scholarly journals CELL-FREE CONDITIONED MEDIA FROM ENDOTHELIAL PROGENITOR CELLS ENHANCES ENDOTHELIAL ANGIOGENESIS, MIGRATION AND SURVIVAL: PARACRINE IMPLICATIONS FOR CELL THERAPY IN PULMONARY ARTERIAL HYPERTENSION

2014 ◽  
Vol 30 (10) ◽  
pp. S156
Author(s):  
C. Suen ◽  
Y. Deng ◽  
D. Stewart
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Cell Therapy ◽  
Arterial Hypertension ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Conditioned Media ◽  
Endothelial Progenitor ◽  
Pulmonary Arterial

Abstract 332: Cell-Free Conditioned Media From Endothelial Progenitor Cells Enhance Endothelial Angiogenesis, Migration and Survival: Paracrine Implications for Cell Therapy in Pulmonary Arterial Hypertension

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Colin Suen ◽  
Yupu Deng ◽  
Duncan Stewart
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Conditioned Media ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Pulmonary Arterial

Background: Endothelial progenitor cells (EPCs) have been shown to be effective in the prevention of pulmonary arterial hypertension (PAH) in preclinical models. Our group has also demonstrated that xenotransplantation of human early EPCs in the rat monocrotaline (MCT) model prevented pulmonary arterial hypertension, despite the near complete loss of human cells from the lung after even 24 hours. Therefore, we hypothesize that the therapeutic effects of EPCs in PAH are mediated by a paracrine mechanism, which in turn, may enhance endothelial repair and integrity. Methods: EPCs were derived from human peripheral blood mononuclear cells obtained via leukapheresis by adherence to fibronectin and growth in endothelial growth medium (EGM-2MV). 24 hour conditioned medium from Day 6 EPCs (EPC-CM) was collected and concentrated by ultrafiltration prior to in vitro and in vivo studies. PAH was induced by a single intraperitoneal injection of (MCT) in nude athymic rats (150-200 g). EPC (5x106/kg) or EPC-CM from an equivalent number of cells were administered via jugular vein at day 3 after MCT and hemodynamics and echocardiography were assessed at day 24. Results: Incubation of human umbilical vein endothelial cells (ECs) with EPC-CM enhanced Matrigel capillary-like network formation by approximately 2-fold compared with serum-free media (p<0.05). EPC-CM increased migration in the scratch wound-healing assay compared to control media (4-fold, p<0.001). EPC-CM also significantly improved survival of HUVECs after serum deprivation (p<0.05) in a dose-dependent manner. Injection of EPCs resulted in decreased right ventricular systolic pressure (p<0.05) and improvement in pulmonary artery acceleration time (+28%, p<0.05). However, infusion of an equivalent amount of EPC-CM as well as a 10-fold increased dose of EPC-CM failed to prevent PAH. Conclusions: Therefore, EPC-CM enhanced in vitro EC angiogenesis, migration, and survival, consistent with potential of a paracrine mechanism. However, in an in vivo preclinical model, EPC conditioned media did not prevent PAH, suggesting that intact cells act through mechanisms that may involve cell-cell signaling.

scholarly journals Endothelial progenitor cells in pulmonary arterial hypertension

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Jeremy E Loehr ◽  
Eve Tremblay ◽  
Marie‐Renée Blanchet ◽  
Sébastien Bonnet ◽  
Steeve Provencher
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor ◽  
Pulmonary Arterial
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