scholarly journals Endothelial Progenitor Cells as a Marker of Vascular Damage But not a Predictor in Acute Microangiopathy-Associated Stroke

2020 ◽  
Vol 9 (7) ◽  
pp. 2248 ◽  
Author(s):  
Adam Wiśniewski ◽  
Joanna Boinska ◽  
Katarzyna Ziołkowska ◽  
Adam Lemanowicz ◽  
Karolina Filipska ◽  
...  
Keyword(s):  
Risk Factors ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Biochemical Parameters ◽  
Hemorrhagic Stroke ◽  
Stroke Onset ◽  
Control Group ◽  
Radiological Findings ◽  
Endothelial Progenitor ◽  
Phenotype Classification

Background: The aim of the study was to assess the number of endothelial progenitor cells (EPCs) in patients with acute stroke due to cerebral microangiopathy and evaluate whether there is a relationship between their number and clinical status, radiological findings, risk factors, selected biochemical parameters, and prognosis, both in ischemic and hemorrhagic stroke. Methods: In total, 66 patients with lacunar ischemic stroke, 38 patients with typical location hemorrhagic stroke, and 22 subjects from the control group without acute cerebrovascular incidents were included in the prospective observational study. The number of EPCs was determined in serum on the first and eighth day after stroke onset using flow cytometry and identified with the immune-phenotype classification determinant (CD)45−, CD34+, CD133+. Results: We demonstrated a significantly higher number of EPCs on the first day of stroke compared to the control group (med. 17.75 cells/µL (0–488 cells/µL) vs. 5.24 cells/µL (0–95 cells/µL); p = 0.0006). We did not find a relationship between the number of EPCs in the acute phase of stroke and the biochemical parameters, vascular risk factors, or clinical condition. In females, the higher number of EPCs on the first day of stroke is related to a favorable functional outcome on the eighth day after the stroke onset compared to males (p = 0.0355). We found that a higher volume of the hemorrhagic focus on the first day was correlated with a lower number of EPCs on the first day (correlation coefficient (R) = −0.3378, p = 0.0471), and a higher number of EPCs on the first day of the hemorrhagic stroke was correlated with a lower degree of regression of the hemorrhagic focus (R = −0.3896, p = 0.0367). Conclusion: The study showed that endothelial progenitor cells are an early marker in acute microangiopathy-associated stroke regardless of etiology and may affect the radiological findings in hemorrhagic stroke. Nevertheless, their prognostic value remains doubtful in stroke patients.

Gene transfer of endothelial NO-synthase restores migratory capacity of endothelial progenitor cells from patients with coronary artery diseases

2007 ◽  
Vol 30 (4) ◽  
pp. 96
Author(s):  
Michael R. Ward ◽  
Qiuwang Zhang ◽  
Duncan J. Stewart ◽  
Michael J.B. Kutryk
Keyword(s):  
Risk Factors ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Fold Increase ◽  
No Synthase ◽  
Endothelial Progenitor ◽  
Migratory Capacity ◽  
Acute Mi ◽  
Cad Risk

Autologous endothelial progenitor cells (EPCs) have been used extensively in the development of cell-based therapy for acute MI. However, EPCs isolated from patients with CAD and/or CAD risk factors have reduced regenerative activity compared to cells from healthy subjects. As in endothelial cells, endothelial NO synthase (eNOS) expression and subsequent NO production are believed to be critical determinants of EPC function. Recently, the ability of EPCs to migrate in vitro in response to chemotactic stimuli has been shown to predict their regenerative capacity in clinical studies. Therefore, we hypothesized that the regenerative function of EPCs from patients with or at high risk for CAD will be enhanced by overexpression of eNOS, as assessed by migratory capacity. Methods: EPCs were isolated from the blood of human subjects with CAD risk factors (>15% Framingham risk score; FRS) (± CAD) by Ficoll gradient separation and differential culture. Following 3 days in culture, cells were transduced using lentivirus vectors containing either eNOS or GFP (sham) at an MOI of 3. The cells were cultured for an additional 5 days before being used in functional assays. Cell migration and chemotaxis in response to VEGF (50 ng/mL) and SDF-1 (100 ng/mL) were assessed using a modified Boyden Chamber assay. Results: Transduction at an MOI of 3 led to a ~90-100-fold increase in eNOS mRNA expression and a 5-6 fold increase in eNOS protein expression, as assessed by qRT-PCR and Western Blotting. Moreover, there was a significant improvement in the migration of EPCs following eNOS transduction compared to sham-transduced EPCs in response to both VEGF (44.3 ± 8.4 vs. 31.1 ± 4.6 cells/high power field; n=10, p < 0.05) and SDF-1 (51.9 ± 11.1 vs. 34.5 ± 3.3 cells/HPF; n=10, p < 0.05). Conclusions: These data show that the reduced migration capacity of EPCs isolated from patients with CAD and/or CAD risk factors can be significantly improved through eNOS overexpression in these cells. Thus, eNOS transduction of autologous EPCs may enhance their ability to restore myocardial perfusion and function following acute MI. We intend to further explore the regenerative potential of eNOS-transduced EPCs using various in vitro and in vivo models.

