The prostacyclin analogue iloprost increases circulating endothelial progenitor cells in patients with critical limb ischemia

2008 ◽  
Vol 100 (05) ◽  
pp. 871-877 ◽  
Author(s):  
Rossella Di Stefano ◽  
Maria Barsotti ◽  
Elio Melillo ◽  
Mariacarla Iorio ◽  
Tatiana Santoni ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Density Lipoprotein ◽  
Limb Ischemia ◽  
Disease Stage ◽  
Endothelial Progenitor

SummaryPatients with critical limb ischemia (CLI) have low levels of endothelial progenitor cells (EPC). Iloprost has been demonstrated to stimulate vascular endothelial growth factor (VEGF) and promote angiogenesis. We investigated the effects of iloprost on EPC levels in vivo in CLI patients. Twenty-three patients with stage III and IV CLI were treated with iloprost for four weeks, improving clinical and instrumental parameters. Mononuclear cells isolated from peripheral blood were cultured to obtain “early” EPC, evaluated counting adherent cells with double positivity for acetylated low-density lipoprotein uptake and Ulex Europaeus lectin at flow cytometry. These cells also co-expressed the monocyte markers CD14 and CD45.Iloprost increased EPC number in the whole patient population: pre-treatment median: 13,812/ml; range: 1,263–83,648/ml; post-treatment median: 23,739/ml; range: 3,385–99,251/ml; p=0.035, irrespective of age, sex, disease stage or atherosclerosis risk factors. In conclusion, iloprost increases EPC number in peripheral blood in vivo. Such an effect may have therapeutic relevance.

Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia

Angiogenesis ◽  
2015 ◽  
Vol 19 (1) ◽  
pp. 67-78 ◽  
Author(s):  
Jörn F. Dopheide ◽  
Philipp Geissler ◽  
Jennifer Rubrech ◽  
Amelie Trumpp ◽  
Geraldine C. Zeller ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Endothelial Progenitor

Peripheral endothelial progenitor cells (CD133+) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up

Cytotherapy ◽  
2007 ◽  
Vol 9 (1) ◽  
pp. 99-102 ◽  
Author(s):  
M.C. Cañizo ◽  
F. Lozano ◽  
J.R. González-Porras ◽  
M. Barros ◽  
N. López-Holgado ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Endothelial Progenitor ◽  
One Year

Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia

Cytotherapy ◽  
2012 ◽  
Vol 14 (2) ◽  
pp. 232-239 ◽  
Author(s):  
David M. Smadja ◽  
Jean-Paul Duong-van-Huyen ◽  
Liliane Dal Cortivo ◽  
Anne Blanchard ◽  
Patrick Bruneval ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Endothelial Progenitor ◽  
Therapy Success

miR-126 modulates angiogenic growth parameters of peripheral blood endothelial progenitor cells

2015 ◽  
Vol 396 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Sebastian M. Goerke ◽  
Lena S. Kiefer ◽  
G. Björn Stark ◽  
Filip Simunovic ◽  
Günter Finkenzeller
Keyword(s):  
Tissue Engineering ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Growth Parameters ◽  
Therapeutic Option ◽  
Tube Formation ◽  
Loss Of Function ◽  
Endothelial Progenitor

Abstract Vascularization plays an important role in tissue engineering applications. It is known that implantation of differentiated endothelial cells or endothelial progenitor cells (EPCs) from cord blood (cbEPCs) gives rise to the formation of a complex functional neovasculature, whereas EPCs isolated from peripheral blood (pbEPCs) have a limited capability to form blood vessels upon implantation. MicroRNA-126 (miR-126) has been shown to have pro-angiogenic effects in vivo. In this study, we investigated whether modulation of miR-126 expression in pbEPCs may alter their angiogenic properties. Gain of function and loss of function experiments revealed that miR-126 has anti-angiogenic effects in pbEPCs. Overexpression of miR-126 resulted in decreased proliferation, migration, invasion and tube formation, while inhibition of miR-126 induced the opposite effects. However, modulation of miR-126 expression did not influence apoptotic susceptibility of pbEPCs. This study provides evidence that inhibition of miR-126 improves angiogenesis-related growth parameters in pbEPCs and may represent a therapeutic option to ameliorate the angiogenic and vasculogenic properties of pbEPCs.

