Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia.
Late-outgrowth endothelial colony-forming cells (ECFCs), a type of circulating endothelial progenitor cell (EPC), may contribute to pulmonary angiogenesis during development. Cord blood ECFCs from preterm newborns proliferate more rapidly than term ECFCs but are more susceptible to the adverse effects of hyperoxia. Recent studies suggest that bone marrow-derived EPCs protect against experimental lung injury via paracrine mechanisms independent of vascular engraftment. To determine whether human umbilical cord blood ECFCs from preterm and term newborns have therapeutic benefit in experimental neonatal lung injury, we isolated cord blood ECFCs from full-term and preterm newborns and prepared ECFC-conditioned medium (CM) to test its therapeutic benefit on fetal pulmonary artery endothelial cell (PAEC) proliferation and function as well as alveolar type 2 (AT2) cell growth. PAECs and AT2 cells were isolated from late-gestation fetal sheep. Additionally, we administered both ECFCs and ECFC-CM to bleomycin-exposed newborn rats, an experimental model of bronchopulmonary dysplasia (BPD). Both term ECFC-CM and preterm ECFC-CM promoted cell growth and angiogenesis in vitro. However, when ECFC-CM was collected during exposure to mild hyperoxia, the benefit of preterm ECFC-CM was no longer observed. In the bleomycin model of BPD, treatment with ECFC-CM (or CM from mature EC) effectively decreased right ventricular hypertrophy but had no effect on alveolar septation. We conclude that term ECFC-CM is beneficial both in vitro and in experimental BPD. During oxidative stress, preterm ECFC-CM, but not term ECFC-CM, loses its benefit. The inability of term ECFC-CM to promote alveolarization may limit its therapeutic potential.
['Baker|Christopher D|CD|', 'Seedorf|Gregory J|GJ|', 'Wisniewski|Benjamin L|BL|', 'Black|Claudine P|CP|', 'Ryan|Sharon L|SL|', 'Balasubramaniam|Vivek|V|', 'Abman|Steven H|SH|']
D000818:Animals D000831:Animals, Newborn D000903:Antibiotics, Antineoplastic D001761:Bleomycin D015153:Blotting, Western D001997:Bronchopulmonary Dysplasia D049109:Cell Proliferation D002478:Cells, Cultured D017077:Culture Media, Conditioned D005260:Female D005312:Fetal Blood D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D018496:Hyperoxia D006976:Hypertension, Pulmonary D007124:Immunoenzyme Techniques D007231:Infant, Newborn D018919:Neovascularization, Physiologic D011650:Pulmonary Alveoli D011651:Pulmonary Artery D051381:Rats D017207:Rats, Sprague-Dawley
angiogenesis bronchopulmonary dysplasia endothelial progenitor cells conditioned medium pulmonary arterial hypertension