Vasculogenesis and Its Cellular Therapeutic Applications

2016 ◽  
Vol 203 (3) ◽  
pp. 141-152 ◽  
Author(s):  
Anna Ratajska ◽  
Ewa Jankowska-Steifer ◽  
Elżbieta Czarnowska ◽  
Radosław Olkowski ◽  
Grzegorz Gula ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
De Novo ◽  
Current Knowledge ◽  
Endothelial Progenitor ◽  
Therapeutic Applications ◽  
Adult Tissues ◽  
Embryonic Life

Vasculogenesis was originally defined by Risau in 1997 [Nature 386: 671-674] as the de novo formation of vessels from endothelial progenitor cells (EPCs), so-called angioblasts. Initially, this process was believed to be related only to embryonic life; however, further studies reported vasculogenesis to occur also in adult tissues. This overview presents the current knowledge about the origin, differentiation and significance of EPCs that have been observed in various diseases, tumors, and reparative processes. We also summarize the knowledge of how to activate these cells for therapeutic purposes and the outcomes of the therapies.

Endothelial progenitor cells and hypertension: current concepts and future implications

2016 ◽  
Vol 130 (22) ◽  
pp. 2029-2042 ◽  
Author(s):  
Shengyuan Luo ◽  
Wenhao Xia ◽  
Cong Chen ◽  
Eric A. Robinson ◽  
Jun Tao
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Current Knowledge ◽  
Circulatory System ◽  
Essential Element ◽  
Future Research ◽  
Chronic Hypertension ◽  
Vascular Endothelial ◽  
Endothelial Progenitor ◽  
Endothelial Integrity

The discovery of endothelial progenitor cells (EPCs), a group of cells that play important roles in angiogenesis and the maintenance of vascular endothelial integrity, has led to considerable improvements in our understanding of the circulatory system and the regulatory mechanisms of vascular homoeostasis. Despite lingering disputes over where EPCs actually originate and how they facilitate angiogenesis, extensive research in the past decade has brought about significant advancements in this field of research, establishing EPCs as an essential element in the pathogenesis of various diseases. EPC and hypertensive disorders, especially essential hypertension (EH, also known as primary hypertension), represent one of the most appealing branches in this area of research. Chronic hypertension remains a major threat to public health, and the exact pathologic mechanisms of EH have never been fully elucidated. Is there a relationship between EPC and hypertension? If so, what is the nature of such relationship–is it mediated by blood pressure alterations, or other factors that lie in between? How can our current knowledge about EPCs be utilized to advance the prevention and clinical management of hypertension? In this review, we set out to answer these questions by summarizing the current concepts about EPC pathophysiology in the context of hypertension, while attempting to point out directions for future research on this subject.

Abstract 5998: Final Results of the HEALING 2B Trial to Evaluate a Bioengineered CD34 Antibody Coated Stent (Genous ™ Stent) Designed to Promote Vascular Healing by Capture of Circulating Endothelial Progenitor Cells in CAD Patients

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
H Duckers ◽  
Yoshinobu Onuma ◽  
Edouard Benit ◽  
Robert J de Winter ◽  
William Wijns ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Statin Therapy ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stent Thrombosis ◽  
De Novo ◽  
Endothelial Progenitor ◽  
Circulating Endothelial Progenitor Cells ◽  
Late Luminal Loss

Background: In contrast to a cytotoxic or cytostatic pharmacotherapy, promoting the vascular healing response by capturing and sequestering circulating endothelial progenitor cells (EPC) to the stent surface by a CD34 antibody coating (Genous ™ stent) may accelerate stent reendo-thelialization and prevent restenosis formation, as well as stent thrombosis (ST) Methods: The HEALING IIB study was a multi-center, prospective trial designed to assess the safety and efficacy of the Genous ™ bio-engineered stent in conjunction with HmG CoA reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions (n=100 pts). The primary safety endpoint was major adverse cardiac events (MACE) at 30 days, whereas the primary efficacy endpoint was late luminal loss by QCA at 6 months follow-up. Results: At interim analysis of the first 45 patients that completed the 6-month angiographic follow-up, the composite MACE rate was 11.1%, whereas 6.6% clinically justified target lesion revascularizations were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified stent thrombosis. Low circulating EPC titers were previously associated with a poor response to the EPC capture stent with TLR events and high late loss. Therefore, patients were pre-treated with Atorvastatin 80 mg qd prior to the PCI in order to augment EPC levels. Statin therapy stimulated the levels of committed EPCs by +294%, but failed to increase the titer of CD34+cells (+25%). Although statin pretreatment stimulated EPC levels, the angiographic outcome of the EPC capture stent was not improved in these patients: in-stent late luminal loss was 0.77±0.46 mm. We anticipate to complete analysis of the 6 month angiographic follow-up of all 100 patients by the time of the AHA2008. Conclusions: The HEALING-IIB study suggests that the EPC capture coronary stent in combination with statin therapy does not sufficiently impede stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it failed to stimulate CD34+ stem cell levels and did not improve the angiographic outcome of the bioengineered EPC capture stent.

scholarly journals Endothelial progenitor cells participation in cardiovascular and kidney diseases: a systematic review

2016 ◽  
Vol 63 (3) ◽  
Author(s):  
Jolanta Kiewisz ◽  
Monika M. Kaczmarek ◽  
Anna Pawlowska ◽  
Zbigniew Kmiec ◽  
Tomasz Stompor
Keyword(s):  
Cardiovascular Diseases ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Blood Cells ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Small Population ◽  
Endothelial Progenitor ◽  
Abundant Evidence ◽  
Macrophage Lineage

Endothelial progenitor cells (EPCs) represent a small population of blood cells (5-40 cells/mm3), with an ability to differentiate into endothelial cells that form the lining of the blood vessels and contribute to postnatal angiogenesis. Abundant evidence shows that recruitment of EPCs from the bone marrow, the monocyte/macrophage lineage and the organs facilitate the endothelial regeneration and repair. Changes in the number of EPCs were observed in both, chronic kidney and cardiovascular diseases. Thus, these cells were tested for usage in diagnosis and therapy. In this paper, we review the current knowledge on the EPC biology and contribution of these cells to the kidney and cardiovascular diseases.

