scholarly journals Multilayer Membranes of Glycosaminoglycans and Collagen I Biomaterials Modulate the Function and Microvesicle Release of Endothelial Progenitor Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Bingyan Dai ◽  
Qunwen Pan ◽  
Zhanghua Li ◽  
Mingyan Zhao ◽  
Xiaorong Liao ◽  
...  

Multilayer composite membrane of biomaterials can increase the function of adipose stem cells or osteoprogenitor cells. Recent evidence indicates endothelial progenitor cells (EPCs) and EPCs released microvesicles (MVs) play important roles in angiogenesis and vascular repair. Here, we investigated the effects of biomaterial multilayer membranes of hyaluronic acid (HA) or chondroitin sulfate (CS) and Collagen I (Col I) on the functions and MVs release of EPCs. Layer-by-layer (LBL) technology was applied to construct the multilayer composite membranes. Four types of the membranes constructed by adsorbing either HA or CS and Col I alternatively with different top layers were studied. The results showed that all four types of multilayer composite membranes could promote EPCs proliferation and migration and inhibit cell senility, apoptosis, and the expression of activated caspase-3. Interestingly, these biomaterials increased the release and the miR-126 level of EPCs-MVs. Moreover, the CS-Col I membrane with CS on the top layer showed the most effects on promoting EPCs proliferation, EPCs-MV release, and miR-126 level in EPCs-MVs. In conclusion, HA/CS and Collagen I composed multilayer composite membranes can promote EPCs functions and release of miR-126 riched EPCs-MVs, which provides a novel strategy for tissue repair treatment.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi-Nan Lee ◽  
Yih-Jer Wu ◽  
Hsin-I. Lee ◽  
Hsueh-Hsiao Wang ◽  
Chiung-Yin Chang ◽  
...  

AbstractThe therapeutic effects of ultrasonic microbubble transfection (UMT)-based vascular endothelial growth factor 165 (VEGF165) gene delivery on young and senescent endothelial progenitor cells (EPCs) were investigated. By UMT, plasmid DNA (pDNA) can be delivered into both young EPCs and senescent EPCs. In the UMT groups, higher pDNA-derived protein expression was found in senescent EPCs than in young EPCs. Consistent with this finding, a higher intracellular level of pDNA copy number was detected in senescent EPCs, with a peak at the 2-h time point post UMT. Ultrasonic microbubble delivery with or without VEGF improved the angiogenic properties, including the proliferation and/or migration activities, of senescent EPCs. Supernatants from young and senescent EPCs subjected to UMT-mediated VEGF transfection enhanced the proliferation and migration of human aortic endothelial cells (HAECs), and the supernatant of senescent EPCs enhanced proliferation more strongly than the supernatant from young EPCs. In the UMT groups, the stronger enhancing effect of the supernatant from senescent cells on HAEC proliferation was consistent with the higher intracellular VEGF pDNA copy number and level of protein production per cell in the supernatant from senescent cells in comparison to the supernatant from young EPCs. Given that limitations for cell therapies are the inadequate number of transplanted cells and/or insufficient cell angiogenesis, these findings provide a foundation for enhancing the therapeutic angiogenic effect of cell therapy with senescent EPCs in ischaemic cardiovascular diseases.


2021 ◽  
pp. 199-204
Author(s):  
N. A. Kuzubova ◽  
O. N. Titova ◽  
E. S. Lebedeva ◽  
E. V. Volchkova

Pulmonary vascular endothelium dysfunction is one of the main pathogenic factors responsible for many clinical manifestations of the severe course of COVID-19. Circulating endothelial progenitor cells (EPCs) are the endogenous regenerative reserve that maintains the integrity of the vascular endothelium and its restoration in case of damage by pathogenic factors. A decrease in the circulating EPCs is regarded as a predictor of morbidity and mortality in conditions associated with development of endothelial dysfunction, including COVID-19. The exact phenotype of progenitor cells capable of differentiating into endothelial cells has not been determined. In most laboratories antigens CD133+, CD34+, VEGFR-2+ (CD 309) or combination of these are used to identify EPCs. The process of EPCs mobilization and migration is controlled by molecular signals from immune cells located in the damage area. Stromal cell factor 1 (SDF-1), produced by the bone marrow and many other tissues, is an important chemoattractant for EPCs which express its receptors. The results of studies carried out in 2020 indicate that SARS-Cov-2 infects both hematopoietic stem cells, transforming into EPCs, and directly circulating EPCs, causing inflammatory and procoagulant reactions that complicate the COVID-19 course. There is no consensus on the mechanism of EPCs infection with coronavirus – directly through the expression of angiotensin-converting enzyme (ACE2) receptor or through an ACE2-independent mechanism. Today there is no effective therapy for COVID-19. The use of the EPCs regenerative potential, and the search for ways to enhance the EPCs mobilization from the depot, and increase their functional activity may become a promising approach to the prevention of severe complications and mortality from COVID-19.


