01), but there was no significant difference between the MAP cases and healthy volunteers (1.63% +/- 1.47% vs 0.55% +/- 0.54%, P > 0.05). Receiver operating characteristics curve (ROC) showed that EPCs, TNF-alpha, CRP and FIB were significantly associated with SAP, especially EPCs and CRP were optimal predictive markers of SAP. When the cut-off point for EPCs and CRP were 2.26% and 5.94 mg/dL, the sensitivities were 90.0% and 73.3%, and the specificities were 83.3% and 96.7%. Although, CRP had the highest specificity, and EPCs had the highest sensitivity and highest area under the curve value (0.93). CONCLUSION Data suggest that EPCs may be a new biological marker in predicting SAP.展开更多
Objective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases. Data sources The data used in this review were mainly from Medline and PubMed for relevant English lang...Objective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007. The search term was ＂endothelial progenitor cells＂. Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used. Results Progenitor cells in bone marrow, peripheral blood and adventitia can differentiate into mature endothelial cells （ECs）. The progenitor cells, which express certain surface markers including AC133, CD34 and KDR, enable restoration of the microcirculation and ECs when injury or ischaemia occurs. Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development. Moreover, their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors. Impairment of the progenitor cells might limit the regenerative capacity, even lead to the development of atherosclerosis or other vascular diseases. Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases. However, many challenges remain in understanding differentiation of endothelial progenitor cells, their mobilization and revascularization.展开更多
Objective Sevoflurane is widely used in pediatric anesthesia and former studies showed that it causes neurodegeneration in the developing brain. The present study was carried out to investigate the effects of sevoflur...Objective Sevoflurane is widely used in pediatric anesthesia and former studies showed that it causes neurodegeneration in the developing brain. The present study was carried out to investigate the effects of sevoflurane on neurogenesis, neurodegeneration and behavior. Methods We administered 5-bromodeoxyuridine, an S-phase marker, before, during, and after 4 h of sevoflurane given to rats on postnatal day 7 to assess dentate gyrus progenitor proliferation and Fluoro-Jade staining for degeneration. Spatial reference memory was tested 2 and 6 weeks after anesthesia. Results Sevoflurane decreased progenitor proliferation and increased cell death until at least 4 days after anesthesia. Spatial reference memory was not affected at 2 weeks but was affected at 6 weeks after sevoflurane administration. Conclusion Sevoflurane reduces neurogenesis and increases the death of progenitor cells in developing brain. This might mediate the lateonset neurocognitive outcome after sevoflurane application.展开更多
基金This work was supported by grants from the National Basic Research Program of China (No.973, 2001CB510104), National Natural Science Foundation of China (No. 30460141), and Program for New Century Excellent Talents in University (2005).
文摘Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPCs） from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-β Ⅲ-tubulin （Tuj1） and 84% expressed astrocyte specific marker-fibrillary acidic protein （GFAP）. In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.
基金This work was supported by a grant from the Project of Natural Science Foundation of Jiangsu Province (No.BK2007055).
文摘Background Endothelial progenitor cells （EPCs） have been used in both experimental studies and clinical treatments of limb ischemia, as well as in the construction of engineered vascular tissue. The objective of this study was to investigate the effects of transplanted bone marrow-derived EPCs on the vein microenvironment in a rat model of chronic vein thrombosis. Methods Mononuclear cells were isolated from the bone marrow of immature rats by density gradient centrifugation, cultured, and then transplanted into experimentally induced thrombi into infedor vena cava through the femoral vein. Vascular endothelial growth factor （VEGF）, angiopoietin-1 （ANG-1） and monocyte chemotactic protein-1 （MCP-1） mRNA and protein expression levels were measured by real-time quantitative polymerase chain reaction and Western blotting of thrombi and adjacent caval walls 28 days post-transplantation. Results Levels of VEGF, ANG-1, and MCP-1 mRNA in EPC-transplanted thrombi were 100%, 230.7%, and 212.5% of levels detected in the sham-operated group （P〈0.01）, and 99.9%, 215.4%, and 177.8% of levels detected in the experimental control group （P〈 0.01）. VEGF, ANG-1 and MCP-1 protein levels exhibited a similar trend. Conclusions Transplanted bone marrow-derived EPCs appear to alter the vein microenvironment in experimentally induced chronic vein thrombosis by upregulating cytokines associated with thrombic organization and recanalization.
基金Supported by The National Medical Research Council,Singa-pore,No.NMRC/NIG/1038/2010the National University Health System Clinician Scientist Program(NCSP)from the Cli-nician Scientist Unit,Yong Loo Lin School of Medicine,National University of Singapore
文摘Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.