Circulating endothelial progenitor cells correlate to stage in patients with invasive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 616-616
Author(s):  
R. Naik ◽  
D. Jin ◽  
E. Chuang ◽  
E. Gold ◽  
E. Tousimis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Research ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Invasive Breast Cancer ◽  
Peripheral Blood ◽  
De Novo ◽  
Rank Test ◽  
Tumor Biomarker ◽  
Endothelial Progenitor

616 Background: Tumor growth and metastasis is dependent on neo-angiogenesis. Both pre-existing and circulating vascular cells have been shown to contribute to the assembly of tumor neo-vessels in specific tumors. Mobilization of endothelial progenitor cells (EPCs) from the bone marrow constitutes a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be increased in certain malignant states. However, the role of circulating EPCs in breast cancer is largely unknown. Methods: We recruited twenty-five patients with biopsy-proven invasive breast cancer (BC) at Weill Cornell Breast Center to participate in a pilot study investigating the correlation of circulating EPCs to extent of disease and initiation of chemotherapy. For each patient, a baseline sample was drawn before systemic treatment, and for seventeen of those patients, a second sample was taken after the first round of chemotherapy. Levels of peripheral blood EPCs, as defined by co-expression of CD133 and VEGFR2, were quantified by flow cytometry. Results: BC patients with stage III & IV disease had statistically higher levels of circulating EPCs than did patients with stage I & II disease (median=165,000 EPCs/5×106MNCs vs. median=6,920 EPCs/5x106MNCs, respectively, p < 0.0001 by Wilcoxon rank-sum test). In addition, in late-stage patients, levels of EPCs demonstrated a statistically significant drop after initiation of chemotherapy (median=162,500 EPCs/5x106MNCs [pre] vs. median=117,500 EPCs/5x106MNCs [post], p = 0.01 by Wilcoxon signed-rank test). Conclusion: These results suggest that circulating EPCs may serve as a potential tumor biomarker in breast cancer and that EPCs may represent a plausible target for future therapeutic intervention. Supported in part by the Mentored Medical Student in Clinical Research Program (General Clinical Research Center/National Institutes of Health Grant M01RR00047), Madeline & Stephen Anbinder Clinical Scholar Award, and Anne Moore Breast Cancer Research Fund No significant financial relationships to disclose.

scholarly journals Lapine CD133+CD34+ endothelial progenitor cells for musculoskeletal research in preclinical animal trials

2020 ◽  
Author(s):  
Hitesh Chopra ◽  
Yuanyuan Han ◽  
Chengfei Zhang ◽  
Edmond Ho Nang Pow
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
De Novo ◽  
Functional Characterization ◽  
Seeding Density ◽  
Proliferative Potential ◽  
No Production ◽  
Endothelial Progenitor ◽  
Human Cd34

Abstract BackgroundValidated animal models form the cornerstone of in vivo clinical trials. Rabbits, for instance, have been widely used in musculoskeletal research, but there is a lack of knowledge regarding endothelial progenitor cells (EPCs) obtained from their peripheral blood (PB). Further, there is an ambiguity regarding the origin of EPCs in blood. The present study aimed to isolate and compare rabbit EPCs with human EPCs and explore the origin of EPCs in PB. MethodsMononuclear cells (MNCs) were isolated from the PB of rabbits and humans by density centrifugation. Different parameters, such as seeding density, type of medium, and technique (Depletion v/s Hills technique) were standardized for the emergence of EPCs. Homogenous rEPCs and hEPCs were isolated by double sorting with fluorescence-activated cell sorting (FACS) using CD34CD133 or CD34VEGFR-2 antibody. Expanded CD34+CD133+ EPCs from both rabbits and humans were compared using growth curve, acetylated low-density lipoprotein (acLDL) uptake, lectin binding, flow cytometry, immunofluorescence (IF), tubulogenic assay, and NO production. ResultsInitial seeding density of MNCs at 1 ́106 cells/cm2 with EGM-2MV supplemented with 5% FBS using depletion technique (40% as compared to 20% by Hill's technique) was found to be optimal for culturing EPCs. Further, depletion technique yielded cobblestone EPCs in 28% of rabbit samples as compared to 40% of human blood specimens in three different patterns blood-island like cell culture (central lEPCs and peripheral early EPCs), biphasic EPCs (early EPCs and late EPCs), and de novo EPCs (late EPCs only). Homogenous rEPCs and hEPCs were sorted using CD34+CD133+ and CD34+VEGFR-2+ antibody. Further, with FACS analysis, rCD34+CD133+EPCs were found to be one third (3%) as compared to human CD34+CD133+EPCs (12%). These CD34+CD133+ rEPCs/hEPCs were double-positive for acLDL uptake, ULEX binding, CD34, CD309, and CD31; whereas negative for CD133, CD14 and CD45. Also, EPCs from both species demonstrated functional characterization. ConclusionsrCD34+CD133+EPCs in general, were mostly similar to human CD34+CD133+EPCs in proliferative potential, functional characterization, and phenotypic identity. However, the rEPCs appeared to be larger, expressed higher phenotype expression, higher NO production, and had a significantly thicker junctional area, tube thickness, and longer tubule length (P<0.05).

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