2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  

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).


2021 ◽  
Vol 18 (10) ◽  
pp. 2117-2123
Author(s):  
Youcai Yuan ◽  
Xiaoke Zhang ◽  
Huan Zhang ◽  
Bifeng Gao

Purpose: To investigate the effect of Xiaoke Tongbi granule (XTG) on the proliferation, migration and tubule-forming ability of endothelial progenitor cells (EPCs) of rats under high glucose conditions. Methods: Six specific pathogen-free (SPF) and twenty-four healthy rats (mean weight = 200 ± 20 g) were used in this study. Twenty-four (24) healthy rats were treated with graded concentrations of XTG (0.75 – 2.25 g/mL) for 7 days, and were thereafter euthanized to obtain serum which was later used to treat EPCs isolated from bone marrow of SPF rats. The EPCs were seeded in culture plates pre-coated with human fibronectin, and cultured at 37 °C for 72 h in a humidified atmosphere of 5 % CO2 and 95 % air. Cell viability and apoptosis were assessed using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The morphology of isolated EPCs was assessed by immunofluorescence. Results: The isolated EPCs exhibited normal morphology, and were CD34-positive. Proliferation and migration of EPCs, and number of tubular structures formed were significantly suppressed under high glucose conditions, but were significantly and concentration-dependently promoted by XTG treatment (p < 0.05). Treatment with XTG also significantly improved the morphology of isolated EPCs (p < 0.05). Apoptosis was significantly promoted by high glucose conditions, but was significantly and concentration-dependently reduced by XTG treatment (p < 0.05). The incidence of tubule formation in high glucose group was 0.63 %, but was progressively increased from 1.37 to 1.52 % after treatment with graded concentrations of XTG. Conclusion: These results indicate that XTG reverses the effect of high glucose environment on EPC proliferation, migration and tubule-forming ability.


2019 ◽  
Vol 87 (3) ◽  
pp. 16
Author(s):  
Yudi Her Oktaviono ◽  
Makhyan Jibril Al-Farabi ◽  
Luh Oliva Saraswati Suastika ◽  
Febriyanti Hartono ◽  
Yanni Dirgantara ◽  
...  

Impairment of the endothelial progenitor cells (EPCs) ability to proliferate and migrate in the patients with coronary heart disease (CHD) is partly caused by oxidative stress. This research evaluates the effect of treatment with Ipomoea batatas L./purple sweet potato (PSP) extract and l-ascorbic acid on the proliferation and migration of impaired EPCs. EPCs were isolated from CHD patient’s peripheral blood. EPCs culture were cultivated and divided into control (untreated), PSP extract treatment (dose 1 and 25 μg/mL), and l-ascorbic acid treatment (dose 10 and 250 μg/mL) groups for 48 h. EPCs proliferation was analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay, and migration was evaluated with the cell migration assay kit. Statistical tests were evaluated using SPSS 25.0. This research showed that EPCs proliferation and migration was significantly higher in all PSP extract and l-ascorbic acid treatment compared to the control (p < 0.001). EPCs migration on treatment with a PSP extract dose of 25 μg/mL was significantly higher compared to the treatment with l-ascorbic acid dose of 250 μg/mL (303,000 ± 1000 compared to 215,000 ± 3000 cells, p< 0.001). In conclusion, both treatments with PSP extract and l-ascorbic acid can improve the proliferation and migration of impaired EPCs. At the dose of 25 μg/mL, PSP extract seems to be superior to the l-ascorbic acid dose of 250 μg/mL to improve EPCs migration.


2019 ◽  
Vol 317 (5) ◽  
pp. C932-C941 ◽  
Author(s):  
Ming Yi ◽  
Ye Wu ◽  
Jun Long ◽  
Fei Liu ◽  
Zhi Liu ◽  
...  

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs have been found to be increased in cardiovascular disease patients and are considered to be involved in the process of coronary atherosclerosis. Since OCN has been proven to prevent endothelial dysfunction, this study aimed to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor G protein-coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay, and the migration of endothelial cells was detected by wound healing assay. A tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here, we presented that OCN was packed into Exos and was able to be transferred to the RAOECs via exosome incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efficiency in promoting RAOEC proliferation and migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPCs have a beneficial regulating effect on endothelial cells, which involved enhanced OCN-GPRC6A signaling.


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