scholarly journals Role of β2-integrins for homing and neovascularization capacity of endothelial progenitor cells

2004 ◽  
Vol 201 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Emmanouil Chavakis ◽  
Alexandra Aicher ◽  
Christopher Heeschen ◽  
Ken-ichiro Sasaki ◽  
Ralf Kaiser ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ex Vivo ◽  
Limb Ischemia ◽  
Endothelial Progenitor ◽  
Cell Monolayers ◽  
Β2 Integrins

The mechanisms of homing of endothelial progenitor cells (EPCs) to sites of ischemia are unclear. Here, we demonstrate that ex vivo–expanded EPCs as well as murine hematopoietic Sca-1+/Lin− progenitor cells express β2-integrins, which mediate the adhesion of EPCs to endothelial cell monolayers and their chemokine-induced transendothelial migration in vitro. In a murine model of hind limb ischemia, Sca-1+/Lin− hematopoietic progenitor cells from β2-integrin–deficient mice are less capable of homing to sites of ischemia and of improving neovascularization. Preactivation of the β2-integrins expressed on EPCs by activating antibodies augments the EPC-induced neovascularization in vivo. These results provide evidence for a novel function of β2-integrins in postnatal vasculogenesis.

scholarly journals EFFECT OF FLAVONOIDS ON OXIDATIVE STRESS, APOPTOSIS, AND CELL MARKERS OF PERIPHERAL BLOOD-DERIVED ENDOTHELIAL PROGENITOR CELLS: AN IN VITRO STUDY

2021 ◽  
pp. 39-42
Author(s):  
WAHYU WIDOWATI ◽  
RIMONTA F. GUNANEGARA ◽  
TERESA LILIANA WARGASETIA ◽  
HANNA SARI WIDYA KUSUMA ◽  
SEILA ARUMWARDANA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
In Vitro Study ◽  
Endothelial Progenitor ◽  
Peripheral Blood Mononuclear ◽  
Cell Markers

Objective: Circulating EPCs (endothelial progenitor cells) play a role in neovascularization and vascular repair. Oxidative stress impairs endothelial progenitor. Flavonoid is a phytochemical compound for antioxidant activity. Flavonoid effects toward oxidative stress, apoptosis, and expression of the cell markers on EPCs are not fully understood. This study was aimed to elucidate the effects of quercetin, kaempferol, and myricetin toward oxidative stress, apoptosis, and cell markers of peripheral blood-derived-EPCs. Methods: EPCs (endothelial progenitor cells) were isolated from peripheral blood mononuclear cells (PBMNCs) using cultivation under EPCs spesific media. Oxidative stress in EPCs was induced by H2O2 and then treated by quercetin, kaempferol, and myricetin. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, while intracellular reactive oxygen species (ROS), apoptosis and characterization of cells, which expressed CD133 and KDR, was measured using flow cytometry. Results: Quercetin, kaempferol, and myricetin at concentration 12.50 µmol/l were not toxic on EPCs as the cells viability were 96.11±4.03%, 95.42±7.75%, and 94.22±9.49%, respectively. Flavonoids decreased intracellular ROS level in EPCs (quercetin: 14.38±1.47%, kaempferol: 20.21±6.25%, and myricetin: 13.88±4.02%) compared to EPCs treated with H2O2 (30.70%±1.04). Percetage of EPCs apoptosis was not significantly different among each treatment. Immunophenotyping showed the increasing of CD133 and KDR expression in EPCs treated with flavonoids. Conclusion: Quercetin, kaempferol, and myricetin were safe for EPCs, decreased ROS levels, and increased CD133 and KDR expression. However, the flavonoids did not significantly affect EPCs apoptosis.

scholarly journals Human peripheral blood mononuclear cells enriched in endothelial progenitor cells via quality and quantity controlled culture accelerate vascularization and wound healing in a porcine wound model

2018 ◽  
Vol 27 (7) ◽  
pp. 1068-1079 ◽  
Author(s):  
Makiko Kado ◽  
Rica Tanaka ◽  
Kayo Arita ◽  
Kayoko Okada ◽  
Rie Ito-Hirano ◽  
...  
Keyword(s):  
Wound Healing ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Skin Defect ◽  
Endothelial Progenitor ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

