Faculty Opinions recommendation of Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants.

Author(s):  
Ole Skøtt
2006 ◽  
Vol 12 (2) ◽  
pp. 230-234 ◽  
Author(s):  
Dontscho Kerjaschki ◽  
Nicole Huttary ◽  
Ingrid Raab ◽  
Heinz Regele ◽  
Katalin Bojarski-Nagy ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
H Duckers ◽  
Yoshinobu Onuma ◽  
Edouard Benit ◽  
Robert J de Winter ◽  
William Wijns ◽  
...  

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.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 616-616
Author(s):  
R. Naik ◽  
D. Jin ◽  
E. Chuang ◽  
E. Gold ◽  
E. Tousimis ◽  
...  

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.


2016 ◽  
Vol 203 (3) ◽  
pp. 141-152 ◽  
Author(s):  
Anna Ratajska ◽  
Ewa Jankowska-Steifer ◽  
Elżbieta Czarnowska ◽  
Radosław Olkowski ◽  
Grzegorz Gula ◽  
...  

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.


2020 ◽  
Author(s):  
Hitesh Chopra ◽  
Yuanyuan Han ◽  
Chengfei Zhang ◽  
Edmond Ho Nang Pow

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).


2008 ◽  
Vol 294 (3) ◽  
pp. L419-L430 ◽  
Author(s):  
Diego F. Alvarez ◽  
Lan Huang ◽  
Judy A. King ◽  
M. Khair ElZarrad ◽  
Mervin C. Yoder ◽  
...  

Endothelial progenitor cells (EPCs) have been isolated postnatally from bone marrow, blood, and both the intima and adventitia of conduit vessels. However, it is unknown whether EPCs can be isolated from the lung microcirculation. Thus we sought to determine whether the microvasculature possesses EPCs capable of de novo vasculogenesis. Rat pulmonary artery (PAEC) and microvascular (PMVEC) endothelial cells were isolated and selected by using a single-cell clonogenic assay. Whereas the majority of PAECs (∼60%) were fully differentiated, the majority of PMVECs (∼75%) divided, with ∼50% of the single cells giving rise to large colonies (>2,000 cells/colony). These highly proliferative cells exhibited the capacity to reconstitute the entire proliferative hierarchy of PMVECs, unveiling the existence of resident microvascular endothelial progenitor cells (RMEPCs). RMEPCs expressed endothelial cell markers (CD31, CD144, endothelial nitric oxide synthase, and von Willenbrand factor) and progenitor cell antigens (CD34 and CD309) but did not express the leukocyte marker CD45. Consistent with their origin, RMEPCs interacted with Griffonia simplicifolia and displayed restrictive barrier properties. In vitro and in vivo Matrigel assays revealed that RMEPCs possess vasculogenic capacity, forming ultrastructurally normal de novo vessels. Thus the pulmonary microcirculation is enriched with EPCs that display vasculogenic competence while maintaining functional endothelial microvascular specificity.


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