215 - Placental Foxf1-expressing endothelial cells engraft into the pulmonary vasculature

Publication Number: 215.6230

Andreas Damianos, Phoenix Children's Hospital, Phoenix, AZ, United States; Guolun Wang, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Vladimir Ustiyan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Zicheng Deng, The university of arizina, Phoenix, AZ, United States; Bingqiang Wen, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, United States; Fatemeh Kohram, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, United States; Wen Gao, The University of Arizona, Phoenix, AZ, United States; Enhong Li, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, United States; Ying-Wei Lan, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, United States; Jonathan Do, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, United States; Xiaomei Xia, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, United States; Tamara Tilburgs, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Jerzy W. Stanek, Cincinnati Children's Hospital, Cincinnati, OH 45225, OH, United States; Tatiana Kalin, Phoenix Children's Hospital, phoenix, AZ, United States; Vladimir Kalinichenko, Phoenix Children's Hospital, Phoenix, AZ, United States

Background: Foxf1-expressing endothelial cells (Foxf1+ ECs) are a subtype of endothelial progenitor cells (EPCs) considered residents to the pulmonary vasculature. These cells restore the endothelium and are important benefactors and regulators of the pulmonary vascular niche in periods of neonatal lung injury. Their absence has been linked to alveolar capillary dysplasia (ACD) and they are found in decreased numbers in conditions such as Bronchopulmonary Dysplasia (BPD). Transplantation of these cells has great therapeutic potential and ameliorates the phenotypes in mouse models of ACD and BPD. However, these cells have limited bioavailability and the identification of other sources is warranted.

Objective: To identify Foxf1+ ECs in the placental tissues and compare their transcriptomic signature and function with their pulmonary counterparts.

Design/Methods: Murine placental tissues were investigated via immunohistochemistry (IHC), flow cytometry (FC), and correlated with human placentas for the presence of Foxf1+ ECs. Comparative transcriptomic analyses was conducted between lung- and placentally-derived Foxf1+ ECs. Engraftment assay was performed in a mouse genetic model of ACD.

Results: Foxf1+ ECs were identified in mouse placentas via IHC and FC. These cells comprise 28.8%±4 of the total placental EC population. Transcriptomic expression analyses revealed three distinct placental endothelial populations, one of which co-expresses Foxf1 and stem cell factor (Kit). This population was found to have similar transcriptional signature to the pulmonary counterparts. Next, we purified murine placental Foxf1+ ECs using transgenic mice expressing GFP-reporter knocked into the endogenous Foxf1+ gene locus. Transplantation of these cells into a model of ACD revealed their engraftment into the host’s pulmonary vasculature. The Foxf1+ ECs were also identified in human placentas and located in 80% of the chorionic vessels.

Conclusion(s): Foxf1+ EC populations has been previously described only in the pulmonary vasculature. With this study, we document the existence of a population in placental tissues that has similar transcriptomic expression with the pulmonary endothelial cells and is able to engraft into the pulmonary vasculature. These findings suggest that these cells may serve as an alternative source for progenitor-based cell therapy in the cases of BPD and ACD. Since placental tissues are commonly discarded, utilization of a readily available EPC pool can be extremely important in cases of auto-transplantation to at-risk populations.