The transplantation of endothelial progenitor cells (EPCs) is used to promote wound angiogenesis. In patients with chronic wounds and accompanying morbidities, EPCs are often compromised in number and function. To overcome these limitations, we previously developed a quality and quantity controlled (QQ) culture system to enrich peripheral blood mononuclear cells (PBMNCs) in EPCs. To evaluate the wound healing efficacy of mononuclear cells (MNCs) harvested after QQ culture (QQMNCs), preclinical studies were performed on large animals. MNCs harvested from the blood of healthy human subjects were cultured in the presence of angiogenic cytokines and growth factors in a serum-free medium for 7 days. A total of 5 × 106 QQMNCs per full-thickness skin defect or control saline was injected into wounds induced in cyclosporine-immunosuppressed pigs. EPC colony-forming assays revealed a significantly higher number of definitive (partially differentiated) EPC colony-forming units in QQMNCs. Flow cytometry evaluation of QQMNC surface markers showed enrichment of CD34+ and CD133+ stem cell populations, significant reduction in CCR2+ cell percentages, and a greater than 10-fold increase in the percentage of anti-inflammatory M2-type macrophages (CD206+ cells) compared with PBMNCs. Wounds treated with QQMNCs had a significantly higher closure rate. Wounds were harvested, frozen, and sectioned at day 21 postoperatively. Hematoxylin and eosin staining revealed that the epithelization of QQMNC-treated wounds was more advanced than in controls. Treated wounds developed granulation tissue with more mature collagen and larger capillary networks. CD31 and human mitochondrial co-staining confirmed the presence of differentiated human cells within newly formed vessels. Real-time polymerase chain reaction (PCR) showed upregulation of interleukin 6 (IL-6), IL-10, and IL-4 in the wound bed, suggesting paracrine activity of the transplanted QQMNCs. Our data demonstrate for the first time that QQ culture of MNCs obtained from a small amount of peripheral blood yields vasculogenic and therapeutic cells effective in wound healing.

Abstract 019: Diabetic Endothelial Progenitor Cells in Combination with an RGDS Presenting Peptide Amphiphile Enhance Recovery from Critical Limb Ischemia in Diabetic Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Erin E Vaughan ◽  
Eduard Sleep ◽  
Sol Misener ◽  
Aiko Ito Klinger ◽  
Veronica Ramirez ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Laser Doppler ◽  
Diabetic Mice ◽  
Endothelial Progenitor ◽  
Peptide Amphiphile ◽  
Post Surgery ◽  
The Impact

Approximately two million people suffer from critical limb ischemia (CLI) with the prevalence of the disease expected to rise. Thus, there is a crucial need to develop new therapies to enhance angiogenesis and minimize the impact of the blocked vessel(s). Cell therapy using endothelial progenitor cells (EPCs) has shown some promise, however, the cells may not remain at the site of injury long enough to significantly impact the course of the disease. Further, the use of autologous cells may be problematic as the underlying disease, such as diabetes, which resulted in CLI also appears to negatively impact the function of EPCs. Thus, we propose to use a biomaterial in combination with the EPCs to enhance both the retention of cells at the site of injury and also enhance the function of the cells. A self-assembling peptide amphiphile (PA) was developed with an attached functional group consisting of the cell-attachment sequence of peptides identified in fibronectin: RGDS. We hypothesize that EPCs combined with RGDS PA will improve the angiogenic response in CLI. Indeed, in vitro we found that EPCs from diabetic mice (db/db) exhibited increased survival on an RGDS PA in comparison to a scrambled sequence (DGRS) PA as measured by calcein-AM and ethidium homodimer-1 staining. To test if this enhanced survival would improve critical limb ischemia in diabetic mice, uni-lateral ischemia was induced by ligation of the femoral artery. Three days post surgery ischemia was confirmed by laser Doppler and the following treatments were injected into the ischemic limb of the diabetic mice: (1) PBS (2) scrambled PA (3) RGDS (4) scrambled PA +100,000 diabetic EPCs (5) RGDS PA + 100,000 diabetic EPCs. At four weeks post-injection, blood flow (as measured by laser Doppler) was increased in the group receiving RGDS PA when compared to the other groups (n>6). Further, necrosis was decreased in the RGDS PA group and muscle regeneration, as measured by the number of central nuclei, was increased in the RGDS PA group. Taken together, these results suggest that RGDS PA in combination with db/db EPCs enhances recovery from CLI in diabetic mice.

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