文摘In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types. The available data indeed strongly suggest that most combined hepatocellular-cholangiocarcinomas arise from hepatic progenitor cells that retained their potential to differentiate into the hepatocytic and biliary lineages. Hepatic progenitor cells could also be the basis for some hepatocellular carcinomas and hepatocellular adenomas, although it is very difficult to determine the origin of an individual hepatocellular carcinoma. There is currently not enough data to make statements regarding a hepatic progenitor cell origin of cholangiocarcinoma. The presence of hepatic progenitor cell markers and the presence and extent of the cholangiocellular component are factors that are related to the prognosis of hepatocellular carcinomas and combined hepatocellular- cholangiocarcinomas, respectively.
文摘Dendritic cells(DC)are crucial cells of the immune system,and bridged the essential connection between innate and adaptive immunity.They reside in the periphery as sentinels where they take up antigens.Upon activation, they migrate to lymphoid organs and present there the processed antigens to T cells,thereby activating them and eliciting a potent immune response.Dendritic cells are bone marrow-derived cells,still big controversies exist about their in vivo development.In vitro,DC can be generated from multiple precursor cells,among them lymphoid and myeloid committed progenitors.Although it remains unknown how DC are generated in vivo, studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine.Therefore,in this review,we present current protocols for the generation of DC from precursors in vitro.We will do this for the mouse system,where most research occurs and for the human system,where research concentrates on implementing DC biology in disease treatments.Cellular & Molecular Immunology.2005;2(1):28-35.
文摘Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury.Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role.Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk.In this review,we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension,obstructive sleep-apnea syndrome,obesity,diabetes mellitus,peripheral arterial disease,coronary artery disease,pulmonary hypertension,and heart failure.Recent studies have introduced the novel concept that physical activity,either performed as a single exercise session or performed as part of an exercise training program,results in a significant increase of circulating EPCs.In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.
文摘The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.
文摘Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.
基金Supported by the National Natural Science Foundation of China (No.30772877)Basic Research Fund of China Academy of Chinese Medical Sciences(No.ZZ2006039)Fujian Academy of Integrative Medicine Foundation(No.3000-905010805)
文摘Objective： To observe the effect of Xuefu Zhuyu Decoction （血府逐瘀汤）-containing serum （XFZYD-CS） on endothelial progenitor cell （EPC） tube formation in vitro. Methods： Mononuclear cells from rat bone marrow were prepared in a Ficoll density gradient centrifuge. EPCs were separated by the differential attachment method, and observed with inverted microscope for the effect of XFZYD-CS on EPC tube formation. Results： After one day, EPCs exposed to the serum containing 5%, 10% and 15% XFZYD-CS formed typical tubes or vessel networks. The tube formation time was two days ahead of the control group and the size of most tubes in the serum groups was smaller than in the control group. Conclusion： XFZYD-CS could induce EPC angiogenesis and hasten tube formation, especially in capillary vessels. The study provides experimental evidence for the plausibility of Xuefu Zhuyu Decoction in the treatment of ischemic diseases.
基金The study was supported by grants from the Research Grant of the Department of Guangdong Science and Technology （No. 2003C30603）, Natural Science Foundation of Guangdong Province （No. 5001680） and National Natural Science Foundation of China （No. 30770896）.Acknowledgement： The authors would like to thank Mr. DAI Gang and Dr. CHEN Long for their technical assistance in cell isolation, animal model and confocal microscopy.
文摘Background Cell-based vascular therapies of endothelial progenitor cells （EPCs） mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs （hUCB-EPCs） in rat with acute myocardial infarction. Methods Human umbilical cord blood （hUCB） mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1＇-dioctadecyl-3,3,3＇,3＇-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein （DiI-Ac-LDL） and fluorescein isothiocyanate-conjugated Ulex europaeus lectin （FITC-UEA-I）. The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density （CAD） was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen （HNA） and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen （PCNA）, platelet endothelial cell adhesion molecule （PECAM） and vascular endothelial growth factor （VEGF） were detected to investigate the underlying mechanisms of cell differentiation and revascularization. Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted ra
基金supported by the program (No. CX10B_421Z to Jiaxin Ye) for Postgraduate Research Innovation in Universities of Jiangsu Provincethe grants (No. 81070195) and (No. 81000055) from Chinese National Science Fund of China (all to Biao Xu)grant (No.KF200938 to Lina Kang) from Jiangsu Province
文摘This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myocardial infarction （AMI）, and to investigate the relationships between these cytokines and early EPCs. Early EPCs, de- fined as CD133＋, KDR＋, and CD34~ cells, were quantified by flow cytometry. The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls （P 〈 0.05）. Plasma apelin levels were inversely correlated with Gensini score and early EPCs （both P 〈 0.01）. Early EPCs, VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h. The trend in the change of early EPCs was proportionally correlated with that of VEGF （P 〈 0.05）. AMI patients exhibited in- creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.
