A106-07 Placental Endothelial Cells as Therapeutics in a Hyperoxic Model of Bronchopulmonary Dysplasia

Intro Bronchopulmonary dysplasia (BPD) is a debilitating condition of the extreme preterm infant. Once established, it carries increased morbidity and mortality. It is the result of alveolar developmental arrest associated with vascular rarefaction and remodeling. Improving a maldeveloped vascular and alveolar tree is very difficult, and current therapeutics have limited efficacy. Stem cells are a promising new avenue. FOXF1+ endothelial cells (ECs) is an endothelial progenitor population with demonstrated angiogenic and vasculogenic potential after damage, however their bioavailability is limited. We identified that placentas harbour ECs that express FOXF1 and/or stem cell factor receptor(cKit) which are progenitor markers. These cells have phenotypic similarities to the pulmonary EPCs. Herein we explore the use of placental(PL) EPCs as therapeutics in models of BPD. Objectives To evaluate whether PL ECs ameliorate the phenotype cause by hyperoxic exposure in a model of BPD. Methods The E16.5 murine PL endothelium was investigated via immunohistochemistry, flow cytometry (FC). Viable single-cell PL ECs were transplanted at P14 in a murine BPD model (generated via hyperoxic exposure from P0-P14) via intravenous administration and phenotypic recovery was assessed a week later. Results E16.5 PL ECs (CD31+,CD45-) compromise 12.2%±4 of the live isolated cells. Interogated for FOXF1 and cKIT expression, we identified FOXF1+, cKit+ECs that compromize 3%±0.4 of the total ECs. FOXF1+cKit- ECs at 28.8%±4 and FOXF1-,cKit+ECs that compromise 20%±2 of the isolated live ECs. To assess therapeutic efficacy of the PL ECs; we administered live 105 harvested ECs originating from transgenic mice that express tdTomato into the hyperoxic exposed mice (HYP). Phenotypic recovery was assessed at P21. ECs isolated from the HYP- treated mice displayed increase in endothelial populations compared to HYP and Room Air(RA) groups. (40.9%±15* vs 8.5%±3 vs 11.1%±1,*: HYP-treated vs HYP & HYP-treated vs RA, p < 0.05 N = 6-10/group). Identification of expressed dtTomato in the host’s lung suggests engraftment (very small percentage 0.1±0.06). Phenotypic recovery was assessed by histology and it was found that HYP-treated mice had alveolar airspace similar to RA (61.1%±4.5 vs 61.9%±5.5, N = 6-10/group). Discussion PL ECs display progenitor capabilities as they engraft into the pulmonary vasculature and seem to lead to phenotypic improvement in a mouse model of Bronchopulmonary Dysplasia. These preliminary results are reassuring; however further studies need to be performed. If subsequent studies confirm our findings, then placental endothelial cells may be a population of choice for pulmonary vascular conditions of maldevelopment such as BPD.