Elevated Inflammatory Parameter Levels Negatively Impact Populations of Circulating Stem Cells (CD133+), Early Endothelial Progenitor Cells (CD133+/VEGFR2+), and Fibroblast Growth Factor in Stroke Patients

2019 ◽  
Vol 16 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Monika Golab-Janowska ◽  
Edyta Paczkowska ◽  
Boguslaw Machalinski ◽  
Dariusz Kotlega ◽  
Agnieszka Meller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cells ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Plasma Levels ◽  
Fibroblast Growth ◽  
Vascular Risk ◽  
Endothelial Progenitor ◽  
Inflammatory Parameters

Background: Endothelial Progenitor Cells (EPCs) are important players in neovascularization, mobilized through signalling by Angiogenic Growth Factors (AGFs) such as Vascular Endothelial Growth Factor (VEGF) and fibroblast growth factor (FGF). In vitro, inflammatory parameters impair the function and influence of EPCs on AGFs. However, this connection is not clear in vivo. To understand the mechanisms of augmented arteriogenesis and angiogenesis in acute ischemic stroke (AIS) patients, we investigated whether circulating stem cells (CD133+), early endothelial progenitor cells (CD133+/VEGFR2+), and endothelial cells (ECs; CD34¯/CD133¯/VEGFR2+) were increasingly mobilized during AIS, and whether there were correlations between EPC levels, growth factor levels and inflammatory parameters. Methods: Data on demographics, classical vascular risk factors, neurological deficit information (assessed using the National Institutes of Health Stroke Scale), and treatment were collected from 43 consecutive AIS patients (group I). Risk factor control patients (group II) included 22 nonstroke subjects matched by age, gender, and traditional vascular risk factors. EPCs were measured by flow cytometry and the populations of circulating stem cells (CD133+), early EPCs (CD133+/VEGFR2+), and ECs (CD34¯/CD133¯/VEGFR2+) were analysed. Correlations between EPC levels and VEGF and FGF vascular growth factor levels as well as the influence of inflammatory parameters on EPCs and AGFs were assessed. Results: Patient ages ranged from 54 to 92 years (mean age 75.2 ± 11.3 years). The number of circulating CD34¯/CD133¯/VEGF-R2+ cells was significantly higher in AIS patients than in control patients (p < 0.05). VEGF plasma levels were also significantly higher in AIS patients compared to control patients on day 7 (p < 0.05). FGF plasma levels in patients with AIS were significantly higher than those in the control group on day 3 (p < 0.05). There were no correlations between increased VEGF and FGF levels and the number of CD133+, CD133+/VEGFR2+, or CD34¯/CD133¯/VEGFR2+ cells. Leukocyte levels, FGF plasma levels, and the number of early EPCs were negatively correlated on day 3. High sensitivity C-reactive protein levels and the number of CD133+ and CD133+/VEGFR2+ cells were negatively correlated on day 7. In addition, there was a negative correlation between fibrinogen levels and FGF plasma levels as well as the number of early EPCs (CD133+/VEGFR2+). Conclusion: AIS patients exhibited increased numbers of early EPCs (CD133+/VEGFR2+) and AGF (VEGF and FGF) levels. A negative correlation between inflammatory parameters and AGFs and EPCs indicated the unfavourable influence of inflammatory factors on EPC differentiation and survival. Moreover, these correlations represented an important mechanism linking inflammation to vascular disease.

scholarly journals Does erythropoietin therapy affect circulating endothelial cells in hemodialysis patients?

2020 ◽  
pp. 29-37
Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor Cell ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Hemodialysis Patients ◽  
Circulating Endothelial Cells ◽  
Control Group ◽  
Endothelial Progenitor

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.

Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke — evaluating the impact of therapeutic time points on prognostic outcomes

2020 ◽  
Author(s):  
Kun-Chen Lin ◽  
Han-Tan Chai ◽  
Kuan-Hung Chen ◽  
Pei‐Hsun Sung ◽  
John Y. Chiang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Optimal Time ◽  
Control Group ◽  
Endothelial Progenitor ◽  
Group 2 ◽  
The Impact ◽  
Carotid Arterial ◽  
Group 1

Abstract Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x106 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.

scholarly journals Protective Effect of Silymarin against Rapamycin-induced Apoptosis and Proliferation Inhibition in Endothelial Progenitor Cells

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Concentration Dependent Manner ◽  
Inhibition Of Proliferation ◽  
And Migration ◽  
Proliferation And Migration

For this study, peripheral blood samples were collected from human volunteers. Mononuclear cells (MNC) were separated by density centrifugation and were induced to differentiate into endothelial progenitor cells (EPCs) in vitro. Different concentrations of rapamycin and silymarin were introduced to the EPCs over 24 hours and then EPCs were analyzed for proliferation, migration, apoptosis and angiogenesis. Compared with the control group, rapamycin (1, 10, 100 ng/mL) inhibited the proliferation and migration of EPCs in a concentration dependent manner ( P<0.05). Silymarin (50, 100 μg/mL) enhanced the proliferation and migration of EPCs and inhibited apoptosis in a concentration dependent manner ( P<0.05). By adding rapamycin (1 ng/mL) and silymarin (25, 50, 100 μg/mL) over 24 hours, silymarin inhibited the pro-apoptotic effect of rapamycin on EPCs, and reversed the inhibition of proliferation, migration and angiogenesis of EPCs by rapamycin ( P<0.05).

Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease

2010 ◽  
Vol 120 (7) ◽  
pp. 263-283 ◽  
Author(s):  
Shaundeep Sen ◽  
Stephen P. McDonald ◽  
P. Toby H. Coates ◽  
Claudine S. Bonder
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Ex Vivo ◽  
Individual Risk ◽  
Vascular Risk ◽  
Vascular Control ◽  
Endothelial Progenitor

Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.

scholarly journals Ratio of EPC and CEC as Endotel Dysfunction Predictor in High Risk Group with Farmingham Risk Score 10 Years Category

2013 ◽  
pp. 14-9
Author(s):  
Wiwit Nurwidyaningtyas ◽  
Djanggan Sargowo ◽  
Achdiat Agoes ◽  
Titin Andri W ◽  
S Satuman
Keyword(s):  
High Risk ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Risk Score ◽  
Risk Group ◽  
High Risk Group ◽  
Control Group ◽  
Endothelial Progenitor ◽  
Group I ◽  
Endothelial Stress

Research background. Circulating Endothelial Cells (CEC) is a reflection of endothelial damage or endothelial stress, increasing of CEC amount depend on endothelial mechanism, edothelial adhesivity damage and cellular apoptosis as a result of decreasing sitoskleleton function. If higher exposure affects the increasing of CEC amount,VEGF other growth factor mediators will be reflected as endothelial stress manifestation which roles in the increasing of re-population and Endothelial Progenitor Cells (EPC) differentiation. Endothelial Progenitor Cells is a mononuclear cell (a part of stem cell) that could change to be mature endothel and roles in re-edothelialisation and neovascularisation. This research aimed to investigate the ratio of EPC : CEC in risk group through Framingham Risk Score (FRS) 10 years approach as endothelial dysfunction predictor.Research method and result. There were 55 research subjects whom taken by FRS scoring and devided into some risk groups and two control groups. They were control group I (health) and control group II (sick). Base blood was taken to every each of them to analyze their EPC and CEC with Flowcytometry. EPC was analyzed by CD34 Per CP Santa Cruz SC-19621 and CD 133 FITC (fluorescein isothiocyanate) Bioss bs-0395R-FITCmarker.WhileCEC was analyzed CD45 FITC Biolegend 202205 dan CD 146 PE Biolegend 134704 marker. Result showed, there was significant ratio differences of EPC : CEC in those six groups which was proven by p-value 0.032< ? (0.05). The higher ratio was in high risk group (139.06).Conclusion. Research showed that EPC amount was increase related to the increasing of high risk level according to FRS 10 years, but its increasing did not followed by its ability to homing in injury area as role part in re-endothelialisation process. It found that EPC amount was higher in high risk group than in low risk group.

Sign in / Sign up

Export Citation Format

Share Document