基金This study was supported by grants from tile China National 10th Five-year Key Research Project of Science （No. 2001BA706B-07） and National Natural Science Foundation of China （No. 30127001）.Acknowledgement： The authors would like to thank FAN Dian-qiu, FENG Min-zhe, LIN Gui-fan, QIAN Yue-tao, DAI Gang and LIAN Lu-guang for their technical supports.
文摘Background Enhanced external counterpulsation （EECP） improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34^＋, CD29^＋, and CD106^＋. Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups： normal diet （control, n=6）, hypercholesterolemic diet （CHOL, n=-6）, hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor （rhG-CSF） （rhG-CSF, n=6）, and hypercholesterolemic diet with EECP treatment （EECP, n=6）. EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor （VEGF） and granulocyte colony-stimulating factor （G-CSF）, peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor l a （SDF-1α） in porcine myocardium were assessed, respectively. Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 （（38.3±5.6） pg/ml at week 15 vs （26.2±3.7） pg/ml at week 12, P 〈0.05, and （46.9±6.1） pg/ml at week 18 vs （26.2±3.7） pg/ml at week 12, P 〈0.01）. The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days （（150±13.9） pg/ml at week 18 vs （24.8±5.4） pg/ml at week 12, P 〈0.01）. Compared to other groups and other time points, progenitor celt counts increased significantly after 2-hour EECP treatment （108±13 vs 26±6 per 10^5 leukocytes, P 〈0.01）, but not at week 18. The prog
基金This study was supported by grants from China Science and Technology Planning Foundation of Beijing Municipal Science ＆ Technology Commission （No. D0906006000091）, National Natural Science Foundation of China （No. 30770581）, the Foundation of President of Anzhen Hospital （No. 2010Z03） and a grant from Key Laboratory of Cardiovascular Remolding Associated Diseases.Acknowledgements： The authors sincerely thank other investigators, coordinators, physicians and nurses, who made invaluable contributions to this study. The authors are also grateful to TONG Zhi and LIU Shu for their editorial assistance.
文摘Background There are numerous articles on the endothelial progenitor cells （EPCs） in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome （ACS） are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients. Methods Patients were enrolled with admitted ACS （n=25） and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease （CAD） controls. EPCs were defined as CD34＋/CD133＋/VEGFR-2＋ and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit （CFU）, proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 （MMP-9） was detected in all patients as well. Results The two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects （15.6±2.7 vs. 6.0±0.8 /100 000 events, P 〈0.01）. CFU was not statistically different between the two groups （10.8±2.9 vs. 8.2±1.8, number/well, P 〉0.05）. Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation （0.498±0.035 vs. 0.895±0.067, OD value, P〈0.01） and migration capacity （20.5±3.4 vs. 30.7±4.3, number/well, P 〈0.01） compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group （（18.3±2.. 1 ）% vs. （7.8±0.4）%, P 〈0.01）. Conclusions Patients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects.
基金Supported by CNCSIS–UEFISCSU, No.1159, PNⅡ-IDEI code 1043/2008CNMP project number 42138, PNⅡ-Parteneriat code 3334/2008+1 种基金European Social Fund-‘Cristofor Ⅰ. Simionescu’ Postdoctoral Fellowship Programme (ID POSDRU/89/1.5/S/55216)Sectoral Operational Programme Human Resources Development 2007–2013, Romanian Academy
文摘The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.
基金This work was supported by grants from Zhejiang Provincial Natural Science Foundation of China （No.Y12H070014） and National Natural Science Foundation of China （No.30972592）.
文摘Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are involved in angiogenesis and maintenance of vascular integrity following HLI.On the other side,it has been proved that Astragalus polysaccharide （APS） could promote angiogenesis.In the present study,we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin （STZ）-induced diabetes.Methods Rats （n=110） were randomly assigned to the following groups：sham group,ischemia group,APS group,EPCs group and APS＋EPCs group.APS,EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction,and 6 rats were assessed by angiography at 28 days after induction of HLI,6 rats were sacrificed at the same time point to take histological studies,biochemical tests were also performed at that point in the rest rats.Results APS or EPCs treatment induced an increase,respectively,in the protein expression of vascular endothelial growth factor （VEGF） （36.61%,61.59%）,VEGF receptor-1 （VEGFR-1） （35.50%,57.33%）,VEGFR-2 （31.75%,41.89%）,Angiopoietin-1 （Ang-1） （37.57%,64.66%） and Tie-2 （42.55%,76.94%） （P 〈0.05）,after HLI injury.And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats,through elevating protein expression of VEGF （99.67%）,VEGFR-1 （105.33%）,VEGFR2 （72.05%）,Ang-1 （114.30%） and Tie-2 （111.87%） （P〈0.05）.Similarly,mRNA expression of VEGF,VEGFR-1,VEGFR2,Ang-1,Tie-2 also show similar trends as well as protein expression （P〈0.05）.Conclusion APS or EPCs could enhance angiogenesis,and the combined treatment leads to better effort,at least,partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.
基金the grants from Shanghai Science Committee Fund for Key Research Project(No.04JC14012)Fudan University Med-X Fund Abstract
文摘Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells （EPCs） and decellularized valve scaffolds. Methods Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 × 10^6 cells/cm^2 and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction （RT-PCR） analysis for the expression of endothelial nitric oxide synthase （eNOS） and tissue-type plasminogen activator （t-PA）.Results EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor （vWF） and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 （UEA-1）, and took up Dil-labeled low density lipoprotein （Dil-Ac-LDL）. After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolay
基金Supported by the National Natural Science Foundation of China,No.30772577 and No.81060015the Gansu Province Science Foundation for Young Scholars,No.145RJYA320
文摘AIM To investigate the significance of endothelial progenitor cells (EPCs) in predicting severe acute pancreatitis (SAP). METHODS We recruited 71 patients with acute pancreatitis (AP) and excluded 11 of them; finally, cases of mild acute pancreatitis (MAP) (n = 30) and SAP (n = 30), and healthy volunteers (n = 20) were internalized to investigate levels of EPCs, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), fibrinogen (FIB) and white blood cells (WBC) in peripheral blood. RESULTS The levels of TNF-alpha, WBC, FIB and CRP were higher both in SAP and MAP cases than in healthy volunteers (P < 0.05, all). Interestingly, the level of EPCs was higher in SAP than MAP (1.63% +/- 1.47% vs 6.61% +/- 4.28%, P < 0.01), but there was no significant difference between the MAP cases and healthy volunteers (1.63% +/- 1.47% vs 0.55% +/- 0.54%, P > 0.05). Receiver operating characteristics curve (ROC) showed that EPCs, TNF-alpha, CRP and FIB were significantly associated with SAP, especially EPCs and CRP were optimal predictive markers of SAP. When the cut-off point for EPCs and CRP were 2.26% and 5.94 mg/dL, the sensitivities were 90.0% and 73.3%, and the specificities were 83.3% and 96.7%. Although, CRP had the highest specificity, and EPCs had the highest sensitivity and highest area under the curve value (0.93). CONCLUSION Data suggest that EPCs may be a new biological marker in predicting SAP.
基金This study was supported by a grant from the National Natural Science Foundation of China(No.30570720)
文摘Objective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007. The search term was ＂endothelial progenitor cells＂. Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used. Results Progenitor cells in bone marrow, peripheral blood and adventitia can differentiate into mature endothelial cells （ECs）. The progenitor cells, which express certain surface markers including AC133, CD34 and KDR, enable restoration of the microcirculation and ECs when injury or ischaemia occurs. Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development. Moreover, their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors. Impairment of the progenitor cells might limit the regenerative capacity, even lead to the development of atherosclerosis or other vascular diseases. Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases. However, many challenges remain in understanding differentiation of endothelial progenitor cells, their mobilization and revascularization.
基金supported by the Science and Technology Commission of Shanghai Municipality, China (09jc1403500)
文摘Objective Sevoflurane is widely used in pediatric anesthesia and former studies showed that it causes neurodegeneration in the developing brain. The present study was carried out to investigate the effects of sevoflurane on neurogenesis, neurodegeneration and behavior. Methods We administered 5-bromodeoxyuridine, an S-phase marker, before, during, and after 4 h of sevoflurane given to rats on postnatal day 7 to assess dentate gyrus progenitor proliferation and Fluoro-Jade staining for degeneration. Spatial reference memory was tested 2 and 6 weeks after anesthesia. Results Sevoflurane decreased progenitor proliferation and increased cell death until at least 4 days after anesthesia. Spatial reference memory was not affected at 2 weeks but was affected at 6 weeks after sevoflurane administration. Conclusion Sevoflurane reduces neurogenesis and increases the death of progenitor cells in developing brain. This might mediate the lateonset neurocognitive outcome after sevoflurane application.
